The clinical and cost effectiveness of behavioural therapy for interepisode bipolar symptoms (STABILISE): A randomised, controlled feasibility trial.

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Kim Wright, Fiona C Warren, Sandra Bucci, Barnaby Dunn, Steven Jones, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5223139/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Pilot and Feasibility Studies → Version 1 posted 5 You are reading this latest preprint version Abstract Background: In between episodes of (hypo) mania and major depression, people with bipolar disorder can experience ongoing low mood or mood instability, and these may also be present as part of cyclothymic disorder. This is a phase II evaluation of an adapted form of behavioural therapy (STABILISE) for inter-episode bipolar symptoms. The study aims to establish the feasibility and acceptability of the therapy and research procedures, including an economic component, to inform a future definitive trial. Methods: Patients will be randomised 1:1 to either Treatment as Usual (control arm) or Treatment as Usual plus STABILISE intervention (intervention arm). Follow up points will be at 14, 30 and 52 weeks post eligibility confirmation, with 30 weeks as the primary end point. We aim to recruit 60 individuals meeting diagnostic criteria for a Bipolar Spectrum Disorder, and reporting ongoing bipolar symptoms (low mood or mood instability) outside of a manic or severe depressive episode. Feasibility and acceptability will be examined through recruitment and retention rates, completion rates for the candidate primary outcome measures (PHQ9, ALS-SF, QoL.BD and BRQ) and feedback from participants on their experience of study participation and therapy. Proceeding to a definitive trial will be indicated if the following criteria are met: i) trial participation is deemed, or can be made, sufficiently safe; ii) recruitment rate indicates that larger-scale recruitment would be feasible (recruitment rate of at least two participants per month within at least one site, with mitigation plan if overall target sample size not met); iii) for candidate primary outcome measure follow up data is available at 30 weeks from at least 75% of participants, or from between 55 and 74% with clear plan for improvement. Discussion: This study is a randomised, controlled feasibility trial that builds on an initial case series of the STABILISE approach. The findings will be used to establish whether a future, definitive trial is feasible and to refine the research procedures and therapy protocol. Trial Registration : ISRCTN18207465. Registered 13 th March 2024, https://www.isrctn.com/ISRCTN18207465. Protocol version: 1.2 30.8.24 Bipolar Disorder Cyclothymic Disorder behavioural therapy psychological therapy interepisode symptoms Figures Figure 1 Background Bipolar spectrum disorders (Bipolar I or II Disorder, Cyclothymic Disorder) result in substantial personal and societal costs and affect around 1 in 20 people across their lifetime [ 1 , 2 ]. In addition to major episodes of depression or mania, people with bipolar spectrum disorders can experience ongoing bipolar symptoms (inter-episode Bipolar symptoms (IEBS)). With IEBS, depressive symptoms tend to be more frequent relative to hypomanic symptoms [ 3 ] and instability of mood is common [ 4 ]. Interventions are needed for IEBS for three reasons. First, they are common: ongoing bipolar symptoms in the form of subclinical low mood or mood instability are experienced by up to half of those with Bipolar I or II Disorder who are not in a major episode [ 5 ], and on average people with bipolar I or II disorder spend around twice as long experiencing residual symptoms as they spend in acute episodes [ 3 ]. Second, they are associated with significant distress and impairment, including increased psychiatric comorbidity and poorer functioning [ 4 – 9 ]. Third, the ongoing mood instability that constitutes cyclothymic disorder is associated with risk of developing full depression and mania [ 10 ], which can be costly to the health service and the wider society, and costly to patients and families. Indeed, in a UK study, for each unit increase in average levels of depressive or manic symptoms there was an increase in societal costs of 7% and 11%, respectively [ 2 ]. Despite the impact of IEBS studies evaluating approaches to helping people with this disabling presentation are scarce. Furthermore whilst some have examined the effects of pharmacological agents on residual symptoms [ 11 ], relatively few consider their impact on mood instability. Psychological therapies for individuals with bipolar disorder are valued by service users, and are recommended within various national treatment guidelines, yet the extant literature does not provide direct guidance on the optimal psychological treatment for people with IEBS, with studies tending to focus on relapse prevention or alleviation of acute depression as the primary target of therapy [ 12 ] or specifically upon cyclothymic disorder [ 13 ]. Thus, we do not currently have a psychological treatment that seeks to address the common ongoing mood symptoms (subclinical low mood and mood instability) that people with bipolar disorder (BD) or cyclothymic disorder (CD) present with, nor a therapy that has been tested across the bipolar spectrum with respect to these issues. Our approach (STABILISE: Study of Therapy for Bipolar Interepisode Symptoms) brings together two behavioural therapies that are commonly used and effective with related populations to address key therapy targets also relevant to IEBS: reduction of depressive symptoms through supporting meaningful behaviours, and management of problematic affective instability. The resulting therapy is designed to support people with BP or CD in managing ongoing difficulties with low mood or mood instability, including the impact of these on everyday life. Behavioural Activation (BA) is used extensively in the treatment of acute unipolar depression [ 14 , 15 ]. It is informed by the behavioural theory of depression whereby depression is hypothesised to be maintained by a reduction in access to positive reinforcement from the person’s context, and a subsequent increase in “avoidance” behaviours that function to reduce negative affect rather than to approach valued goals. Correspondingly BA involves supporting the person to access previous and new sources of reward through scheduling goal and value-consistent activities into the week and learning or re-accessing skills for managing barriers to engaging fully in these activities. BA is often considered to represent a parsimonious and relatively straightforward approach to disseminate, potentially reducing training costs and broadening the range of health professionals who may be able to deliver it [ 16 ]. Two reports of case series data on its use in people with acute bipolar depression [ 17 , 18 ] describe high acceptability rates, no safety concerns and encouraging patterns of change on clinical outcome measures. Dialectical behaviour therapy (DBT) is a form of behavioural therapy originally developed for women with borderline or emotionally unstable personality disorder [ 19 , 20 ] and later applied across genders and across multiple problem areas. It is based upon the biosocial theory which posits that emotion dysregulation is the outcome of an interaction between an emotionally sensitive temperament and an early environment that invalidates their emotional responses. DBT teaches the person skills for recognising and responding to emotional states, and for managing the situations that can trigger these responses. A behavioural framework is used to understand the interaction between the person and their context, and the therapist stance models appropriate validation of emotion and a dialectical outlook, whereby it is acknowledged that two seemingly contradictory accounts can both be true (e.g. “I am an okay person and I can adapt my behaviours in this context to get a better outcome for myself and others”. The full DBT programme includes group skills training, individual therapy sessions, skills coaching outside of sessions, structuring the environment and group consultation between therapists; however, partial versions of DBT, often called DBT-informed interventions, have been developed. DBT, including DBT-informed interventions, has been tested for a range of patient groups, including people without a diagnosis of personality disorder, where emotional dysregulation plays a role in the presenting issues [ 21 – 23 ]. It has found to be effective in reducing substance use and self-harm (both being behaviours that are often used by individuals to cope with intense, seemingly unmanageable affect) and problematic anger. A small number of case series and feasibility studies have explored DBT-informed interventions for people with bipolar disorder, with promising outcomes in terms of acceptability and likely clinical benefit; these vary in the extent to which they adhere to the traditional DBT programme versus include concepts and techniques influenced by DBT or other emotion regulation programmes [ 24 ]. In addition, except for one study [ 25 ], these studies do not focus specifically on inter-episode symptoms or include individuals with cyclothymic disorder. With input from people with lived experience of bipolar disorder, and family members, we integrated concepts and techniques from DBT within a BA protocol used previously with individuals with bipolar depression [ 18 ]. An initial examination of the safety and acceptability of the resulting therapy was conducted within in a case series of 12 individuals with BD or CD and ongoing low mood or mood instability. At the time of writing, the acute treatment phase of the case series is complete and pre-determined rules to allow progression to the next phase of evaluation, a randomised controlled feasibility trial, have been met (no serious concerns about therapy safety; instances of reliable improvement exceed instances of reliable deterioration). The protocol for this feasibility trial is presented here. The overall aim of this study is to determine the likely feasibility, acceptability and safety of the research procedures, including the therapy protocol, to design a future definitive randomised trial to determine the clinical and cost effectiveness of the STABILISE therapy programme. Objectives i) To inform the recruitment and timeline of a future fully-powered trial, by informing estimates of the number of participants who will need to be identified, approached, consented, randomised and who are likely to complete outcome assessments; ii) To refine future trial procedures by establishing the acceptability and experience of the trial process to participants. This includes acceptability and experience of randomisation and outcome measures; iii) To inform selection of the optimal primary outcome measure in a future trial by assessing the performance of selected candidate primary outcome measures with respect to level of acceptability to participants and participant-perceived relevance and value. Although not powered to detect a significant between group mean difference, we will scrutinise between group mean differences for each outcome measure, as well as relative rates of reliable improvement and deterioration, to assess sensitivity of the measure to the impact of the intervention. iv) To inform estimation of sample size for a future trial by measuring data completeness at follow up (participant attrition) and standard deviation of the likely primary outcome measure (to compare to reports in published literature). v) To characterise the comparator condition, treatment as usual, across individuals and sites. vi) To further explore the safety and acceptability of the treatment and, based on input from trial participants and clinicians, to further refine and develop the treatment manual and the procedures for training, supervising and assessing the competence of trial therapists. vii) To demonstrate feasibility outside of the lead site by including a second site. vii) To demonstrate feasibility outside of the lead site by including a second site. viii) To estimate the cost of the intervention. ix) To assess the feasibility of collecting health care resource utilisation data and health-related quality of life data using the EQ-5D-5L [26]. x) To explore the feasibility of collecting momentary assessment (experience sampling) data at three time points (5 times per day, for 10 days, at each timepoint): the ultimate purpose of collecting these data in a future larger trial is to estimate mood instability and to examine process of change. The criteria for progression to definitive trial are given in Table 1, presented in accordance with the framework proposed by Avery and colleagues [27]. Table 1 Criteria for progression to a definitive trial Red Amber Green Overall safety of intervention and trial procedures as determined by TSC and sponsor a Cannot be made sufficiently safe for use in a definitive trial Can be made sufficiently safe following modification Sufficiently safe for use in a definitive trial Mean recruitment rate per site over 15 months < 2 participants per month at both sites < 2 participants per month at one site and target sample size not reached, with clear plan for improvement ≥ 2 participants at both sites OR < 2 participants at one site but overall target sample size reached b Outcome measure completion at 30-week follow-up point (completion of candidate primary outcome measure at primary end point) < 55% of participants Between ≥ 55 and < 75% of participants, with clear plan for improvement ≥ 75% of participants Level of completion of intervention (defined as attending at least 6 therapy sessions) c < 50% of participants 50–89% of participants, with clear plan for improvement ≥ 90% of participants Note . Red: Do not progress to the main trial (unless TSC agree exceptional circumstances and a mitigation plan is present); Amber: Progress if action plan to mitigate problems can be determined and agreed with the Trial Steering Committee (TSC); Green: Progress directly to the main trial. a Subsequent to reviewing information on adverse and serious adverse events arising during the trial. b To allow for a situation in which recruitment systems require a lead-in period at a site before becoming optimized, and this optimization period can then be accounted for in planning for a definitive trial. c Information will be collected on reasons for discontinuation to inform plan for enhancing retention in intervention and / or refinement of the estimand for a definitive trial [ 28 ]. [Table 1 about here] Methods This feasibility study protocol is reported according to the SPIRIT 2013 statement (see additional file 1 for a completed SPIRIT checklist). Design This feasibility study has a two-arm randomised parallel controlled trial design. Participants will be randomised on a 1:1 ratio to Treatment as Usual (TAU) only (control arm) or TAU plus STABILISE programme (intervention arm). Outcome measures will be completed at baseline and at three follow-up points: 14, 30 and 52 weeks post study entry. We have selected 30 weeks as the primary end point to allow this to be immediately following the intervention period. The study takes a mixed-method approach whereby evaluation of therapy acceptability and potential impact is explored both qualitatively and quantitatively. Setting and Participants The trial will be conducted across two sites in the U.K. (an NHS mental health Trust, and a specialist NHS outpatient psychological therapies service based at the University of Exeter) with participants allowed to be recruited from primary care services, secondary care mental health services and via self-referral. For details of study sites please see: https://www.isrctn.com/ISRCTN18207465. Eligible participants will be aged 18 or over with a diagnosis of Bipolar Disorder (I,II, Other Specified Bipolar Disorder) or Cyclothymic Disorder, according to DSM-V[29] criteria assessed using the Structured Clinical Interview for DSM-V (SCID-5 [30]). Participants must report either current bipolar mood instability, defined as a score of at least 1.3 on the depression-elation subscale of the short form Affective Lability Scale (ALS [31]), or presence of at least mild depressive symptoms, defined as a score of at least 5 on the 9-item version of the Patient Health Questionnaire (PHQ-9 [32]). They must also be willing to engage in psychological therapy that focusses primarily on psychological work addressing ongoing bipolar symptoms or their impact on functioning, and must be able to attend regular therapy sessions. Participants must have sufficient competency in English such that study measures can be completed without the need for translation (to preserve the measure properties), have completed the intake measures, and be registered with a General Practice in the study site catchment area. Participants will not be included if they are currently experiencing a manic episode (assessed using the SCID-5) or severe major depressive episode (assessed using the SCID-5; the Hamilton Depression Rating Scale [33], an established, validated measure of current depression symptoms, will be used with participants who meet criteria for a current depressive episode to establish severity). We will not include participants with current substance dependence according to The International Classification of Diseases, 11 th revision (ICD-11 [34]) criteria; ICD-11 rather than DSM-V criteria are used to permit assessment of substance dependence rather than the broader construct of substance use disorder. Participants receiving other psychological therapy for bipolar disorder or who present a risk of harm to themselves or others that cannot be safely managed in a community outpatient setting will not be included. Medication status will not serve as an exclusion criterion but will be recorded. In both conditions participants will continue to be able to access routine care. Sample Size A total of 60 individuals will be recruited (target n=30 in Devon, and n=30 in Avon & Wiltshire). A sample size of 60 participants allows estimation of loss to follow-up within +/- 12 percentage points, assuming 20% attrition, and is sufficient to estimate the standard deviation in the candidate primary outcome measures [35,36]. Randomisation, Concealment of Allocation, and Blinding Participants eligible for the study will be randomised on a 1:1 ratio (with minimisation by trial site and medication status [currently prescribed medication for depression or Bipolar Disorder versus not prescribed such medication]) to Treatment as Usual (TAU) [control arm] or Treatment as Usual plus STABILISE programme (TAU + STABILISE) [intervention arm]. Allocation concealment during the randomisation process will be achieved through use of a validated password protected online randomisation tool programmed and hosted by the Exeter Clinical Trials Unit. The first six participants will be allocated using simple randomisation and then the minimisation procedure will commence, maintaining a stochastic element to the algorithm to allow concealment to be maintained. The minimisation algorithm will take account of the allocations of the first six participants. Participants will be enrolled into the randomisation system and informed of their allocation by an unblinded researcher. Given the nature of the intervention, blinding of participants to allocation is not possible. Follow-up assessments will be conducted by separate researchers who are unaware of the participant’s allocation. At follow-up, outcome assessors researchers will be instructed to maintain blinding by reminding participants not to reveal their allocation during the contact. Outcome assessors will be asked to indicate at follow-up which treatment they believe the participants received, allowing us to test blinding status and analyse any correlation with outcome. The outcome assessors’ blind will be maintained as far as possible; they will be deliberately unblinded only in exceptional circumstances where knowledge of the treatment arm is deemed essential to their management of the participant (e.g. certain Serious Adverse Events). Instances of deliberate or accidental un-blinding will be recorded; future data collection from that participant will be carried out by a member of the team who remains blinded. An unblinded researcher will collect data from participants that pertains to their allocation (qualitative and quantitative feedback about their experience of the study and of the therapy). All other members of the study team will be unblinded other than those performing statistical analyses on the data (health economist and statistician). Statistical and economic analyses will be performed by a statistician and health economists who are blinded to participant allocations. Recruitment Participants will be identified from local NHS services including but not limited to primary care psychological therapies services, General Practices, secondary care mental health teams, early intervention services and secondary care psychological therapies services. In addition, advertisements for the study will be placed in healthcare settings, public places and distributed through traditional and social media, and third sector organisations. Potential participants who are interested in the study will be given the choice of contacting the researchers directly by telephone, email or post, or completing a “permission to contact” form which can be passed to the research team by their clinician or sent directly to the study team by the participant. After a potential participant contacts or is referred to the study, a member of the research team will answer any initial questions and have an initial discussion about the study if the person wishes. Following receipt from the participant of a completed form gaining their consent for contact and an initial telephone screening call (“permission to contact” form), the researcher will arrange a time to complete this with the participant. In the screening call the researcher will go through the inclusion and exclusion criteria with the participant, to give an indication of the likelihood that the participant will be eligible. Those likely to be eligible and willing to continue will be invited to the intake appointment. At the appointment the researchers will take written consent if the participant wishes to proceed and conduct the eligibility assessment. If the potential participant is eligible to partake in the study, is fully informed and has consented to participate, then they will be enrolled into the study. Participants will be offered an honorarium of £20 for their participation at four points in the study: the intake assessment and the 14,30 and 52 week follow-up points. Trial Intervention Using an approach informed by experience-based co-design [37], the STABILISE therapy programme was developed and refined through a series of workshops and other communications with patients and supporters, as well as input from therapists familiar with the component therapies. STABILISE seeks to incorporate emotion regulation strategies into a behavioural approach that seeks to promote re-engagement with valued activities and meaningful routine. Specifically, STABILISE recognises that instability in behaviours and affect in IEBS are related, and aims to help participants find a balanced, sustainable pattern of activity that enables them to live well within their situation, to support them to change their situation where possible and needed, and to make changes to patterns of behaviour that lead to problems or distress. This typically entails reducing mood-driven behaviour and increasing behaviours guided by the person’s values, plans or goals. These principles apply equally to depressed versus hypomanic states. Recognising that people with bipolar disorder have often experienced many years of threatening, uncontrollable shifts in affect, energy and motivation, STABILISE draws upon several key principles of DBT including an emphasis on validation of emotional experiences and a dialectical stance, balancing acceptance and change. It also incorporates, within the behavioural framework, techniques and ideas from DBT and other therapies that target emotion regulation. The intervention consists of up to 20 individual therapy sessions (plus up to 2 initial assessment sessions) of behavioural therapy, delivered up to 7 months (30 weeks). Therapy ends after 20 sessions or 7 months, whichever is sooner, and participants can choose to space sessions out over more than a week if they wish or to take a short break from therapy. Sessions are an hour long as default but with the option for participants to agree shorter or longer (up to 75 minute) session duration if needed. This is followed by a period of consolidation whereby participants can opt to see the therapist up to 3 times up until 12 months after starting therapy. All sessions will be audio-recorded (where participants consent to this) to allow for supervision and the refinement of a therapy adherence and competence measure. Therapy will be delivered by at least three therapists with an existing training in cognitive behavioural, behavioural or dialectical behavioural therapy and experience of working with people with mood disorders. Therapists new to delivering the intervention will receive a 3-day training programme and all therapists will receive supervision every 1-2 weeks from the therapy developer or a STABILISE senior therapist whilst delivering therapy. Therapy will be delivered face-to-face, online or by phone according to participant preference and what is feasible; local NHS service protocols will be followed in terms of telephone and online platform use. Face-to-face therapy will by default be delivered in the treatment centre; however, in keeping with the ethos of the approach (patient-centred, flexible, contextual and experiential) therapy sessions may take place outside of the centre if the participant wishes and it is appropriate and safe to do so. This may include practising activities together (e.g. visiting a shop) or sessions within the person’s home. Participants will complete the Beck Depression Inventory (BDI) [38] and Altman Scale for Rating Mania (ASRM) [39] prior to each session and the scores used to inform their care, as well as forming part of the research data collected. It is anticipated that changes to the therapy protocol during the feasibility trial will be minor (i.e. will concern including or excluding specific techniques, or the wording and presentation of therapy materials, rather than the underpinning principles, therapeutic approach and overall structure). Changes to the therapy protocol will be timestamped allowing identification of which participants received which version. The comparison arm in this trial is TAU. This was chosen because of the absence of a “gold standard” therapy for inter-episode symptoms against which the novel therapy can be benchmarked. To characterise the content of TAU across trial sites, we will collect data on health services used by participants. There will be no restriction on the content of TAU, other than as part of the exclusion criteria for study entry whereby participants must not currently be receiving psychological therapy for bipolar disorder. Outcomes As this is a feasibility trial, the primary outcomes relate to the key feasibility objectives. Objective 1 is to inform the recruitment and timeline of a future fully-powered trial. This will be evaluated using rates of recruitment from both sites (number of participants randomised per month), presented for each site and for both sites combined. Objective 2 is to refine future trial procedures by establishing the acceptability and experience of the trial process to participants, including randomisation and completion of outcome measures. This will be evaluated by examining outcome measure completion rates including health economics measures, attrition across the two arms, and quantitative and qualitative acceptability data from participants. Descriptive statistics will be presented including within a CONSORT diagram showing participant flow through the study, including number expressing an interest, completing a screening call, attending intake assessment, giving informed consent, being randomised, and completion of each follow-up point. More detailed descriptive statistics showing completion of each measure at each follow-up point will be presented in tabular form. Objective 3 is to determine the optimal primary outcome measure in a future trial. This will be achieved by examining per-measure completion rates, participant feedback on measures, participant rankings of importance, likely sensitivity to change, and presence of an established minimally important clinical difference value. At this stage, candidate future primary outcome measures include the PHQ9 [32], ALS-SF [31], brief Quality of Life in Bipolar Disorder Scale (QoL.BD [40]) and Bipolar Recovery Questionnaire (BRQ [41]). Completion rates for each measure will be presented at each time point; participant feedback on measures will be analysed qualitatively. Participant rankings of these four clinical outcome domains plus two additional potential secondary outcomes domains (anxiety and mania symptoms, measured by the Generalised Anxiety Disorder Questionnaire (GAD-7 [42]) and Bech Rating of Mania Scale (BRMS [43]) respectively), will be used to provide information on their value to participants: for each domain mean (SD) rank will be presented, where lower score equals higher rank, as well as number (%) of participants selecting each domain as first or second highest-ranked. Rankings will be gathered as part of an embedded study piloting three methods for establishing patient prioritisation of outcomes. In each method participants are asked to indicate the relative importance of change on each of the six outcome areas. For further details of the methods used please contact the corresponding author. To examine sensitivity of the measures to the impact of the intervention, between group mean differences will be calculated (with 95% confidence intervals), as will rates of reliable change [44] on the measures (reliable improvement, reliable deterioration). The information above will be considered within a stakeholder consensus meeting to agree the optimal primary (or co-primary) outcome measure(s) for a future definitive trial, with the ultimate decision made by the CI. Objective 4 is to inform estimation of sample size for a future trial. This will be evaluated by examining data completeness at follow up (participant attrition) as described for objectives 2 and 3, and standard deviation of candidate primary outcome measures (to compare with reports in published literature). Objective 5 is to characterise treatment as usual across individuals and sites. Data on treatment as usual will be presented descriptively based on health economic data collected at intake and at each follow up point. Objective 6 is to further assess the safety and acceptability of the treatment and, based on input from trial participants and clinicians, to further refine and develop the treatment manual and the procedures for training, supervising and assessing the competence of trial therapists. With respect to safety the number of adverse events (AEs) and serious adverse events (SAEs) will be reported descriptively for each treatment group using an As Treated approach, whereby participants will be reported according to treatment actually received, irrespective of group allocation. We will also report the number and percentage of participants experiencing at least one SAE, as well as between group comparisons of number of individuals experiencing an SAE using risk difference and odds ratio with 95% confidence intervals. Acknowledging that AEs and SAEs are more likely to be reported by those in the STABILISE + TAU arm because of regular contacts with their therapist, we will particularly attend to the outcome of between group comparisons of study-related versus unrelated events. Safety will also be assessed by examining rates of reliable deterioration at 30 weeks (number of participants showing reliable deterioration in both arms). With respect to acceptability this will be evaluated by examining therapy uptake and completion rates: number of participants entering and completing therapy, mean (SD) number of sessions attended and minimum and maximum. It will also be assessed by evaluating quantitative and qualitative feedback from participants and therapists: mean (SD) and minimum and maximum of quantitative ratings on acceptability items; and thematic analysis of participant feedback. The inter-rater reliability of the therapy competence measure will be assessed by two raters independently assessing the same 51 recordings of therapy sessions and their scores being used to calculate the intraclass correlation coefficient using a two-way random effects model, for both consistency and absolute agreement (n=51 allows estimation of ICC of 0.8 with 95% CI of 0.7-0.9). Objective 7 is to demonstrate feasibility outside of the lead site by including a second site. This will be evaluated by comparing rates of recruitment and retention across the two sites. Objective 8 is to identify, measure and value the cost components for delivering the intervention. These costs will include any necessary training and materials, as well as staff costs and supervision if necessary. It will take into consideration whether the intervention was delivered face-to-face, online or by phone. Objective 9 is to assess the feasibility of collecting health care resource utilisation data and health-related quality of life data using the EQ-5D-5L for obtaining utilities and estimating Quality-Adjusted Life Years (QALYs) at all timepoints. It will investigate the pattern of missingness as well as identifying which are the key cost drivers on resource utilisation. Objective 10 is to examine the feasibility of collecting momentary assessment data and baseline, 14 and 30 weeks: this will be addressed by examining rates and pattern of missingness as well as through participant report. Measures Demographic information At the baseline eligibility assessment demographic information ( age, gender, ethnicity, perceived financial status, sexual orientation) will be collected. Patient reported clinical outcome measures In addition to the PHQ-9 and ALS the following clinical outcome measures will be completed at baseline, 14, 30 and 52 week follow-up: BRMS, an 11-item observer-rated scale measuring level of current mania symptoms; QoLBD, a 12-item self-report measure of disorder-specific quality of life; GAD-7, a 7-item self-report measure of anxiety symptoms; BRQ, a 36-item self-report measure of sense of personal recovery; Life chart self-report, a self-report of number and duration of depressive and manic episodes in the period since last assessment (completed at 14, 30 and 52 week follow-up points only), completed with the support of the researcher; Health Economics Questionnaire (HEQ [45]) – self-report of health economic variables (employment, healthcare resource use) over past 6 months (at intake) or since last contact (at follow up assessments); EQ-5D-5L – a 5-item self-report measure of health-related quality of life, for obtaining utility values for estimating QALYs.. At this stage, candidate future primary outcome measures include the PHQ9, ALS, QoL.BD and BRQ. Quantitative process measures The theoretical model underpinning the therapy hypothesises that mood related difficulties are maintained, at least in part, by individuals responding impulsively to intense mood states, and some of these responses further affecting mood as well as contributing to difficulties in everyday life. In order to test this hypothesis in a future, larger trial we plan to use the following self-report measures, which are included in the current study, to assess the acceptability of doing so:Positive and Negative Urgency Scales (PU & NU [46]), two 4-item scales measuring impulsive responding to positive and negative mood; Behavioural Activation in Depression Scale – Short Form (BADS-SF[47]), a 9-item scale measuring behavioural avoidance versus approach within low mood (avoidance being a form of impulsive response to negative affect). As another means of assessing the process of change within therapy as part of a large, future trial we plan to measure mood and activity repeatedly to allow us to look at the inter-relationships between these. In the current study we plan to gather information on the feasibility and acceptability of collecting these data, having initially tested this method within our case series. Participants will be invited to report on their current mood and activity 5 times per day for 10 days via a purpose-built web application (momentary assessment block). These momentary assessment blocks will take place on three occasions: for 10 days following the intake assessment, for 10 days at 14 weeks post randomisation, and for 10 days following the 30-week follow-up point. Additional measures At the 30-week follow-up point, participants will complete a feedback questionnaire within which they will be asked to rate (on a scale from 1-4) their satisfaction with the therapy, how acceptable it was and the likelihood they would recommend it to a friend (for those in the intervention arm), and their overall satisfaction with the research element of the therapy (both arms), and also to give written comment on their answers to each questions and any general comments on the therapy or research. A brief feedback questionnaire will be sent to those exiting the study early, at the point they exit, if they have indicated they would be willing to complete this. To monitor and evaluate intervention and study safety an ‘Asking about adverse events’ form will be completed following the intake assessment (a researcher will check on participants’ wellbeing within a week of the intake assessment), and at the 14-, 30- and 52- week follow-up points. Members of the research team will also follow up with participants in relation to any potential adverse events mentioned in ad-hoc communications, therapy contacts or via HEQ completion. Participants will be invited to rank outcome measures according to which they would most wish to experience change upon. Rankings will be conducted at baseline, and at the 30-week follow-up point. Participants will be asked about their concordance with their prescribed psychiatric medication using the single, overall compliance question from the Brief Adherence Rating Scale (BARS [48]) at intake, 14 and 30 weeks. Qualitative interview At 30 weeks (patient participants) and at the end of the trial (therapists) there will be audio-recorded qualitative interviews of approximately 60 minutes conducted by one of the research team exploring experiences of the therapy. Fifteen participants in the intervention arm, purposively sampled to span diversity in terms of demographic characteristics and outcome in terms of therapy attendance, will be interviewed. All therapists who have delivered at least one therapy session as part of the study will be invited to be interviewed. The interview will allow participants / therapists to describe their views in detail. The interview will be informed by the topic areas highlighted in process evaluation guidance [49], namely fidelity and quality of intervention implementation, mechanisms of change and impact of context. Specifically, it will ask about how participants / therapists found the therapy, any perceived effects of the therapy, aspects that were helpful / unhelpful, and views on the length and delivery format of the treatment and the feasibility/acceptability of both the intervention and the outcome measurement (for participants). It will also ask about experienced process of change, including questions on hypothesised mechanisms but also leaving space for these to arise inductively from reports, as well as participants’ experiences of the impact of the context in which they received the intervention (their personal / social context, and the healthcare context). The interviews will follow a topic guide, but with flexibility to adapt this based on the answers given. Data collection forms will be available on request from the Chief Investigator following completion of the trial. Procedure Informed consent will be taken prior to or at commencement of the eligibility assessment by a member of the study team; consent will be re-affirmed verbally prior to qualitative interviews. Following the initial eligibility assessment and completion of baseline measures participants will be randomised to either STABILISE plus TAU, or TAU. Those allocated to the intervention arm will commence treatment approximately 2 weeks after being deemed eligible. Assessments at 14, 30 and 52 weeks will involve participants completing self-report measures either online or on paper, according to their preference, as well as speaking to a member of the research team (online, by telephone or in person) to complete the measures that require contemporaneous researcher involvement. A default procedure will be followed in cases where participants do not respond to requests to complete measures, with the procedure being tailored in accordance with individual patient preferences, as discussed following acceptance to the study. Figure 1 displays the measures completed at each time point. Data Analysis Statistical analyses Given the feasibility design, data analysis will focus on a descriptive analysis of the feasibility objectives of the study. Participant characteristics at baseline will be reported descriptively for each treatment group, using mean (SD) for continuous variables, and percentages for categorical variables. Outcome measures will be reported descriptively for each treatment group at baseline and at each post-randomisation follow-up, i.e. 14, 30 and 52 weeks. For 30- and 52-week follow-up data, the between group mean differences for continuous variables (intervention minus control group) will be reported with a 95% CI. Given the feasibility nature of the trial, all participants will be analysed according to their randomised group irrespective of treatment actually received. Analyses will include observed data only; no imputation of missing outcome data will be performed. Analyses will be performed using Stata v18 or later, by a statistician who is blinded to group allocation. Economic analyses The economic analyses will follow the same approach as the statistical analysis. We will use an intention-to-treat analysis, taking the NHS and social care perspective. As this is a feasibility trial, we will report descriptive data only for each trial arm, with confidence intervals for between group comparisons. No p -values will be reported. Primary analysis will be based on complete case data. However, losses to follow-up at data collection points will be presented for both primary and secondary outcomes. Missing outcome data will also be discussed, along with its causes. In order to cost the intervention, we will collect information on the resource use and costs of delivering the STABILISE intervention depending the type of delivery i.e., face-to-face, online or by phone. It will include costs on training and salaries, course materials, travel expenses, supervision and administration costs. The costs of the intervention will be estimated as a cost per participant. Sensitivity analyses will be conducted using the minimum and maximum number of sessions of the STABILISE intervention. Qualitative data analysis Qualitative interviews will be audio-recorded and then transcribed. Participants’ responses will be read closely and coded using a framework approach, informed by the framework for assessing intervention acceptability proposed by Sekhon and colleagues [50]. Data relevant to each category will be compared and summarised and non-conforming cases examined closely to understand similarities and differences in perspective. Interview recordings will be transcribed by a member of the study team, or a suitable individual working with the team who has signed a confidentiality agreement. Data Management and Storage Information gathered electronically will make use of data capture platforms that conform to U.K. NHS data governance standards. Information will be stored according to standard practice within the NHS services hosting the intervention. Hard copies of information / measures gathered as part of this research study will be anonymised and stored in a locked filing cabinet in a locked office in the Department of Psychology, University of Exeter or a locked cabinet in a locked office on local participating NHS Trust premises. Participants will be identified by a code, with the document linking participant name with ID code being stored separately to the rest of the data, and accessible only to measures of the research team. Consent forms will be stored in a locked cabinet separately to data. Audio recordings will be recorded directly to, or immediately transferred in digital form to, a secure data storage area hosted by the University of Exeter (Secure Data Research Hub: SDRH). Personal data will be transferred and stored only where necessary. Study data will be stored in linked-anonymous form. General Data Protection Regulation (2018) will be followed, and the NHS services providing therapy will abide by the Information Governance requirements of their service. Within NHS services providing the therapy, participant information will not be stored anonymously as it will form part of the patient record. At the end of the study any anonymised paper data will be scanned into electronic form or entered into electronic databases (if not already done) and stored securely in the secure data storage area of the University of Exeter and the original paper copies and audio-recordings destroyed confidentially. The project CI will act as custodian for the data. If the CI leaves employment of the University of Exeter, a data custodian will be appointed by the University of Exeter (a member of the research group or of Exeter IT Services) who will manage continued archiving of the data. Anonymised data will be retained for 20 years. Personally identifiable information will be stored for 12 months after the end of the study to enable sufficient time for the study data to be analysed and a summary of the results to be sent to participants who requested these at study entry. Clinical data gathered as part of the individual’s treatment within the clinical services hosting the therapy will be stored according to local protocols on the retention of NHS clinical records. The study team members will have access to the final dataset, with the agreement of the CI. Consent will be sought from participants to share anonymised data with other researchers for secondary analyses. Because of the potentially sensitive nature of the data and the potential for participants to be identifiable by their data by some members of the public, the public will not be given unrestricted access to the data. In accordance with good practice and institutional policy the research database will be registered with the University of Exeter public access database. The dataset will be anonymous and will be registered with a metadata only record, allowing the research team to control access to the dataset, restricting it to appropriately qualified third parties. Data captured on paper will be entered by a member of the research team and checked by a second member of the team. Databases containing data returned by paper and through electronic data capture systems will be merged with assistance from Exeter Clinical Trials Unit prior to data analysis. Range checks will be used to help identify erroneous datapoints prior to analysis. Study Approvals The conduct of the trial will be in accordance with the Helsinki Declaration. The study has received approval from the U.K. Health Research Authority Research Ethics Service (IRAS ID: 335983), and from all relevant local approval bodies. Anticipated Risks and Benefits The administration of a novel therapeutic intervention raises the potential of risk to those in the trial, as well as potential benefit. We believe that the intervention is unlikely to pose significant risks: the approach is an adaptation of two widely used existing therapies (Behavioural Activation and Dialectical Behavioural Therapy), both of which have been delivered previously by our team to people with bipolar disorder in case series and trial contexts with no significant concerns about therapy safety resulting [18,25]. We are currently completing a case series evaluation of the STABILISE approach: at the time of writing all 12 participants have completed the acute phase of therapy with no significant concerns arising regarding the safety of the intervention. Reactions to therapy will be monitored by therapists and within clinical supervision and standard operating procedures relating to monitoring and reporting adverse events will be followed. In this study participants are allocated at random to receive either TAU, or TAU plus the novel intervention. Therefore, there is a risk that a participant may be disappointed by allocation to the former arm. The inclusion of a treatment as usual comparator arm is necessary in order to address some of the feasibility aims (to establish the acceptability of procedures to be used in a definitive trial, including randomisation). Participants will be informed of the nature and purpose of the randomisation element. They will be called by an unblinded member of the study team to inform them of their allocation; their response to this will be monitored including the offer of a follow-up call the following day. Participants in both arms will be directed towards sources of support in the local community and nationally. It will be made clear to those in the usual care arm that whilst participants currently receiving psychological therapy for bipolar disorder will not be eligible to join the study, no restrictions are placed on the treatments that participants can choose to access outside of the study whilst they are a part of it. Because the treatment is experimental it is not currently planned that it will be routinely offered to trial participants following study completion. There is a chance that completion of study measures may induce distress. Our experience of using similar methods in previous research projects is that a significant adverse reaction is rare and if it occurs it is transient. The information sheet will make clear to participants that filling in the measures may temporarily lower mood or cause distress. The therapist/researcher will ask participants if they suffer any adverse reaction completing measures and will follow service or research distress management protocols if a significant level of distress is observed. Participants will be contacted within a week of completing the initial assessment to check on their welfare and to develop a bespoke plan for supporting participants as they move through the study (e.g. texts to check in with them, occasional planned calls, etc). The sponsor holds indemnity policies to allow compensation of trial participants if formal claims of harm are made and upheld. Adverse Events We will monitor and record both serious and non-serious adverse events. Adverse event reports will be solicited at follow-up points and monitored during all research contacts and through inspection of HEQ responses. An adverse event (AE) is defined by the HRA as any untoward occurrence or worsening of an unintended sign, symptoms or disease that occurs during participation, regardless of any relation to participation. In the STABILISE study, an adverse event will be recorded only when medical / clinical assessment or treatment is sought for a new or worsening sign, symptom or disease, unless the event appears to be a result of participation in the study. An adverse event will be classified as serious if it results in: death, life threatening injury or condition, permanent impairment to a body structure, body function or the capacity of the individual to function in daily life; hospitalisation or extension of existing hospitalisation; foetal death, or a congenital abnormality or birth defect. Symptoms of Bipolar Disorder themselves are not defined as adverse events. However, deterioration in mental state that results in the person accessing emergency support will be classed as an adverse event. Any AEs that researchers or therapists believe may be study related, may merit a classification of “severe” (even if not technically meeting SAE criteria), or may constitute an SAE will be required to be reported to the site PI, Trial Manager and the CI within 24 hours. Other AEs must be reported to the PI, Trial Manager and CI within one week. The reporting period for all events and reactions will be from intake assessment to completion of the 52 week follow-up point. The only expected reactions to the therapy and / or trial procedures are distress or symptom exacerbation (including behaviours such as self-harm, suicidal behaviour or substance use which may be considered to be part of the symptom set that individual typically experiences or may be considered to be coping responses in the face of distress or symptom exacerbation). It is recognised that those participants in the intervention arm have more contact with the study team (and therefore more opportunity to report adverse events) than do those in the usual care arm, by virtue of attending therapy sessions. Thus, we may expect a higher rate of adverse events reported in the former arm. In this study particular attention will be paid to those events that appear to be caused by research or therapy participation. Criteria for Discontinuation Individual participants will discontinue their involvement if either: i) the participant does not wish to continue with the intervention and study; ii) the participant experiences an unexpected serious adverse reaction (mental or physical health event that results in significant impairment, hospitalisation or death) that is judged to be the direct result of the intervention or trial participation, where discontinuation is judged to be in the best interests of the participant by the participant or sponsor (with advice from the Trial Steering Committee); iii) the participant and / or therapy / research team believe that the intervention or trial participation will result in, or is likely to result in, a serious adverse reaction if continued; iv) the participant does not attend more than three consecutive therapy sessions without explanation; this will be judged to indicate discontinuation of therapy. Over the period that the participant does not attend sessions, efforts will be made by the therapist to contact the participant. Participant choice to discontinue therapy will not be assumed to mean automatic withdrawal from the trial. Should an unexpected serious adverse reaction occur to either the therapy or the trial procedures, and this is judged to be directly related to trial participation or to the therapy, the trial will be temporarily halted pending investigation and analysis of the extent to which future risk can be mitigated against. If it is judged that this is not possible, the trial will be discontinued. This process will be led by the sponsor in collaboration with the TSC chair and CI. Should information come to light from external sources that indicates that the therapy intervention or trial procedures are unsafe, the same process will be followed. Patient and Public Involvement Throughout this study we are working with a patient and public involvement panel (PPI panel) of individuals with personal experience of bipolar disorder, or who have a relative with bipolar disorder. The panel have contributed to the design of the therapy protocol and the materials for patients such as the information sheet, consent form and interview topic guide; a subgroup contributed to the initial design of the study itself. The panel will advise on the running of this study throughout. Trial Governance The Trial Steering Committee (TSC) includes independent members with academic and / or clinical expertise, and / or expertise based on personal experience. Also included are the CI and trial statistician. The TSC will meet approximately five times over the life of the project and will be responsible for advising the trial team on the conduct of the study. Given the relatively small scale of the trial a separate Data Monitoring Committee (DMC) has not been convened. Instead, the DMC functions (reviewing data collected including adverse events and making recommendations for the future conduct of the trial) are included within the terms of reference of the TSC. Approval will be sought from the sponsor and the relevant national regulatory bodies for all substantive changes to the protocol and these will be communicated externally via an update to the ISRCTN registration record. Role of the Funder and Sponsor Ultimate authority over the management of the study lies with the study sponsor. Neither the funder nor the sponsor of the study were involved in the design of the study and will not be involved in the collection, analysis or interpretation of data, or the writing of the study report. Dissemination The data arising from the study will be the property of the University of Exeter and the Chief Investigator. On completion of the study, the data will be analysed and tabulated and a Final Study Report prepared. The full study report will be made available in open access form via the University of Exeter and publication via a peer reviewed journal will be sought, acknowledging contributions to the study in line with journal policy. Findings will also be disseminated through academic conference presentations or posters, and publicly following a dissemination strategy to be developed with the PPI panel. Participants will be asked to state whether they wish to receive a copy of the findings which they will be sent once these have been finalised. In order to protect participant anonymity, the raw data will not be made publicly accessible. Authorship of the final trial report will be in line with the recommendations of the International Committee of Medical Journal Editors [51]. Trial Status The start date of the trial was 28 th March 2024. Recruitment is running from April 2024 to June 2025 inclusive. Follow up will last 52 weeks, with the entire study period lasting for 28 months. Discussion Expected findings This trial is designed to assess the feasibility, acceptability and safety of a randomised controlled trial of an adapted form of behavioural therapy for individuals with ongoing bipolar symptoms or cyclothymic disorder. To do so we will employ a mixed-methods approach whereby information about intervention acceptability is derived both from quantitative measures of attendance and completion and participant acceptability ratings, as well as from qualitative information gathered via interview and feedback questionnaire. Our study builds on an intervention co-development phase with individuals with lived experience of bipolar disorder, and also upon a case series in which 12 people received the resulting intervention. The case series met pre-determined continuation criteria, allowing progression to the current trial to address uncertainties prior to conducting a definitive, randomised, controlled trial of the intervention. Progression to the definitive trial will be determined according to performance against the set of continuation criteria described here. Limitations As this is a feasibility trial it is not designed to assess the clinical effectiveness of the intervention. Whilst this study will benefit from the information provided by the inclusion of a second trial site, the feasibility conclusions drawn may not apply to all possible additional sites in a future definitive trial. Consequently planning and decision-making with respect to any future trial will take into account additional information available, outside of the scope of the current study. Conclusion This study is an early step in establishing the clinical and cost effectiveness of an adapted form of behavioural therapy for people who find their bipolar mood issues persist outside of major affective episodes. In the longer term, if effectiveness is demonstrated, the intention is that it could be routinely delivered within the U.K. health service. Abbreviations AE Adverse Event ALS Affective Lability Scale ASRM Altman Scale for Rating Mania BA Behavioural Activation therapy BADS-SF Behavioral Avoidance in Depression Scale – Short Form BARS Brief Adherence Rating Scale BD Bipolar Disorders BDI Beck Depression Inventory BRQ Bipolar Recovery Questionnaire CI Confidence Interval CI Chief Investigator DBT Dialectical Behaviour Therapy DSM-V Diagnostic and Statistical Manual of Mental Disorders, fifth edition EQ-5D-5L EuroQoL 5 Dimension 5 Level GAD-7 Generalised Anxiety Disorder 7-item scale HAM-D Hamilton Depression Rating Scale HEQ Health Economics Questionnaire ICD-11 International Classification of Diseases 11 th Revision IEBS Inter-episode bipolar symptoms NHS U.K. National Health Service NIHR National Institute for Health Research PHQ-9 Patient Health Questionnaire 9 item scale PPI Patient and Public Involvement QALYS Quality Adjusted Life Years QoL-BD Quality of Life in Bipolar Disorder scale SAE Serious adverse event SCID-5 Structured clinical interview for DSM-V SD Standard Deviation STABILISE Experimental treatment evaluated in this study TAU Treatment as usual TSC Trial Steering Committee PU & NU Positive and Negative Urgency Scales Declarations Ethics Approval and Consent to Participate The study has received approval from the U.K. Health Research Authority Research Ethics Service (IRAS ID: 335983), and from all relevant local approval bodies. Potential participants will receive full information about the study before giving consent and will have opportunity at the screening call, and before and during the intake assessment, to ask questions and discuss the study. Researchers will be fully trained in taking informed consent, including assessment of capacity to consent where appropriate. Consent will be taken only from individuals with capacity to make an informed decision on their participation. Consent for Publication Not applicable. Availability of Data and Material Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Competing Interests Kim Wright occasionally receives payment in addition to her usual salary for delivery of workshops on psychological interventions for bipolar disorder to academic and healthcare organisations. Sandra Bucci is a director and shareholder of CareLoop Health Ltd, a University of Manchester start-up to develop and market digital solutions for mental health problems, currently in schizophrenia and postnatal depression. Funding The trial described by this protocol is funded by the National Institute for Health Research Advanced Fellowship Programme (ref: NIHR 302220) awarded to Kim Wright. SB discloses support for publication of this work from a National Institute for Health and Care Research research professorship (NIHR300794) and the NIHR Manchester Biomedical Research Centre (NIHR 203308). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Authors' contributions All authors contributed to the conception and design of the study protocol. KW drafted the manuscript and all other authors contributed to the editing of the final manuscript. Acknowledgements The study is supported by the UK Clinical Research Network with respect to participant recruitment, and by the University of Exeter Clinical Trials Unit with respect to trial management, database integration and randomisation. We would like to thank Prof Judit Simon and Dr Susanne Mayer for permission to use the HEQ. The study is sponsored by the University of Exeter, Stocker Road, Exeter EX4 4PY, U.K. References Pini S, De Queiroz V, Pagnin D, Pezawas L, Angst J, Cassano GB, Wittchen HU. Prevalence and burden of bipolar disorders in European countries. European Neuropsychopharmacology. 2005 Aug 1;15(4):425-34. Simon J, Pari AA, Wolstenholme J, Berger M, Goodwin GM, Geddes JR. The costs of bipolar disorder in the United Kingdom. Brain and Behavior. 2021 Oct;11(10):e2351. Paykel ES, Abbott R, Morriss R, Hayhurst H, Scott J. Sub-syndromal and syndromal symptoms in the longitudinal course of bipolar disorder. The British Journal of Psychiatry. 2006 Aug;189(2):118-23. MacQueen GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT. Subsyndromal symptoms assessed in longitudinal, prospective follow‐up of a cohort of patients with bipolar disorder. Bipolar Disorders. 2003 Oct;5(5):349-55. Gershon A, Eidelman P. Inter-episode affective intensity and instability: predictors of depression and functional impairment in bipolar disorder. Journal of Behavior Therapy and Experimental Psychiatry. 2015 Mar 1;46:14-8. Kochman FJ, Hantouche EG, Ferrari P, Lancrenon S, Bayart D, Akiskal HS. Cyclothymic temperament as a prospective predictor of bipolarity and suicidality in children and adolescents with major depressive disorder. Journal of affective disorders. 2005 Mar 1;85(1-2):181-9. Samalin L, de Chazeron I, Vieta E, Bellivier F, Llorca PM. Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder. Bipolar disorders. 2016 Mar;18(2):164-73. Roux P, Raust A, Cannavo AS, Aubin V, Aouizerate B, Azorin JM, Bellivier F, Belzeaux R, Bougerol T, Cussac I, Courtet P. Associations between residual depressive symptoms, cognition, and functioning in patients with euthymic bipolar disorder: results from the FACE-BD cohort. The British Journal of Psychiatry. 2017 Dec;211(6):381-7. Stanislaus S, Faurholt-Jepsen M, Vinberg M, Coello K, Kjaerstad HL, Melbye S, Sletved KS, Christensen EM, Frost M, Bardram JE, Kessing LV. Mood instability in patients with newly diagnosed bipolar disorder, unaffected relatives, and healthy control individuals measured daily using smartphones. Journal of Affective Disorders. 2020 Jun 15;271:336-44. Judd LL, Schettler PJ, Akiskal HS, Coryell W, Leon AC, Maser JD, Solomon DA. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Archives of general psychiatry. 2008 Apr 1;65(4):386-94. Alda M, McKinnon M, Blagdon R, Garnham J, MacLellan S, O'Donovan C, Hajek T, Nair C, Dursun S, MacQueen G. Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study. The British Journal of Psychiatry. 2017 Jan;210(1):54-60. Yilmaz S, Huguet A, Kisely S, Rao S, Wang J, Baur K, Price M, O'Mahen H, Wright K. Do psychological interventions reduce symptoms of depression for patients with bipolar I or II disorder? A meta-analysis. Journal of affective disorders. 2022 Mar 15;301:193-204. Mazzarini L. The treatment of cyclothymia. The Treatment of Bipolar Disorder: Integrative Clinical Strategies and Future Directions. 2017 Feb 9:123. Ciharova M, Furukawa TA, Efthimiou O, Karyotaki E, Miguel C, Noma H, Cipriani A, Riper H, Cuijpers P. Cognitive restructuring, behavioral activation and cognitive-behavioral therapy in the treatment of adult depression: A network meta-analysis. Journal of Consulting and Clinical Psychology. 2021 Jun;89(6):563. Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020 Feb;19(1):92-107. Richards DA, Ekers D, McMillan D, Taylor RS, Byford S, Warren FC, Barrett B, Farrand PA, Gilbody S, Kuyken W, O'Mahen H. Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial. The Lancet. 2016 Aug 27;388(10047):871-80. Weinstock LM, Melvin C, Munroe MK, Miller IW. Adjunctive behavioral activation for the treatment of bipolar depression: a proof of concept trial. Journal of Psychiatric Practice. 2016 Mar 1;22(2):149-58. Wright, K., Mostazir, M., Bailey, E., Dunn, B. D., O’Mahen, H., Sibsey, M., & Thomas, Z. (2022). Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series. Brain Sciences , 12 (10), 1407. Linehan M. Cognitive-behavioral treatment of borderline personality disorder. Guilford press; 1993 May 14. Swales MA, Dunkley C. Structuring the Wider Environment and the DBT Team. The Oxford Handbook of Dialectical Behaviour Therapy. 2018 Oct 25:217. DeCou CR, Comtois KA, Landes SJ. Dialectical behavior therapy is effective for the treatment of suicidal behavior: A meta-analysis. Behavior therapy. 2019 Jan 1;50(1):60-72. Haktanır A, Callender KA. Meta-analysis of dialectical behavior therapy (DBT) for treating substance use. Research on education and psychology. 2020;4(Special Issue):74-87. Ciesinski NK, Sorgi-Wilson KM, Cheung JC, Chen EY, McCloskey MS. The effect of dialectical behavior therapy on anger and aggressive behavior: A systematic review with meta-analysis. Behaviour research and therapy. 2022 Jul 1;154:104122. Jones BD, Umer M, Kittur ME, Finkelstein O, Xue S, Dimick MK, Ortiz A, Goldstein BI, Mulsant BH, Husain MI. A systematic review on the effectiveness of dialectical behavior therapy for improving mood symptoms in bipolar disorders. International Journal of Bipolar Disorders. 2023 Feb 5;11(1):6. Wright K, Dodd AL, Warren FC, Medina-Lara A, Dunn B, Harvey J, Javaid M, Jones SH, Owens C, Taylor RS, Duncan D. Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme). International Journal of Bipolar Disorders. 2021 Dec;9:1-3. Herdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Quality of life research. 2011 Dec;20:1727-36. Avery KN, Williamson PR, Gamble C, Francischetto EO, Metcalfe C, Davidson P, Williams H, Blazeby JM. Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies. BMJ open. 2017 Feb 1;7(2):e013537. Kahan BC, Hindley J, Edwards M, Cro S, Morris TP. The estimands framework: a primer on the ICH E9 (R1) addendum. bmj. 2024 Jan 23;384. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013. First MB, Williams JB, Karg RS, Spitzer RL. Structured Clinical Interview for DSM-5 Disorders–Research Version (SCID-5-RV). Arlington: American Psychiatric Assocation. 2014. Oliver MN, Simons JS. The affective lability scales: Development of a short-form measure. Personality and individual differences. 2004 Oct 1;37(6):1279-88. Kroenke K, Spitzer RL, Williams JB. The PHQ‐9: validity of a brief depression severity measure. Journal of general internal medicine. 2001 Sep;16(9):606-13. Hamilton M. A rating scale for depression. Journal of neurology, neurosurgery, and psychiatry. 1960 Feb;23(1):56. World Health Organization. ICD-11: International classification of diseases (11th revision). 2022. Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics: The Journal of Applied Statistics in the Pharmaceutical Industry. 2005 Oct;4(4):287-91. Whitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Statistical methods in medical research. 2016 Jun;25(3):1057-73. Fylan B, Tomlinson J, Raynor DK, Silcock J. Using experience-based co-design with patients, carers and healthcare professionals to develop theory-based interventions for safer medicines use. Research in Social and Administrative Pharmacy. 2021 Dec 1;17(12):2127-35. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Archives of general psychiatry. 1961;4:561-71. Altman EG, Hedeker D, Peterson JL, Davis JM. The Altman self-rating mania scale. Biological psychiatry. 1997 Nov 15;42(10):948-55. Michalak EE, Murray G, CREST. BD. Development of the QoL. BD: a disorder‐specific scale to assess quality of life in bipolar disorder. Bipolar disorders. 2010 Nov;12(7):727-40. Jones S, Mulligan LD, Higginson S, Dunn G, Morrison AP. The bipolar recovery questionnaire: psychometric properties of a quantitative measure of recovery experiences in bipolar disorder. Journal of affective disorders. 2013 May 31;147(1):34-43. Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Archives of internal medicine. 2006 May 22;166(10):1092-7. Bech P, Rafaelsen OJ, Kramp P, Bolwig TG. The mania rating scale: scale construction and inter-observer agreement. Neuropharmacology. 1978 Jun 1;17(6):430-1. Jacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology. 1991; 59:12-19. Simon, J, Mayer, S. HEQ (Health Economics Questionnaire), Version 08-09-2016. Vienna: Department of Health Economics, Center for Public Health, Medical University of Vienna. 2016. Cyders MA, Smith GT, Spillane NS, Fischer S, Annus AM, Peterson C. Integration of impulsivity and positive mood to predict risky behavior: development and validation of a measure of positive urgency. Psychological assessment. 2007 Mar;19(1):107. Manos RC, Kanter JW, Luo W. The behavioral activation for depression scale–short form: development and validation. Behavior therapy. 2011 Dec 1;42(4):726-39. Byerly MJ, Nakonezny PA, Rush AJ. The Brief Adherence Rating Scale (BARS) validated against electronic monitoring in assessing the antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. Schizophrenia research. 2008 Mar 1;100(1-3):60-9. Skivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, Boyd KA, Craig N, French DP, McIntosh E, Petticrew M. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. bmj. 2021 Sep 30;374. Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC health services research. 2017 Dec;17:1-3. International Committee of Medical Journal Editors. Defining the role of authors and contributors. Cited 2024 June 19. Available from: https://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors. Cite Share Download PDF Status: Published Journal Publication published 10 Jul, 2025 Read the published version in Pilot and Feasibility Studies → Version 1 posted Editorial decision: Minor revision 10 Apr, 2025 Reviewers agreed at journal 02 Apr, 2025 Reviewers invited by journal 17 Jan, 2025 Editor assigned by journal 06 Nov, 2024 First submitted to journal 08 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5223139","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":403688837,"identity":"7de374ca-7a7f-4b43-9ed8-28de4669f99b","order_by":0,"name":"Kim Wright","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3RMWrDMBTG8S8IlOWZrK+Tr/CEIWQo9lVUDM7SAwQKiSGQyQfI0FsUWgodBAbnHCWQrC5dOmSoTQLZbI+B6D8K/dAHAny+G0zcKFcEhkC5y5nuJiZX7ky0tsNIBG0b0jynSYaRKUhU8DWLP8LiZ0+IQ3BmO8ljS54PnH5ugjezRWpyztwA4jiVKnjnGsqC53nPsEl9IXT8s1j1k6h95eQ4bohGjbIhPcPMmqR8dWylyqKHrezMhg62k8iuMHtyy0TK8vuXFi/hZJxJJ4EC2h1P5/3S+yvXkqEXfT6f7w77B4MFPPZFdKOdAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-3865-9743","institution":"University of Exeter","correspondingAuthor":true,"prefix":"","firstName":"Kim","middleName":"","lastName":"Wright","suffix":""},{"id":403688838,"identity":"a61fb9e7-5b61-46b0-a34c-e2c2aecb0869","order_by":1,"name":"Fiona C Warren","email":"","orcid":"","institution":"University of Exeter","correspondingAuthor":false,"prefix":"","firstName":"Fiona","middleName":"C","lastName":"Warren","suffix":""},{"id":403688839,"identity":"c68b480c-cabb-4fd4-9c61-585ff378b672","order_by":2,"name":"Sandra Bucci","email":"","orcid":"","institution":"University of Manchester division of psychology and mental health","correspondingAuthor":false,"prefix":"","firstName":"Sandra","middleName":"","lastName":"Bucci","suffix":""},{"id":403688840,"identity":"63c4bae9-55ee-438d-9fa7-a4d156d8487d","order_by":3,"name":"Barnaby Dunn","email":"","orcid":"","institution":"University of Exeter","correspondingAuthor":false,"prefix":"","firstName":"Barnaby","middleName":"","lastName":"Dunn","suffix":""},{"id":403688841,"identity":"e084052f-0d75-4269-a9ee-a89263a897e0","order_by":4,"name":"Steven Jones","email":"","orcid":"","institution":"Lancaster University","correspondingAuthor":false,"prefix":"","firstName":"Steven","middleName":"","lastName":"Jones","suffix":""},{"id":403688842,"identity":"3f7fa679-93ec-408c-a72a-340ee29f5a64","order_by":5,"name":"Heather O'Mahen","email":"","orcid":"","institution":"University of Exeter","correspondingAuthor":false,"prefix":"","firstName":"Heather","middleName":"","lastName":"O'Mahen","suffix":""},{"id":403688843,"identity":"b5e50d2b-785a-4bdb-896e-781ee7215b09","order_by":6,"name":"Rod Taylor","email":"","orcid":"","institution":"University of Glasgow","correspondingAuthor":false,"prefix":"","firstName":"Rod","middleName":"","lastName":"Taylor","suffix":""},{"id":403688844,"identity":"df3298e6-fef8-454d-8896-8841c59925b5","order_by":7,"name":"Antonieta Medina-Lara","email":"","orcid":"","institution":"University of Exeter","correspondingAuthor":false,"prefix":"","firstName":"Antonieta","middleName":"","lastName":"Medina-Lara","suffix":""}],"badges":[],"createdAt":"2024-10-08 08:03:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5223139/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5223139/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40814-025-01678-6","type":"published","date":"2025-07-10T15:58:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74534756,"identity":"1e694563-b72b-4d89-a116-994e9242c548","added_by":"auto","created_at":"2025-01-23 08:21:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":23811,"visible":true,"origin":"","legend":"\u003cp\u003eSchedule of enrolment, interventions, and assessments (following SPIRIT template).\u003c/p\u003e\n\u003cp\u003eTAU: treatment as usual; SCID-5: Structured Clinical Interview for DSM-V; HAM-D; Hamilton Depression Rating Scale; PHQ-9: Patient Health Questionnaire – 9 item; ALS: Affective Lability Scales; BMRS: Bech-Rafaelson Mania Scale for Rating Mania; Qol.BD: Quality of Life in Bipolar Disorder Scale; BRQ: Bipolar Recovery Questionnaire; GAD-7: Generalised Anxiety Disorder Questionnaire – 7 item; PU \u0026amp; NU: positive and negative urgency; BADS-SF: Behavioural Activation in Depression Scale – short form; HEQ: Health Economics Questionnaire; EQ-5D-5L: EuroQol 5 Dimension 5 Level Questionnaire; BARS: Brief Adherence Rating Scale; *administered only if participant is assessed in SCID-5 as in current major depressive episode; **completed by 15 participants in intervention arm.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5223139/v1/b626b418abe479c5477ef319.png"},{"id":86700096,"identity":"55a644b8-9c9e-48ce-8513-27002e5a6a6a","added_by":"auto","created_at":"2025-07-14 16:11:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":871236,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5223139/v1/604937e0-5682-49cd-b07f-88b09fc39478.pdf"}],"financialInterests":"","formattedTitle":"The clinical and cost effectiveness of behavioural therapy for interepisode bipolar symptoms (STABILISE): A randomised, controlled feasibility trial.","fulltext":[{"header":"Background","content":"\u003cp\u003eBipolar spectrum disorders (Bipolar I or II Disorder, Cyclothymic Disorder) result in substantial personal and societal costs and affect around 1 in 20 people across their lifetime [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn addition to major episodes of depression or mania, people with bipolar spectrum disorders can experience ongoing bipolar symptoms (inter-episode Bipolar symptoms (IEBS)). With IEBS, depressive symptoms tend to be more frequent relative to hypomanic symptoms [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] and instability of mood is common [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eInterventions are needed for IEBS for three reasons. First, they are common: ongoing bipolar symptoms in the form of subclinical low mood or mood instability are experienced by up to half of those with Bipolar I or II Disorder who are not in a major episode [\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e], and on average people with bipolar I or II disorder spend around twice as long experiencing residual symptoms as they spend in acute episodes [\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. Second, they are associated with significant distress and impairment, including increased psychiatric comorbidity and poorer functioning [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. Third, the ongoing mood instability that constitutes cyclothymic disorder is associated with risk of developing full depression and mania [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e], which can be costly to the health service and the wider society, and costly to patients and families. Indeed, in a UK study, for each unit increase in average levels of depressive or manic symptoms there was an increase in societal costs of 7% and 11%, respectively [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eDespite the impact of IEBS studies evaluating approaches to helping people with this disabling presentation are scarce. Furthermore whilst some have examined the effects of pharmacological agents on residual symptoms [\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e], relatively few consider their impact on mood instability.\u003c/p\u003e\n\u003cp\u003ePsychological therapies for individuals with bipolar disorder are valued by service users, and are recommended within various national treatment guidelines, yet the extant literature does not provide direct guidance on the optimal psychological treatment for people with IEBS, with studies tending to focus on relapse prevention or alleviation of acute depression as the primary target of therapy [\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e] or specifically upon cyclothymic disorder [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Thus, we do not currently have a psychological treatment that seeks to address the common ongoing mood symptoms (subclinical low mood and mood instability) that people with bipolar disorder (BD) or cyclothymic disorder (CD) present with, nor a therapy that has been tested across the bipolar spectrum with respect to these issues.\u003c/p\u003e\n\u003cp\u003eOur approach (STABILISE: Study of Therapy for Bipolar Interepisode Symptoms) brings together two behavioural therapies that are commonly used and effective with related populations to address key therapy targets also relevant to IEBS: reduction of depressive symptoms through supporting meaningful behaviours, and management of problematic affective instability. The resulting therapy is designed to support people with BP or CD in managing ongoing difficulties with low mood or mood instability, including the impact of these on everyday life.\u003c/p\u003e\n\u003cp\u003eBehavioural Activation (BA) is used extensively in the treatment of acute unipolar depression [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. It is informed by the behavioural theory of depression whereby depression is hypothesised to be maintained by a reduction in access to positive reinforcement from the person\u0026rsquo;s context, and a subsequent increase in \u0026ldquo;avoidance\u0026rdquo; behaviours that function to reduce negative affect rather than to approach valued goals. Correspondingly BA involves supporting the person to access previous and new sources of reward through scheduling goal and value-consistent activities into the week and learning or re-accessing skills for managing barriers to engaging fully in these activities. BA is often considered to represent a parsimonious and relatively straightforward approach to disseminate, potentially reducing training costs and broadening the range of health professionals who may be able to deliver it [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. Two reports of case series data on its use in people with acute bipolar depression [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e] describe high acceptability rates, no safety concerns and encouraging patterns of change on clinical outcome measures.\u003c/p\u003e\n\u003cp\u003eDialectical behaviour therapy (DBT) is a form of behavioural therapy originally developed for women with borderline or emotionally unstable personality disorder [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e] and later applied across genders and across multiple problem areas. It is based upon the biosocial theory which posits that emotion dysregulation is the outcome of an interaction between an emotionally sensitive temperament and an early environment that invalidates their emotional responses. DBT teaches the person skills for recognising and responding to emotional states, and for managing the situations that can trigger these responses. A behavioural framework is used to understand the interaction between the person and their context, and the therapist stance models appropriate validation of emotion and a dialectical outlook, whereby it is acknowledged that two seemingly contradictory accounts can both be true (e.g. \u0026ldquo;I am an okay person and I can adapt my behaviours in this context to get a better outcome for myself and others\u0026rdquo;. The full DBT programme includes group skills training, individual therapy sessions, skills coaching outside of sessions, structuring the environment and group consultation between therapists; however, partial versions of DBT, often called DBT-informed interventions, have been developed. DBT, including DBT-informed interventions, has been tested for a range of patient groups, including people without a diagnosis of personality disorder, where emotional dysregulation plays a role in the presenting issues [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. It has found to be effective in reducing substance use and self-harm (both being behaviours that are often used by individuals to cope with intense, seemingly unmanageable affect) and problematic anger. A small number of case series and feasibility studies have explored DBT-informed interventions for people with bipolar disorder, with promising outcomes in terms of acceptability and likely clinical benefit; these vary in the extent to which they adhere to the traditional DBT programme versus include concepts and techniques influenced by DBT or other emotion regulation programmes [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. In addition, except for one study [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e], these studies do not focus specifically on inter-episode symptoms or include individuals with cyclothymic disorder.\u003c/p\u003e\n\u003cp\u003eWith input from people with lived experience of bipolar disorder, and family members, we integrated concepts and techniques from DBT within a BA protocol used previously with individuals with bipolar depression [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. An initial examination of the safety and acceptability of the resulting therapy was conducted within in a case series of 12 individuals with BD or CD and ongoing low mood or mood instability. At the time of writing, the acute treatment phase of the case series is complete and pre-determined rules to allow progression to the next phase of evaluation, a randomised controlled feasibility trial, have been met (no serious concerns about therapy safety; instances of reliable improvement exceed instances of reliable deterioration). The protocol for this feasibility trial is presented here.\u003c/p\u003e\n\u003cp\u003eThe overall aim of this study is to determine the likely feasibility, acceptability and safety of the research procedures, including the therapy protocol, to design a future definitive randomised trial to determine the clinical and cost effectiveness of the STABILISE therapy programme.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ei) To inform the recruitment and timeline of a future fully-powered trial, by informing estimates of the number of participants who will need to be identified, approached, consented, randomised and who are likely to complete outcome assessments;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eii) To refine future trial procedures by establishing the acceptability and experience of the trial process to participants. This includes acceptability and experience of randomisation and outcome measures;\u003c/p\u003e\n \u003cp\u003eiii) To inform selection of the optimal primary outcome measure in a future trial by assessing the performance of selected candidate primary outcome measures with respect to level of acceptability to participants and participant-perceived relevance and value. Although not powered to detect a significant between group mean difference, we will scrutinise between group mean differences for each outcome measure, as well as relative rates of reliable improvement and deterioration, to assess sensitivity of the measure to the impact of the intervention.\u003c/p\u003e\n \u003cp\u003eiv) To inform estimation of sample size for a future trial by measuring data completeness at follow up (participant attrition) and standard deviation of the likely primary outcome measure (to compare to reports in published literature).\u003c/p\u003e\n \u003cp\u003ev) To characterise the comparator condition, treatment as usual, across individuals and sites.\u003c/p\u003e\n \u003cp\u003evi) To further explore the safety and acceptability of the treatment and, based on input from trial participants and clinicians, to further refine and develop the treatment manual and the procedures for training, supervising and assessing the competence of trial therapists.\u003c/p\u003e\n \u003cp\u003evii) To demonstrate feasibility outside of the lead site by including a second site.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003evii) To demonstrate feasibility outside of the lead site by including a second site.\u003c/p\u003e\n \u003cp\u003eviii) To estimate the cost of the intervention.\u003c/p\u003e\n \u003cp\u003eix) To assess the feasibility of collecting health care resource utilisation data and health-related quality of life data using the EQ-5D-5L [26].\u003c/p\u003e\n \u003cp\u003ex) To explore the feasibility of collecting momentary assessment (experience sampling) data at three time points (5 times per day, for 10 days, at each timepoint): the ultimate purpose of collecting these data in a future larger trial is to estimate mood instability and to examine process of change.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe criteria for progression to definitive trial are given in Table 1, presented in accordance with the framework proposed by Avery and colleagues [27].\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCriteria for progression to a definitive trial\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eRed\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAmber\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eGreen\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall safety of intervention and trial procedures as determined by TSC and sponsor\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCannot be made sufficiently safe for use in a definitive trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eCan be made sufficiently safe following modification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSufficiently safe for use in a definitive trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean recruitment rate per site over 15 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;2 participants per month at both sites\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;2 participants per month at one site and target sample size not reached, with clear plan for improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2 participants at both sites OR\u0026thinsp;\u0026lt;\u0026thinsp;2 participants at one site but overall target sample size reached \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOutcome measure completion at 30-week follow-up point (completion of candidate primary outcome measure at primary end point)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;55% of participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBetween \u0026ge;\u0026thinsp;55 and \u0026lt;\u0026thinsp;75% of participants, with clear plan for improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;75% of participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLevel of completion of intervention (defined as attending at least 6 therapy sessions) \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;50% of participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e50\u0026ndash;89% of participants, with clear plan for improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;90% of participants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u003cem\u003eNote\u003c/em\u003e. Red: Do not progress to the main trial (unless TSC agree exceptional circumstances and a mitigation plan is present); Amber: Progress if action plan to mitigate problems can be determined and agreed with the Trial Steering Committee (TSC); Green: Progress directly to the main trial. \u003csup\u003ea\u003c/sup\u003e Subsequent to reviewing information on adverse and serious adverse events arising during the trial. \u003csup\u003eb\u003c/sup\u003e To allow for a situation in which recruitment systems require a lead-in period at a site before becoming optimized, and this optimization period can then be accounted for in planning for a definitive trial. \u003csup\u003ec\u003c/sup\u003e Information will be collected on reasons for discontinuation to inform plan for enhancing retention in intervention and / or refinement of the estimand for a definitive trial [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e[Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e about here]\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis feasibility study protocol is reported according to the SPIRIT 2013 statement (see additional file 1 for a completed SPIRIT checklist).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis feasibility study has a two-arm randomised parallel controlled trial design. Participants will be randomised on a 1:1 ratio to Treatment as Usual (TAU) only (control arm) or TAU plus STABILISE programme (intervention arm). Outcome measures will be completed at baseline and at three follow-up points: 14, 30 and 52 weeks post study entry. We have selected 30 weeks as the primary end point to allow this to be immediately following the intervention period. The study takes a mixed-method approach whereby evaluation of therapy acceptability and potential impact is explored both qualitatively and quantitatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting and Participants\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe trial will be conducted across two sites in the U.K. (an NHS mental health Trust, and a specialist NHS outpatient psychological therapies service based at the University of Exeter) with participants allowed to be recruited from primary care services, secondary care mental health services and via self-referral. For details of study sites please see: https://www.isrctn.com/ISRCTN18207465. \u0026nbsp;Eligible participants will be aged 18 or over with a diagnosis of Bipolar Disorder (I,II, Other Specified Bipolar Disorder) or Cyclothymic Disorder, according to DSM-V[29] criteria assessed using the Structured Clinical Interview for DSM-V (SCID-5 [30]). Participants must report either current bipolar mood instability, defined as a score of at least 1.3 on the depression-elation subscale of the short form Affective Lability Scale (ALS [31]), or presence of at least mild depressive symptoms, defined as a score of at least 5 on the 9-item version of the Patient Health Questionnaire (PHQ-9 [32]). They must also be willing to engage in psychological therapy that focusses primarily on psychological work addressing ongoing bipolar symptoms or their impact on functioning, and must be able to attend regular therapy sessions. Participants must have sufficient competency in English such that study measures can be completed without the need for translation (to preserve the measure properties), have completed the intake measures, and be registered with a General Practice in the study site catchment area. Participants will not be included if they are currently experiencing a manic episode (assessed using the SCID-5) or severe major depressive episode (assessed using the SCID-5; the Hamilton Depression Rating Scale [33], an established, validated measure of current depression symptoms, will be used with participants who meet criteria for a current depressive episode to establish severity). We will not include participants with current substance dependence according to The International Classification of Diseases, 11\u003csup\u003eth\u003c/sup\u003e revision (ICD-11 [34]) criteria; ICD-11 rather than DSM-V criteria are used to permit assessment of substance dependence rather than the broader construct of substance use disorder. Participants receiving other psychological therapy for bipolar disorder or who present a risk of harm to themselves or others that cannot be safely managed in a community outpatient setting will not be included.\u003c/p\u003e\n\u003cp\u003eMedication status will not serve as an exclusion criterion but will be recorded. In both conditions participants will continue to be able to access routine care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 60 individuals will be recruited (target n=30 in Devon, and n=30 in Avon \u0026amp; Wiltshire). A sample size of 60 participants allows estimation of loss to follow-up within +/- 12 percentage points, assuming 20% attrition, and is sufficient to estimate the standard deviation in the candidate primary outcome measures [35,36].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomisation, Concealment of Allocation, and Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants eligible for the study will be randomised on a 1:1 ratio (with minimisation by trial site and medication status [currently prescribed medication for depression or Bipolar Disorder versus not prescribed such medication]) to Treatment as Usual (TAU) [control arm] or Treatment as Usual plus STABILISE programme (TAU + STABILISE) [intervention arm]. Allocation concealment during the randomisation process will be achieved through use of a validated password protected online randomisation tool programmed and hosted by the Exeter Clinical Trials Unit. The first six participants will be allocated using simple randomisation and then the minimisation procedure will commence, maintaining a stochastic element to the algorithm to allow concealment to be maintained. \u0026nbsp;The minimisation algorithm will take account of the allocations of the first six participants. Participants will be enrolled into the randomisation system and informed of their allocation by an unblinded researcher.\u003c/p\u003e\n\u003cp\u003eGiven the nature of the intervention, blinding of participants to allocation is not possible. Follow-up assessments will be conducted by separate researchers who are unaware of the participant\u0026rsquo;s allocation. At follow-up, outcome assessors researchers will be instructed to maintain blinding by reminding participants not to reveal their allocation during the contact. Outcome assessors will be asked to indicate at follow-up which treatment they believe the participants received, allowing us to test blinding status and analyse any correlation with outcome. The outcome assessors\u0026rsquo; blind will be maintained as far as possible; they will be deliberately unblinded only in exceptional circumstances where knowledge of the treatment arm is deemed essential to their management of the participant (e.g. certain Serious Adverse Events). Instances of deliberate or accidental un-blinding will be recorded; future data collection from that participant will be carried out by a member of the team who remains blinded. An unblinded researcher will collect data from participants that pertains to their allocation (qualitative and quantitative feedback about their experience of the study and of the therapy). All other members of the study team will be unblinded other than those performing statistical analyses on the data (health economist and statistician). Statistical and economic analyses will be performed by a statistician and health economists who are blinded to participant allocations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be identified from local NHS services including but not limited to primary care psychological therapies services, General Practices, secondary care mental health teams, early intervention services and secondary care psychological therapies services. In addition, advertisements for the study will be placed in healthcare settings, public places and distributed through traditional and social media, and third sector organisations. Potential participants who are interested in the study will be given the choice of contacting the researchers directly by telephone, email or post, or completing a \u0026ldquo;permission to contact\u0026rdquo; form which can be passed to the research team by their clinician or sent directly to the study team by the participant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter a potential participant contacts or is referred to the study, a member of the research team will answer any initial questions and have an initial discussion about the study if the person wishes. Following receipt from the participant of a completed form gaining their consent for contact and an initial telephone screening call (\u0026ldquo;permission to contact\u0026rdquo; form), the researcher will arrange a time to complete this with the participant. In the screening call the researcher will go through the inclusion and exclusion criteria with the participant, to give an indication of the likelihood that the participant will be eligible. Those likely to be eligible and willing to continue will be invited to the intake appointment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt the appointment the researchers will take written consent if the participant wishes to proceed and conduct the eligibility assessment. If the potential participant is eligible to partake in the study, is fully informed and has consented to participate, then they will be enrolled into the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants will be offered an honorarium of \u0026pound;20 for their participation at four points in the study: the intake assessment and the 14,30 and 52 week follow-up points.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing an approach informed by experience-based co-design [37], the STABILISE therapy programme was developed and refined through a series of workshops and other communications with patients and supporters, as well as input from therapists familiar with the component therapies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSTABILISE seeks to incorporate emotion regulation strategies into a behavioural approach that seeks to promote re-engagement with valued activities and meaningful routine. Specifically, STABILISE recognises that instability in behaviours and affect in IEBS are related, and aims to help participants find a balanced, sustainable pattern of activity that enables them to live well within their situation, to support them to change their situation where possible and needed, and to make changes to patterns of behaviour that lead to problems or distress. This typically entails reducing mood-driven behaviour and increasing behaviours guided by the person\u0026rsquo;s values, plans or goals. These principles apply equally to depressed versus hypomanic states.\u003c/p\u003e\n\u003cp\u003eRecognising that people with bipolar disorder have often experienced many years of threatening, uncontrollable shifts in affect, energy and motivation, STABILISE draws upon several key principles of DBT including an emphasis on validation of emotional experiences and a dialectical stance, balancing acceptance and change. It also incorporates, within the behavioural framework, techniques and ideas from DBT and other therapies that target emotion regulation.\u003c/p\u003e\n\u003cp\u003eThe intervention consists of up to 20 individual therapy sessions (plus up to 2 initial assessment sessions) of behavioural therapy, delivered up to 7 months (30 weeks). Therapy ends after 20 sessions or 7 months, whichever is sooner, and participants can choose to space sessions out over more than a week if they wish or to take a short break from therapy. Sessions are an hour long as default but with the option for participants to agree shorter or longer (up to 75 minute) session duration if needed. This is followed by a period of consolidation whereby participants can opt to see the therapist up to 3 times up until 12 months after starting therapy.\u003c/p\u003e\n\u003cp\u003eAll sessions will be audio-recorded (where participants consent to this) to allow for supervision and the refinement of a therapy adherence and competence measure.\u003c/p\u003e\n\u003cp\u003eTherapy will be delivered by at least three therapists with an existing training in cognitive behavioural, behavioural or dialectical behavioural therapy and experience of working with people with mood disorders. Therapists new to delivering the intervention will receive a 3-day training programme and all therapists will receive supervision every 1-2 weeks from the therapy developer or a STABILISE senior therapist whilst delivering therapy.\u003c/p\u003e\n\u003cp\u003eTherapy will be delivered face-to-face, online or by phone according to participant preference and what is feasible; local NHS service protocols will be followed in terms of telephone and online platform use. Face-to-face therapy will by default be delivered in the treatment centre; however, in keeping with the ethos of the approach (patient-centred, flexible, contextual and experiential) therapy sessions may take place outside of the centre if the participant wishes and it is appropriate and safe to do so. This may include practising activities together (e.g. visiting a shop) or sessions within the person\u0026rsquo;s home.\u0026nbsp;Participants will complete the Beck Depression Inventory (BDI) [38] and Altman Scale for Rating Mania (ASRM) [39] prior to each session and the scores used to inform their care, as well as forming part of the research data collected.\u003c/p\u003e\n\u003cp\u003eIt is anticipated that changes to the therapy protocol during the feasibility trial will be minor (i.e. will concern including or excluding specific techniques, or the wording and presentation of therapy materials, rather than the underpinning principles, therapeutic approach and overall structure). Changes to the therapy protocol will be timestamped allowing identification of which participants received which version.\u003c/p\u003e\n\u003cp\u003eThe comparison arm in this trial is TAU. This was chosen because of the absence of a \u0026ldquo;gold standard\u0026rdquo; therapy for inter-episode symptoms against which the novel therapy can be benchmarked. To characterise the content of TAU across trial sites, we will collect data on health services used by participants. There will be no restriction on the content of TAU, other than as part of the exclusion criteria for study entry whereby participants must not currently be receiving psychological therapy for bipolar disorder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this is a feasibility trial, the primary outcomes relate to the key feasibility objectives.\u003c/p\u003e\n\u003cp\u003eObjective 1 is to inform the recruitment and timeline of a future fully-powered trial. This will be evaluated using rates of recruitment from both sites (number of participants randomised per month), presented for each site and for both sites combined.\u003c/p\u003e\n\u003cp\u003eObjective 2 is to refine future trial procedures by establishing the acceptability and experience of the trial process to participants, including randomisation and completion of outcome measures. This will be evaluated by examining outcome measure completion rates including health economics measures, attrition across the two arms, and quantitative and qualitative acceptability data from participants. Descriptive statistics will be presented including within a CONSORT diagram showing participant flow through the study, including number expressing an interest, completing a screening call, attending intake assessment, giving informed consent, being randomised, and completion of each follow-up point. More detailed descriptive statistics showing completion of each measure at each follow-up point will be presented in tabular form.\u003c/p\u003e\n\u003cp\u003eObjective 3 is to determine the optimal primary outcome measure in a future trial. This will be achieved by examining per-measure completion rates, participant feedback on measures, participant rankings of importance, likely sensitivity to change, and presence of an established minimally important clinical difference value. At this stage, candidate future primary outcome measures include the PHQ9 [32], ALS-SF [31], brief Quality of Life in Bipolar Disorder Scale (QoL.BD [40]) and Bipolar Recovery Questionnaire (BRQ [41]). Completion rates for each measure will be presented at each time point; participant feedback on measures will be analysed qualitatively. Participant rankings of these four clinical outcome domains plus two additional potential secondary outcomes domains (anxiety and mania symptoms, measured by the Generalised Anxiety Disorder Questionnaire (GAD-7 [42]) and Bech Rating of Mania Scale (BRMS [43]) respectively), will be used to provide information on their value to participants: for each domain mean (SD) rank will be presented, where lower score equals higher rank, as well as number (%) of participants selecting each domain as first or second highest-ranked. Rankings will be gathered as part of an embedded study piloting three methods for establishing patient prioritisation of outcomes. In each method participants are asked to indicate the relative importance of change on each of the six outcome areas. For further details of the methods used please contact the corresponding author. To examine sensitivity of the measures to the impact of the intervention, between group mean differences will be calculated (with 95% confidence intervals), as will rates of reliable change [44] on the measures (reliable improvement, reliable deterioration). The information above will be considered within a stakeholder consensus meeting to agree the optimal primary (or co-primary) outcome measure(s) for a future definitive trial, with the ultimate decision made by the CI.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eObjective 4 is to inform estimation of sample size for a future trial. This will be evaluated by examining data completeness at follow up (participant attrition) as described for objectives 2 and 3, and standard deviation of candidate primary outcome measures (to compare with reports in published literature).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eObjective 5 is to characterise treatment as usual across individuals and sites. Data on treatment as usual will be presented descriptively based on health economic data collected at intake and at each follow up point.\u003c/p\u003e\n\u003cp\u003eObjective 6 is to further assess the safety and acceptability of the treatment and, based on input from trial participants and clinicians, to further refine and develop the treatment manual and the procedures for training, supervising and assessing the competence of trial therapists. With respect to safety the number of adverse events (AEs) and serious adverse events (SAEs) will be reported descriptively for each treatment group using an As Treated approach, whereby participants will be reported according to treatment actually received, irrespective of group allocation. We will also report the number and percentage of participants experiencing at least one SAE, as well as between group comparisons of number of individuals experiencing an SAE using risk difference and odds ratio with 95% confidence intervals. Acknowledging that AEs and SAEs are more likely to be reported by those in the STABILISE + TAU arm because of regular contacts with their therapist, we will particularly attend to the outcome of between group comparisons of study-related versus unrelated events. Safety will also be assessed by examining rates of reliable deterioration at 30 weeks (number of participants showing reliable deterioration in both arms).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWith respect to acceptability this will be evaluated by examining therapy uptake and completion rates: number of participants entering and completing therapy, mean (SD) number of sessions attended and minimum and maximum. It will also be assessed by evaluating quantitative and qualitative feedback from participants and therapists: mean (SD) and minimum and maximum of quantitative ratings on acceptability items; and thematic analysis of participant feedback. The inter-rater reliability of the therapy competence measure will be assessed by two raters independently assessing the same 51 recordings of therapy sessions and their scores being used to calculate the intraclass correlation coefficient using a two-way random effects model, for both consistency and absolute agreement (n=51 allows estimation of ICC of 0.8 with 95% CI of 0.7-0.9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eObjective 7 is to demonstrate feasibility outside of the lead site by including a second site. This will be evaluated by comparing rates of recruitment and retention across the two sites.\u003c/p\u003e\n\u003cp\u003eObjective 8 is to identify, measure and value the cost components for delivering the intervention. These costs will include any necessary training and materials, as well as staff costs and supervision if necessary. It will take into consideration whether the intervention was delivered face-to-face, online or by phone.\u003c/p\u003e\n\u003cp\u003eObjective 9 is to assess the feasibility of collecting health care resource utilisation data and health-related quality of life data using the EQ-5D-5L for obtaining utilities and estimating Quality-Adjusted Life Years (QALYs) at all timepoints. It will investigate the pattern of missingness as well as identifying which are the key cost drivers on resource utilisation.\u003c/p\u003e\n\u003cp\u003eObjective 10 is to examine the feasibility of collecting momentary assessment data and baseline, 14 and 30 weeks: this will be addressed by examining rates and pattern of missingness as well as through participant report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic information\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt the baseline eligibility assessment demographic information\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003eage, gender, ethnicity, perceived financial status, sexual orientation) will be collected.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient reported clinical outcome measures\u003c/p\u003e\n\u003cp\u003eIn addition to the PHQ-9 and ALS the following clinical outcome measures will be completed at baseline, 14, 30 and 52 week follow-up: BRMS, an 11-item observer-rated scale measuring level of current mania symptoms; QoLBD, a 12-item self-report measure of disorder-specific quality of life; GAD-7, a 7-item self-report measure of anxiety symptoms; BRQ, a 36-item self-report measure of sense of personal recovery; Life chart self-report, a self-report of number and duration of depressive and manic episodes in the period since last assessment (completed at 14, 30 and 52 week follow-up points only), completed with the support of the researcher; Health Economics Questionnaire (HEQ [45]) \u0026ndash; self-report of health economic variables (employment, healthcare resource use) over past 6 months (at intake) or since last contact (at follow up assessments); EQ-5D-5L \u0026ndash; a 5-item self-report measure of health-related quality of life, for obtaining utility values for estimating QALYs.. At this stage, candidate future primary outcome measures include the PHQ9, ALS, QoL.BD and BRQ.\u003c/p\u003e\n\u003cp\u003eQuantitative process measures\u003c/p\u003e\n\u003cp\u003eThe theoretical model underpinning the therapy hypothesises that mood related difficulties are maintained, at least in part, by individuals responding impulsively to intense mood states, and some of these responses further affecting mood as well as contributing to difficulties in everyday life. In order to test this hypothesis in a future, larger trial we plan to use the following self-report measures, which are included in the current study, to assess the acceptability of doing so:Positive and Negative Urgency Scales (PU \u0026amp; NU [46]), two 4-item scales measuring impulsive responding to positive and negative mood; Behavioural Activation in Depression Scale \u0026ndash; Short Form (BADS-SF[47]), a 9-item scale measuring behavioural avoidance versus approach within low mood (avoidance being a form of impulsive response to negative affect).\u003c/p\u003e\n\u003cp\u003eAs another means of assessing the process of change within therapy as part of a large, future trial we plan to measure mood and activity repeatedly to allow us to look at the inter-relationships between these. In the current study we plan to gather information on the feasibility and acceptability of collecting these data, having initially tested this method within our case series. Participants will be invited to report on their current mood and activity 5 times per day for 10 days via a purpose-built web application (momentary assessment block). These momentary assessment blocks will take place on three occasions: for 10 days following the intake assessment, for 10 days at 14 weeks post randomisation, and for 10 days following the 30-week follow-up point.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAdditional measures\u003c/p\u003e\n\u003cp\u003eAt the 30-week follow-up point, participants will complete a feedback questionnaire within which they will be asked to rate (on a scale from 1-4) their satisfaction with the therapy, how acceptable it was and the likelihood they would recommend it to a friend (for those in the intervention arm), and their overall satisfaction with the research element of the therapy (both arms), and also to give written comment on their answers to each questions and any general comments on the therapy or research. A brief feedback questionnaire will be sent to those exiting the study early, at the point they exit, if they have indicated they would be willing to complete this.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo monitor and evaluate intervention and study safety an \u0026lsquo;Asking about adverse events\u0026rsquo; form will be completed following the intake assessment (a researcher will check on participants\u0026rsquo; wellbeing within a week of the intake assessment), and at the 14-, 30- and 52- week follow-up points. Members of the research team will also follow up with participants in relation to any potential adverse events mentioned in ad-hoc communications, therapy contacts or via HEQ completion.\u003c/p\u003e\n\u003cp\u003eParticipants will be invited to rank outcome measures according to which they would most wish to experience change upon. Rankings will be conducted at baseline, and at the 30-week follow-up point.\u003c/p\u003e\n\u003cp\u003eParticipants will be asked about their concordance with their prescribed psychiatric medication using the single, overall compliance question from the Brief Adherence Rating Scale (BARS [48]) at intake, 14 and 30 weeks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQualitative interview\u003c/p\u003e\n\u003cp\u003eAt 30 weeks (patient participants) and at the end of the trial (therapists) there will be audio-recorded qualitative interviews of approximately 60 minutes conducted by one of the research team exploring experiences of the therapy. Fifteen participants in the intervention arm, purposively sampled to span diversity in terms of demographic characteristics and outcome in terms of therapy attendance, will be interviewed. All therapists who have delivered at least one therapy session as part of the study will be invited to be interviewed.\u003c/p\u003e\n\u003cp\u003eThe interview will allow participants / therapists to describe their views in detail. The interview will be informed by the topic areas highlighted in process evaluation guidance [49], namely fidelity and quality of intervention implementation, mechanisms of change and impact of context. Specifically, it will ask about how participants / therapists found the therapy, any perceived effects of the therapy, aspects that were helpful / unhelpful, and views on the length and delivery format of the treatment and the feasibility/acceptability of both the intervention and the outcome measurement (for participants). It will also ask about experienced process of change, including questions on hypothesised mechanisms but also leaving space for these to arise inductively from reports, as well as participants\u0026rsquo; experiences of the impact of the context in which they received the intervention (their personal / social context, and the healthcare context). The interviews will follow a topic guide, but with flexibility to adapt this based on the answers given.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData collection forms will be available on request from the Chief Investigator following completion of the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProcedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent will be taken prior to or at commencement of the eligibility assessment by a member of the study team; consent will be re-affirmed verbally prior to qualitative interviews. Following the initial eligibility assessment and completion of baseline measures participants will be randomised to either STABILISE plus TAU, or TAU. Those allocated to the intervention arm will commence treatment approximately 2 weeks after being deemed eligible. Assessments at 14, 30 and 52 weeks will involve participants completing self-report measures either online or on paper, according to their preference, as well as speaking to a member of the research team (online, by telephone or in person) to complete the measures that require contemporaneous researcher involvement. A default procedure will be followed in cases where participants do not respond to requests to complete measures, with the procedure being tailored in accordance with individual patient preferences, as discussed following acceptance to the study. Figure 1 displays the measures completed at each time point.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the feasibility design, data analysis will focus on a descriptive analysis of the feasibility objectives of the study. Participant characteristics at baseline will be reported descriptively for each treatment group, using mean (SD) for continuous variables, and percentages for categorical variables. Outcome measures will be reported descriptively for each treatment group at baseline and at each post-randomisation follow-up, i.e. 14, 30 and 52 weeks. For 30- and 52-week follow-up data, the between group mean differences for continuous variables (intervention minus control group) will be reported with a 95% CI. Given the feasibility nature of the trial, all participants will be analysed according to their randomised group irrespective of treatment actually received. Analyses will include observed data only; no imputation of missing outcome data will be performed. Analyses will be performed using Stata v18 or later, by a statistician who is blinded to group allocation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEconomic analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe economic analyses will follow the same approach as the statistical analysis. We will use an intention-to-treat analysis, taking the NHS and social care perspective. As this is a feasibility trial, we will report descriptive data only for each trial arm, with confidence intervals for between group comparisons. No \u003cem\u003ep\u003c/em\u003e-values will be reported. Primary analysis will be based on complete case data. However, losses to follow-up at data collection points will be presented for both primary and secondary outcomes. Missing outcome data will also be discussed, along with its causes.\u003c/p\u003e\n\u003cp\u003eIn order to cost the intervention, we will collect information on the resource use and costs of delivering the STABILISE intervention depending the type of delivery i.e.,\u0026nbsp;face-to-face, online or by phone. It will include costs on training and salaries, course materials, travel expenses, supervision and administration costs. The costs of the intervention will be estimated as a cost per participant.\u0026nbsp;Sensitivity analyses will be conducted using the minimum and maximum number of sessions of the STABILISE intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQualitative data analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQualitative interviews will be audio-recorded and then transcribed. Participants\u0026rsquo; responses will be read closely and coded using a framework approach, informed by the framework for assessing intervention acceptability proposed by Sekhon and colleagues [50]. Data relevant to each category will be compared and summarised and non-conforming cases examined closely to understand similarities and differences in perspective. Interview recordings will be transcribed by a member of the study team, or a suitable individual working with the team who has signed a confidentiality agreement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Management and Storage\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformation gathered electronically will make use of data capture platforms that conform to U.K. NHS data governance standards. Information will be stored according to standard practice within the NHS services hosting the intervention. Hard copies of information / measures gathered as part of this research study will be anonymised and stored in a locked filing cabinet in a locked office in the Department of Psychology, University of Exeter or a locked cabinet in a locked office on local participating NHS Trust premises. Participants will be identified by a code, with the document linking participant name with ID code being stored separately to the rest of the data, and accessible only to measures of the research team. Consent forms will be stored in a locked cabinet separately to data. Audio recordings will be recorded directly to, or immediately transferred in digital form to, a secure data storage area hosted by the University of Exeter (Secure Data Research Hub: SDRH). Personal data will be transferred and stored only where necessary.\u003c/p\u003e\n\u003cp\u003eStudy data will be stored in linked-anonymous form. General Data Protection Regulation (2018) will be followed, and the NHS services providing therapy will abide by the Information Governance requirements of their service. Within NHS services providing the therapy, participant information will not be stored anonymously as it will form part of the patient record.\u003c/p\u003e\n\u003cp\u003eAt the end of the study any anonymised paper data will be scanned into electronic form or entered into electronic databases (if not already done) and stored securely in the secure data storage area of the University of Exeter and the original paper copies and audio-recordings destroyed confidentially. The project CI will act as custodian for the data. If the CI leaves employment of the University of Exeter, a data custodian will be appointed by the University of Exeter (a member of the research group or of Exeter IT Services) who will manage continued archiving of the data. Anonymised data will be retained for 20 years. Personally identifiable information will be stored for 12 months after the end of the study to enable sufficient time for the study data to be analysed and a summary of the results to be sent to participants who requested these at study entry.\u003c/p\u003e\n\u003cp\u003eClinical data gathered as part of the individual\u0026rsquo;s treatment within the clinical services hosting the therapy will be stored according to local protocols on the retention of NHS clinical records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study team members will have access to the final dataset, with the agreement of the CI.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent will be sought from participants to share anonymised data with other researchers for secondary analyses. Because of the potentially sensitive nature of the data and the potential for participants to be identifiable by their data by some members of the public, the public will not be given unrestricted access to the data. In accordance with good practice and institutional policy the research database will be registered with the University of Exeter public access database. The dataset will be anonymous and will be registered with a metadata only record, allowing the research team to control access to the dataset, restricting it to appropriately qualified third parties.\u003c/p\u003e\n\u003cp\u003eData captured on paper will be entered by a member of the research team and checked by a second member of the team. Databases containing data returned by paper and through electronic data capture systems will be merged with assistance from Exeter Clinical Trials Unit prior to data analysis. Range checks will be used to help identify erroneous datapoints prior to analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Approvals\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe conduct of the trial will be in accordance with the Helsinki Declaration. The study has received approval from the U.K. Health Research Authority Research Ethics Service (IRAS ID: 335983), and from all relevant local approval bodies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnticipated Risks and Benefits\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe administration of a novel therapeutic intervention raises the potential of risk to those in the trial, as well as potential benefit. We believe that the intervention is unlikely to pose significant risks: the approach is an adaptation of two widely used existing therapies (Behavioural Activation and Dialectical Behavioural Therapy), both of which have been delivered previously by our team to people with bipolar disorder in case series and trial contexts with no significant concerns about therapy safety resulting [18,25]. We are currently completing a case series evaluation of the STABILISE approach: at the time of writing all 12 participants have completed the acute phase of therapy with no significant concerns arising regarding the safety of the intervention. Reactions to therapy will be monitored by therapists and within clinical supervision and standard operating procedures relating to monitoring and reporting adverse events will be followed.\u003c/p\u003e\n\u003cp\u003eIn this study participants are allocated at random to receive either TAU, or TAU plus the novel intervention. Therefore, there is a risk that a participant may be disappointed by allocation to the former arm. The inclusion of a treatment as usual comparator arm is necessary in order to address some of the feasibility aims (to establish the acceptability of procedures to be used in a definitive trial, including randomisation). Participants will be informed of the nature and purpose of the randomisation element. They will be called by an unblinded member of the study team to inform them of their allocation; their response to this will be monitored including the offer of a follow-up call the following day. Participants in both arms will be directed towards sources of support in the local community and nationally. It will be made clear to those in the usual care arm that whilst participants currently receiving psychological therapy for bipolar disorder will not be eligible to join the study, no restrictions are placed on the treatments that participants can choose to access outside of the study whilst they are a part of it. Because the treatment is experimental it is not currently planned that it will be routinely offered to trial participants following study completion.\u003c/p\u003e\n\u003cp\u003eThere is a chance that completion of study measures may induce distress. Our experience of using similar methods in previous research projects is that a significant adverse reaction is rare and if it occurs it is transient. The information sheet will make clear to participants that filling in the measures may temporarily lower mood or cause distress. The therapist/researcher will ask participants if they suffer any adverse reaction completing measures and will follow service or research distress management protocols if a significant level of distress is observed. Participants will be contacted within a week of completing the initial assessment to check on their welfare and to develop a bespoke plan for supporting participants as they move through the study (e.g. texts to check in with them, occasional planned calls, etc).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe sponsor holds indemnity policies to allow compensation of trial participants if formal claims of harm are made and upheld.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse Events\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe will monitor and record both serious and non-serious adverse events. Adverse event reports will be solicited at follow-up points and monitored during all research contacts and through inspection of HEQ responses. An adverse event (AE) is defined by the HRA as any untoward occurrence or worsening of an unintended sign, symptoms or disease that occurs during participation, regardless of any relation to participation. In the STABILISE study, an adverse event will be recorded only when medical / clinical assessment or treatment is sought for a new or worsening sign, symptom or disease, unless the event appears to be a result of participation in the study. \u0026nbsp;An adverse event will be classified as serious if it results in: death, life threatening injury or condition, permanent impairment to a body structure, body function or the capacity of the individual to function in daily life; hospitalisation or extension of existing hospitalisation; foetal death, or a congenital abnormality or birth defect.\u003c/p\u003e\n\u003cp\u003eSymptoms of Bipolar Disorder themselves are not defined as adverse events. However, deterioration in mental state that results in the person accessing emergency support will be classed as an adverse event.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAny AEs that researchers or therapists believe may be study related, may merit a classification of \u0026ldquo;severe\u0026rdquo; (even if not technically meeting SAE criteria), or may constitute an SAE will be required to be reported to the site PI, Trial Manager and the CI within 24 hours. Other AEs must be reported to the PI, Trial Manager and CI within one week.\u0026nbsp;The reporting period for all events and reactions will be from intake assessment to completion of the 52 week follow-up point.\u003c/p\u003e\n\u003cp\u003eThe only expected reactions to the therapy and / or trial procedures are distress or symptom exacerbation (including behaviours such as self-harm, suicidal behaviour or substance use which may be considered to be part of the symptom set that individual typically experiences or may be considered to be coping responses in the face of distress or symptom exacerbation).\u003c/p\u003e\n\u003cp\u003eIt is recognised that those participants in the intervention arm have more contact with the study team (and therefore more opportunity to report adverse events) than do those in the usual care arm, by virtue of attending therapy sessions. Thus, we may expect a higher rate of adverse events reported in the former arm. In this study particular attention will be paid to those events that appear to be caused by research or therapy participation.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eCriteria for Discontinuation\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eIndividual participants will discontinue their involvement if either: i) the participant does not wish to continue with the intervention and study; ii) the participant experiences an unexpected serious adverse reaction (mental or physical health event that results in significant impairment, hospitalisation or death) that is judged to be the direct result of the intervention or trial participation, where discontinuation is judged to be in the best interests of the participant by the participant or sponsor (with advice from the Trial Steering Committee); iii) the participant and / or therapy / research team believe that the intervention or trial participation will result in, or is likely to result in, a serious adverse reaction if continued; iv) the participant does not attend more than three consecutive therapy sessions without explanation; this will be judged to indicate discontinuation of therapy. Over the period that the participant does not attend sessions, efforts will be made by the therapist to contact the participant. Participant choice to discontinue therapy will not be assumed to mean automatic withdrawal from the trial.\u003c/p\u003e\n\u003cp\u003eShould an unexpected serious adverse reaction occur to either the therapy or the trial procedures, and this is judged to be directly related to trial participation or to the therapy, the trial will be temporarily halted pending investigation and analysis of the extent to which future risk can be mitigated against. If it is judged that this is not possible, the trial will be discontinued. This process will be led by the sponsor in collaboration with the TSC chair and CI. Should information come to light from external sources that indicates that the therapy intervention or trial procedures are unsafe, the same process will be followed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and Public Involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThroughout this study we are working with a patient and public involvement panel (PPI panel) of individuals with personal experience of bipolar disorder, or who have a relative with bipolar disorder. The panel have contributed to the design of the therapy protocol and the materials for patients such as the information sheet, consent form and interview topic guide; a subgroup contributed to the initial design of the study itself. The panel will advise on the running of this study throughout.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Governance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Trial Steering Committee (TSC) includes independent members with academic and / or clinical expertise, and / or expertise based on personal experience. Also included are the CI and trial statistician. The TSC will meet approximately five times over the life of the project and will be responsible for advising the trial team on the conduct of the study. Given the relatively small scale of the trial a separate Data Monitoring Committee (DMC) has not been convened. Instead, the DMC functions (reviewing data collected including adverse events and making recommendations for the future conduct of the trial) are included within the terms of reference of the TSC.\u003c/p\u003e\n\u003cp\u003eApproval will be sought from the sponsor and the relevant national regulatory bodies for all substantive changes to the protocol and these will be communicated externally via an update to the ISRCTN registration record.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the Funder and Sponsor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUltimate authority over the management of the study lies with the study sponsor. Neither the funder nor the sponsor of the study were involved in the design of the study and will not be involved in the collection, analysis or interpretation of data, or the writing of the study report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data arising from the study will be the property of the University of Exeter and the Chief Investigator. On completion of the study, the data will be analysed and tabulated and a Final Study Report prepared. The full study report will be made available in open access form via the University of Exeter and publication via a peer reviewed journal will be sought, acknowledging contributions to the study in line with journal policy. Findings will also be disseminated through academic conference presentations or posters, and publicly following a dissemination strategy to be developed with the PPI panel. Participants will be asked to state whether they wish to receive a copy of the findings which they will be sent once these have been finalised. In order to protect participant anonymity, the raw data will not be made publicly accessible.\u003c/p\u003e\n\u003cp\u003eAuthorship of the final trial report will be in line with the recommendations of the International Committee of Medical Journal Editors [51].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe start date of the trial was 28\u003csup\u003eth\u003c/sup\u003e March 2024. Recruitment is running from April 2024 to June 2025 inclusive. Follow up will last 52 weeks, with the entire study period lasting for 28 months.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003eExpected findings\u003c/h2\u003e \u003cp\u003eThis trial is designed to assess the feasibility, acceptability and safety of a randomised controlled trial of an adapted form of behavioural therapy for individuals with ongoing bipolar symptoms or cyclothymic disorder. To do so we will employ a mixed-methods approach whereby information about intervention acceptability is derived both from quantitative measures of attendance and completion and participant acceptability ratings, as well as from qualitative information gathered via interview and feedback questionnaire. Our study builds on an intervention co-development phase with individuals with lived experience of bipolar disorder, and also upon a case series in which 12 people received the resulting intervention. The case series met pre-determined continuation criteria, allowing progression to the current trial to address uncertainties prior to conducting a definitive, randomised, controlled trial of the intervention. Progression to the definitive trial will be determined according to performance against the set of continuation criteria described here.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec28\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eAs this is a feasibility trial it is not designed to assess the clinical effectiveness of the intervention. Whilst this study will benefit from the information provided by the inclusion of a second trial site, the feasibility conclusions drawn may not apply to all possible additional sites in a future definitive trial. Consequently planning and decision-making with respect to any future trial will take into account additional information available, outside of the scope of the current study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study is an early step in establishing the clinical and cost effectiveness of an adapted form of behavioural therapy for people who find their bipolar mood issues persist outside of major affective episodes. In the longer term, if effectiveness is demonstrated, the intention is that it could be routinely delivered within the U.K. health service.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eAE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eAdverse Event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eALS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eAffective Lability Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eASRM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eAltman Scale for Rating Mania\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBehavioural Activation therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBADS-SF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBehavioral Avoidance in Depression Scale \u0026ndash; Short Form\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBARS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBrief Adherence Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBipolar Disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBDI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBeck Depression Inventory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eBRQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eBipolar Recovery Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eChief Investigator\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eDBT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eDialectical Behaviour Therapy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eDSM-V\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eDiagnostic and Statistical Manual of Mental Disorders, fifth edition\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eEQ-5D-5L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eEuroQoL 5 Dimension 5 Level\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eGAD-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eGeneralised Anxiety Disorder 7-item scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eHAM-D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eHamilton Depression Rating Scale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eHEQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eHealth Economics Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eICD-11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eInternational Classification of Diseases 11\u003csup\u003eth\u003c/sup\u003e Revision\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eIEBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eInter-episode bipolar symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eNHS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eU.K. National Health Service\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eNIHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eNational Institute for Health Research\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePHQ-9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003ePatient Health Questionnaire 9 item scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePPI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003ePatient and Public Involvement\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eQALYS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eQuality Adjusted Life Years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eQoL-BD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eQuality of Life in Bipolar Disorder scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eSAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eSerious adverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eSCID-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eStructured clinical interview for DSM-V\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eStandard Deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eSTABILISE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eExperimental treatment evaluated in this study\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTAU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eTreatment as usual\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eTSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003eTrial Steering Committee\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003ePU \u0026amp; NU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003ePositive and Negative Urgency Scales\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 473px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has received approval from the U.K. Health Research Authority Research Ethics Service (IRAS ID: 335983), and from all relevant local approval bodies. Potential participants will receive full information about the study before giving consent and will have opportunity at the screening call, and before and during the intake assessment, to ask questions and discuss the study. Researchers will be fully trained in taking informed consent, including assessment of capacity to consent where appropriate. Consent will be taken only from individuals with capacity to make an informed decision on their participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKim Wright occasionally receives payment in addition to her usual salary for delivery of workshops on psychological interventions for bipolar disorder to academic and healthcare organisations.\u0026nbsp;Sandra Bucci is a director and shareholder of CareLoop\u0026nbsp;Health Ltd, a University of Manchester start-up to develop and market digital solutions for mental health problems, currently in schizophrenia and postnatal depression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial described by this protocol is funded by the National Institute for Health Research Advanced Fellowship Programme (ref: NIHR 302220) awarded to Kim Wright.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSB discloses support for publication of this work from a\u0026nbsp;National Institute for Health and Care Research research professorship (NIHR300794) and the NIHR Manchester Biomedical Research Centre (NIHR 203308).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the conception and design of the study protocol. KW drafted the manuscript and all other authors contributed to the editing of the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study is supported by the UK Clinical Research Network with respect to participant recruitment, and by the University of Exeter Clinical Trials Unit with respect to trial management, database integration and randomisation. We would like to thank Prof Judit Simon and Dr Susanne Mayer for permission to use the HEQ.\u003c/p\u003e\n\u003cp\u003eThe study is sponsored by the University of Exeter, Stocker Road, Exeter EX4 4PY, U.K.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePini S, De Queiroz V, Pagnin D, Pezawas L, Angst J, Cassano GB, Wittchen HU. Prevalence and burden of bipolar disorders in European countries. European Neuropsychopharmacology. 2005 Aug 1;15(4):425-34.\u003c/li\u003e\n\u003cli\u003eSimon J, Pari AA, Wolstenholme J, Berger M, Goodwin GM, Geddes JR. The costs of bipolar disorder in the United Kingdom. Brain and Behavior. 2021 Oct;11(10):e2351.\u003c/li\u003e\n\u003cli\u003ePaykel ES, Abbott R, Morriss R, Hayhurst H, Scott J. Sub-syndromal and syndromal symptoms in the longitudinal course of bipolar disorder. The British Journal of Psychiatry. 2006 Aug;189(2):118-23.\u003c/li\u003e\n\u003cli\u003eMacQueen GM, Marriott M, Begin H, Robb J, Joffe RT, Young LT. Subsyndromal symptoms assessed in longitudinal, prospective follow‐up of a cohort of patients with bipolar disorder. Bipolar Disorders. 2003 Oct;5(5):349-55.\u003c/li\u003e\n\u003cli\u003eGershon A, Eidelman P. Inter-episode affective intensity and instability: predictors of depression and functional impairment in bipolar disorder. Journal of Behavior Therapy and Experimental Psychiatry. 2015 Mar 1;46:14-8.\u003c/li\u003e\n\u003cli\u003eKochman FJ, Hantouche EG, Ferrari P, Lancrenon S, Bayart D, Akiskal HS. Cyclothymic temperament as a prospective predictor of bipolarity and suicidality in children and adolescents with major depressive disorder. Journal of affective disorders. 2005 Mar 1;85(1-2):181-9.\u003c/li\u003e\n\u003cli\u003eSamalin L, de Chazeron I, Vieta E, Bellivier F, Llorca PM. Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder. Bipolar disorders. 2016 Mar;18(2):164-73.\u003c/li\u003e\n\u003cli\u003eRoux P, Raust A, Cannavo AS, Aubin V, Aouizerate B, Azorin JM, Bellivier F, Belzeaux R, Bougerol T, Cussac I, Courtet P. Associations between residual depressive symptoms, cognition, and functioning in patients with euthymic bipolar disorder: results from the FACE-BD cohort. The British Journal of Psychiatry. 2017 Dec;211(6):381-7.\u003c/li\u003e\n\u003cli\u003eStanislaus S, Faurholt-Jepsen M, Vinberg M, Coello K, Kjaerstad HL, Melbye S, Sletved KS, Christensen EM, Frost M, Bardram JE, Kessing LV. Mood instability in patients with newly diagnosed bipolar disorder, unaffected relatives, and healthy control individuals measured daily using smartphones. Journal of Affective Disorders. 2020 Jun 15;271:336-44.\u003c/li\u003e\n\u003cli\u003eJudd LL, Schettler PJ, Akiskal HS, Coryell W, Leon AC, Maser JD, Solomon DA. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Archives of general psychiatry. 2008 Apr 1;65(4):386-94.\u003c/li\u003e\n\u003cli\u003eAlda M, McKinnon M, Blagdon R, Garnham J, MacLellan S, O\u0026apos;Donovan C, Hajek T, Nair C, Dursun S, MacQueen G. Methylene blue treatment for residual symptoms of bipolar disorder: randomised crossover study. The British Journal of Psychiatry. 2017 Jan;210(1):54-60.\u003c/li\u003e\n\u003cli\u003eYilmaz S, Huguet A, Kisely S, Rao S, Wang J, Baur K, Price M, O\u0026apos;Mahen H, Wright K. Do psychological interventions reduce symptoms of depression for patients with bipolar I or II disorder? A meta-analysis. Journal of affective disorders. 2022 Mar 15;301:193-204.\u003c/li\u003e\n\u003cli\u003eMazzarini L. The treatment of cyclothymia. The Treatment of Bipolar Disorder: Integrative Clinical Strategies and Future Directions. 2017 Feb 9:123.\u003c/li\u003e\n\u003cli\u003eCiharova M, Furukawa TA, Efthimiou O, Karyotaki E, Miguel C, Noma H, Cipriani A, Riper H, Cuijpers P. Cognitive restructuring, behavioral activation and cognitive-behavioral therapy in the treatment of adult depression: A network meta-analysis. Journal of Consulting and Clinical Psychology. 2021 Jun;89(6):563.\u003c/li\u003e\n\u003cli\u003eCuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta‐analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020 Feb;19(1):92-107.\u003c/li\u003e\n\u003cli\u003eRichards DA, Ekers D, McMillan D, Taylor RS, Byford S, Warren FC, Barrett B, Farrand PA, Gilbody S, Kuyken W, O\u0026apos;Mahen H. Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial. The Lancet. 2016 Aug 27;388(10047):871-80.\u003c/li\u003e\n\u003cli\u003eWeinstock LM, Melvin C, Munroe MK, Miller IW. Adjunctive behavioral activation for the treatment of bipolar depression: a proof of concept trial. Journal of Psychiatric Practice. 2016 Mar 1;22(2):149-58.\u003c/li\u003e\n\u003cli\u003eWright, K., Mostazir, M., Bailey, E., Dunn, B. D., O\u0026rsquo;Mahen, H., Sibsey, M., \u0026amp; Thomas, Z. (2022). Adapted Behavioural Activation for Bipolar Depression: A Randomised Multiple Baseline Case Series. \u003cem\u003eBrain Sciences\u003c/em\u003e, \u003cem\u003e12\u003c/em\u003e(10), 1407.\u003c/li\u003e\n\u003cli\u003eLinehan M. Cognitive-behavioral treatment of borderline personality disorder. Guilford press; 1993 May 14.\u003c/li\u003e\n\u003cli\u003eSwales MA, Dunkley C. Structuring the Wider Environment and the DBT Team. The Oxford Handbook of Dialectical Behaviour Therapy. 2018 Oct 25:217.\u003c/li\u003e\n\u003cli\u003eDeCou CR, Comtois KA, Landes SJ. Dialectical behavior therapy is effective for the treatment of suicidal behavior: A meta-analysis. Behavior therapy. 2019 Jan 1;50(1):60-72.\u003c/li\u003e\n\u003cli\u003eHaktanır A, Callender KA. Meta-analysis of dialectical behavior therapy (DBT) for treating substance use. Research on education and psychology. 2020;4(Special Issue):74-87.\u003c/li\u003e\n\u003cli\u003eCiesinski NK, Sorgi-Wilson KM, Cheung JC, Chen EY, McCloskey MS. The effect of dialectical behavior therapy on anger and aggressive behavior: A systematic review with meta-analysis. Behaviour research and therapy. 2022 Jul 1;154:104122.\u003c/li\u003e\n\u003cli\u003eJones BD, Umer M, Kittur ME, Finkelstein O, Xue S, Dimick MK, Ortiz A, Goldstein BI, Mulsant BH, Husain MI. A systematic review on the effectiveness of dialectical behavior therapy for improving mood symptoms in bipolar disorders. International Journal of Bipolar Disorders. 2023 Feb 5;11(1):6.\u003c/li\u003e\n\u003cli\u003eWright K, Dodd AL, Warren FC, Medina-Lara A, Dunn B, Harvey J, Javaid M, Jones SH, Owens C, Taylor RS, Duncan D. Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme). International Journal of Bipolar Disorders. 2021 Dec;9:1-3.\u003c/li\u003e\n\u003cli\u003eHerdman M, Gudex C, Lloyd A, Janssen MF, Kind P, Parkin D, Bonsel G, Badia X. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Quality of life research. 2011 Dec;20:1727-36.\u003c/li\u003e\n\u003cli\u003eAvery KN, Williamson PR, Gamble C, Francischetto EO, Metcalfe C, Davidson P, Williams H, Blazeby JM. Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies. BMJ open. 2017 Feb 1;7(2):e013537.\u003c/li\u003e\n\u003cli\u003eKahan BC, Hindley J, Edwards M, Cro S, Morris TP. The estimands framework: a primer on the ICH E9 (R1) addendum. bmj. 2024 Jan 23;384.\u003c/li\u003e\n\u003cli\u003eAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013.\u003c/li\u003e\n\u003cli\u003eFirst MB, Williams JB, Karg RS, Spitzer RL. Structured Clinical Interview for DSM-5 Disorders\u0026ndash;Research Version (SCID-5-RV). Arlington: American Psychiatric Assocation. 2014.\u003c/li\u003e\n\u003cli\u003eOliver MN, Simons JS. The affective lability scales: Development of a short-form measure. Personality and individual differences. 2004 Oct 1;37(6):1279-88.\u003c/li\u003e\n\u003cli\u003eKroenke K, Spitzer RL, Williams JB. The PHQ‐9: validity of a brief depression severity measure. Journal of general internal medicine. 2001 Sep;16(9):606-13.\u003c/li\u003e\n\u003cli\u003eHamilton M. A rating scale for depression. Journal of neurology, neurosurgery, and psychiatry. 1960 Feb;23(1):56.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. \u003cem\u003eICD-11:\u003c/em\u003e \u003cem\u003eInternational classification of diseases \u003c/em\u003e(11th revision). 2022.\u003c/li\u003e\n\u003cli\u003eJulious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics: The Journal of Applied Statistics in the Pharmaceutical Industry. 2005 Oct;4(4):287-91.\u003c/li\u003e\n\u003cli\u003eWhitehead AL, Julious SA, Cooper CL, Campbell MJ. Estimating the sample size for a pilot randomised trial to minimise the overall trial sample size for the external pilot and main trial for a continuous outcome variable. Statistical methods in medical research. 2016 Jun;25(3):1057-73.\u003c/li\u003e\n\u003cli\u003eFylan B, Tomlinson J, Raynor DK, Silcock J. Using experience-based co-design with patients, carers and healthcare professionals to develop theory-based interventions for safer medicines use. Research in Social and Administrative Pharmacy. 2021 Dec 1;17(12):2127-35.\u003c/li\u003e\n\u003cli\u003eBeck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Archives of general psychiatry. 1961;4:561-71.\u003c/li\u003e\n\u003cli\u003eAltman EG, Hedeker D, Peterson JL, Davis JM. The Altman self-rating mania scale. Biological psychiatry. 1997 Nov 15;42(10):948-55.\u003c/li\u003e\n\u003cli\u003eMichalak EE, Murray G, CREST. BD. Development of the QoL. BD: a disorder‐specific scale to assess quality of life in bipolar disorder. Bipolar disorders. 2010 Nov;12(7):727-40.\u003c/li\u003e\n\u003cli\u003eJones S, Mulligan LD, Higginson S, Dunn G, Morrison AP. The bipolar recovery questionnaire: psychometric properties of a quantitative measure of recovery experiences in bipolar disorder. Journal of affective disorders. 2013 May 31;147(1):34-43.\u003c/li\u003e\n\u003cli\u003eSpitzer RL, Kroenke K, Williams JB, L\u0026ouml;we B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Archives of internal medicine. 2006 May 22;166(10):1092-7.\u003c/li\u003e\n\u003cli\u003eBech P, Rafaelsen OJ, Kramp P, Bolwig TG. The mania rating scale: scale construction and inter-observer agreement. Neuropharmacology. 1978 Jun 1;17(6):430-1.\u003c/li\u003e\n\u003cli\u003eJacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology. 1991; 59:12-19. \u003c/li\u003e\n\u003cli\u003eSimon, J, Mayer, S. HEQ (Health Economics Questionnaire), Version 08-09-2016. Vienna: Department of Health Economics, Center for Public Health, Medical University of Vienna. 2016.\u003c/li\u003e\n\u003cli\u003eCyders MA, Smith GT, Spillane NS, Fischer S, Annus AM, Peterson C. Integration of impulsivity and positive mood to predict risky behavior: development and validation of a measure of positive urgency. Psychological assessment. 2007 Mar;19(1):107.\u003c/li\u003e\n\u003cli\u003eManos RC, Kanter JW, Luo W. The behavioral activation for depression scale\u0026ndash;short form: development and validation. Behavior therapy. 2011 Dec 1;42(4):726-39.\u003c/li\u003e\n\u003cli\u003eByerly MJ, Nakonezny PA, Rush AJ. The Brief Adherence Rating Scale (BARS) validated against electronic monitoring in assessing the antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. Schizophrenia research. 2008 Mar 1;100(1-3):60-9.\u003c/li\u003e\n\u003cli\u003eSkivington K, Matthews L, Simpson SA, Craig P, Baird J, Blazeby JM, Boyd KA, Craig N, French DP, McIntosh E, Petticrew M. A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance. bmj. 2021 Sep 30;374.\u003c/li\u003e\n\u003cli\u003eSekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC health services research. 2017 Dec;17:1-3.\u003c/li\u003e\n\u003cli\u003eInternational Committee of Medical Journal Editors. Defining the role of authors and contributors. Cited 2024 June 19. Available from: https://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pilot-and-feasibility-studies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pafs","sideBox":"Learn more about [Pilot and Feasibility Studies](http://pilotfeasibilitystudies.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/PAFS/default.aspx","title":"Pilot and Feasibility Studies","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bipolar Disorder, Cyclothymic Disorder, behavioural therapy, psychological therapy, interepisode symptoms","lastPublishedDoi":"10.21203/rs.3.rs-5223139/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5223139/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eIn between episodes of (hypo) mania and major depression, people with bipolar disorder can experience ongoing low mood or mood instability, and these may also be present as part of cyclothymic disorder. This is a phase II evaluation of an adapted form of behavioural therapy (STABILISE) for inter-episode bipolar symptoms. The study aims to establish the feasibility and acceptability of the therapy and research procedures, including an economic component, to inform a future definitive trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePatients will be randomised 1:1 to either Treatment as Usual (control arm) or Treatment as Usual plus STABILISE intervention (intervention arm). Follow up points will be at 14, 30 and 52 weeks post eligibility confirmation, with 30 weeks as the primary end point. We aim to recruit 60 individuals meeting diagnostic criteria for a Bipolar Spectrum Disorder, and reporting ongoing bipolar symptoms (low mood or mood instability) outside of a manic or severe depressive episode. Feasibility and acceptability will be examined through recruitment and retention rates, completion rates for the candidate primary outcome measures (PHQ9, ALS-SF, QoL.BD and BRQ) and feedback from participants on their experience of study participation and therapy. Proceeding to a definitive trial will be indicated if the following criteria are met: i) trial participation is deemed, or can be made, sufficiently safe; ii) recruitment rate indicates that larger-scale recruitment would be feasible (recruitment rate of at least two participants per month within at least one site, with mitigation plan if overall target sample size not met); iii) for candidate primary outcome measure follow up data is available at 30 weeks from at least 75% of participants, or from between 55 and 74% with clear plan for improvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThis study is a randomised, controlled feasibility trial that builds on an initial case series of the STABILISE approach. The findings will be used to establish whether a future, definitive trial is feasible and to refine the research procedures and therapy protocol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e: ISRCTN18207465. 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