An integrated COgnitive-somatoSensory-MOtor training intervention for upper limb recovery after stroke: Protocol for a Phase II randomized controlled trial

An integrated COgnitive-somatoSensory-MOtor training intervention for upper limb recovery after stroke: Protocol for a Phase II randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article An integrated COgnitive-somatoSensory-MOtor training intervention for upper limb recovery after stroke: Protocol for a Phase II randomized controlled trial Urvashy Gopaul, Laura Langer, Mark Bayley This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6206942/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Up to 85% of stroke survivors experience motor, somatosensory and cognitive deficits. Interventions that simultaneously stimulate motor, somatosensory and cognitive functions have the potential to maximize processes of neuroplasticity and optimise upper limb recovery after stroke. This study aims to investigate the feasibility of a personalised integrated COgnitive-somatoSensory-MOtor (iCOSMO) training intervention to improve upper limb recovery in people with chronic stroke. The objectives are: 1) to evaluate the feasibility, and 2) to determine the preliminary efficacy of the iCOSMO intervention in people with chronic stroke. Methods: The study design will be a prospective pilot randomised controlled trial with two-arms. We aim to recruit 40 adults with stroke (>6 months). The iCOSMO intervention will consist of a combination of haptic perception exploratory tasks that incorporate active touch and movement exploratory procedures, robotic training using the Kinarm Exoskeleton device, with a cognitive focus on the motor and sensory attributes of all of the tasks. iCOSMO will be goal-oriented and individualised to the nature and severity of upper limb somatosensory and motor deficits. The experimental group will receive a total of 36 hours of treatment over 6 weeks. The control group will receive a matched dose of a Graded Repetitive Arm Supplementary Program home-based motor exercise programme. Feasibility measures will evaluate the recruitment and adherence rates. Robotic assessments will be conducted using the Kinarm standard tasks™. Standardised clinical assessments will include the Action Research Motor Test and the Tactile Discrimination Test. Conclusion: This study will be the first to demonstrate whether it is both feasible and beneficial to deliver a personalised intervention integrating somatosensory, motor and cognitive training in one protocol. The iCOSMO study may also show that it is feasible to individualise the intervention tasks to the nature and severity of upper limb deficits. It is also expected that the iCOSMO training intervention will improve the arm and hand function to a larger extent than the GRASP training in chronic stroke survivors. This proposed study will help better understand the impact of combining cognitive, somatosensory, and motor training in task performance. Trial registration: This trial was prospectively registered on Clinicaltrial.gov (NCT06498011) on July, 12th, 2024 and is available at https://clinicaltrials.gov/study/NCT06498011 Stroke motor somatosensation upper limbs randomized controlled trial Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 BACKGROUND Stroke is one of the leading causes of disability in Canada and around the world. Upper limb impairments after stroke are the primary cause of functional limitations 1 . More than 85% of stroke survivors suffer from residual upper limb movement deficits due to incomplete motor recovery 2 , and one in two stroke survivors have deficits in somato (body) sensations 3 . Similarly, up to 44% of stroke survivors experience cognitive impairments 4 . Both somatosensory and motor function are essential in the performance of daily activities using the upper limbs. Motor, somatosensory, and cognitive function are all integrated and tightly coupled in action in everyday life 5 . It is hypothesized that improvement in cognitive function could enhance both somatosensory and motor function after stroke. Previous work has shown benefits associated with observation training prior to completing a motor task after stroke, indicating there is a link with cognitive training and motor performance 6 . So far, cognitive training has rarely been combined with either somatosensory or motor training in stroke rehabilitation. Only one study by Chanubol et al. investigated the effects of cognitive sensory motor training therapy using the Perfetti method. This focused on retraining of sensory guided motor control, with particular emphasis on joint position perception 7 . Cognitive training using the Kinarm robotic exoskeleton (Kinarm, Kingston, Ontario) can also help improve cognitive-sensory function 8 , which in turn has impacts on somatosensory and motor function. So far, there has been no intervention to combine somatosensory, motor, and cognitive training in an integrated manner within the same protocol to improve upper limb function after stroke. Hence, there is a critical need for the development of new, more effective treatments. The theoretical underpinning behind this intervention is the work completed by Filmer, Mattingley, Marois, and Dux in 2013. By disrupting prefrontal cortex activity using transcranial direct current stimulation, performance gains in a somatosensory-motor task were prevented 9 . Our group inferred that if disruptions to cognitive function impair sensory-motor function, then improvements in cognitive function through training would likely heighten somatosensory-motor performance. Additionally, tailoring of the active ingredients and dosage parameters of an intervention towards the participants’ characteristics with regards to the nature and severity of deficits is critical. This reinforces a personalised training approach according to the needs of the participant, which is recommended in rehabilitation trials post-stroke 10 . The proposed novel intervention combines cognitive, somatosensory, and motor training in an integrated manner which is delivered synchronously, within the same intervention and within the same task, personalised to the needs of the patient. Therefore, by combining three training methods that have shown effective outcomes on their own, we will explore the expected summative benefits of delivering a personalised intervention that integrates cognitive, somatosensory, and motor training. To enhance upper limb recovery after stroke, it is essential for rehabilitation interventions to drive processes of neuroplasticity and recovery of the nervous system 11 . Priming strategies to enhance neuroplasticity have been proposed as a restorative means of targeting neural mechanisms to reduce impairments in neurological conditions 12 . Current upper limb rehabilitation interventions have demonstrated limited benefits on functional outcomes 13 , which could result from insufficient dosage or inappropriate interventions 14 . This could be the result of a lack of understanding about the active ingredients that can optimise an intervention, the interactions between them, and their targets and mechanisms of action on enhancing upper limb recovery post-stroke 15 . Hence, it is unclear what constitutes optimal training strategies. The concept of intensive repetitive practice differs across cognitive, somatosensory, and motor training. Traditionally, motor training has prioritised a high volume of repetitions as a key active ingredient to induce cortical reorganisation 16 leading to improvements in motor learning 17 and motor function 18 . Although the optimal dose of therapy time and repetitions in stroke rehabilitation has yet to be determined, it is feasible for stroke survivors to complete at least 300 repetitions of task specific training of the upper limb in 1 hour 19 . Therefore, it is recommended that stroke survivors perform high numbers of repetitions while being sufficiently exposed to a target stimulus during therapy to improve their upper limb function. Alternatively, somatosensory retraining strategies have focused on duration of exposure to the stimuli to improve somatosensory function 20 . Similarly, cognitive training has focused on the overall duration of rehabilitation 21 . A randomized controlled trial (RCT) by Byl et al. found that at least 36 hours and 72 hours of combined somatosensory and motor training were required to improve functional independence and upper limb function after stroke 22 . The RCT by Chanubol found no significant improvement on upper limb function after 10 hours of cognitive sensory motor therapy 23 . The average intervention dose for cognitive training was 27.8 hours, even though it is acknowledged that the optimal timing, content, dose, and mode of delivering psychological interventions for post-stroke cognitive impairment is yet to be established 24 . Additionally, there is no data available on the optimal adherence rate to upper limb training needed to promote upper limb recovery post-stroke. AIMS AND OBJECTIVES This research proposal aims to investigate the feasibility of a personalised i ntegrated CO gnitive-somato S ensory- MO tor (iCOSMO) training intervention to improve upper limb recovery in people with chronic stroke. The objectives are: 1) to evaluate the feasibility, and 2) to determine the preliminary efficacy of a personalised integrated somatosensory-motor intervention in people with chronic stroke. HYPOTHESES We hypothesize that a personalised integrated cognitive-somatosensory-motor training intervention will be feasible amongst chronic stroke survivors. We also hypothesize that a personalised integrated cognitive-somatosensory-motor training approach will lead to greater improvement in somatosensory and motor recovery than a home-based motor exercise programme in people with chronic stroke. METHODS Study design We will conduct a prospective, two-arm pilot randomised controlled trial using a blinded assessor to evaluate the feasibility of the personalised iCOSMO training intervention to improve arm and hand function after stroke. This study will include three phases: baseline (4 weeks), intervention (6 weeks duration) and follow-up (4 weeks post-intervention). The study will be conducted over 2 years period. This study was approved by the University Health Network Research Ethics Board (22-5628). Reporting of this study will be guided by the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trails) statement 7 (Supplementary material 1). Study setting This study will be conducted at the Toronto Rehabilitation Institute, University Centre, University Health Network in Toronto (Canada). Participants Adults stroke survivors (>6 months post-stroke ) will be recruited for this study. To be included the individual must have sustained a first-time, clinically identified unilateral stroke with residual motor and/or somatosensory deficits in the upper limbs. Subjects will be excluded if they have: 1) a prior history of central nervous system dysfunction other than stroke, 2) upper limb deficits resulting from non-stroke pathology, and (3) inability to cooperate, follow instructions or provide consent. We aim to recruit 40 adult stroke survivors with stroke (>6 months) admitted in the out-patient rehabilitation program at the Toronto Rehabilitation Institute and West Park Healthcare Centre, Canada. This sample size is considered sufficient for this study to examine feasibility of the iCOSMO intervention as it is larger than prior feasibility studies 19, 25 . All participants will provide written informed consent, according to the Declaration of Helsinki. The functional status of participants will be determined by the Functional Independence Measure at discharge. The severity of motor impairment of the affected upper limb will be determined according to the Fugl-Meyer Assessment-Upper Extremity as follows: mild (0–27), moderate (28–41), and severe (42–60) 26 . The severity of somatosensory impairment of the affected arm will be defined according to the standardised deficit range score of the Tactile Discrimination Test (TDT) as follows: mild (0 to -33.33), moderate (-33.33 to -66.67) and severe (<-66.67) 27 . The severity of cognitive impairments will be classified according to the Montreal Cognitive Assessment as follows: scores of 11 or higher are classified as mild, and scores of less than 11 are classified as moderate/severe 28 . Procedure Consent, Screening and Randomization Potential participants will be sent the information sheet and consent form to review. If they express interest to learn further about this study, a virtual video-call will then be planned for potentially eligible patients by the therapist (UG) to inform them about the aims of the study and the procedures involved in participation. This study uses a two-step consenting process. Participants will be first asked to consent to being screened for eligibility by the therapist (UG) during an in-person visit. If eligible, a second consent is obtained for full study participation. After the baseline assessments, the participants will be randomly allocated to either the iCOSMO group or the home-GRASP group by another independent researcher. A computer-generated block randomization was performed in clusters of 2 participants to achieve a final 1:1 treatment to control allocation (iCOSMO and Home-GRASP, respectively). Intervention Critical components of the iCOSMO intervention The iCOSMO intervention will include 4 critical components: 1) a personalised training matrix of targeted cognitive-somatosensory-motor tasks to allow a systematic and progressive increase in the level of difficulty of the tasks (i.e. from easy to more difficult), 2) Varying levels of visual feedback (i.e. the tasks will be practised both with and without vision), 3) Targeted feedback on somatosensory-motor-cognitive task performance, and 4) intensive repetitive practice. iCOSMO Task design The iCOSMO intervention will primarily consist of two training approaches delivered consecutively to stroke survivors (Figure 3). The first training approach involves haptic exploratory tasks that focus on integrated somatosensory-motor variables during reaching and object manipulation to address movement, tactile and grasp deficits using a variety of objects (60 minutes) . The motor and sensory attributes of the movement and sensation tasks will be emphasized using a cognitive approach whereby the therapist guides the participant to identify and correct errors in performance using the Goal-Plan-Do-Check Strategy 29 . The motor tasks will vary the following characteristics: object width, object distance, multi-directional reaching in horizontal plane and reaching to different heights. These tasks will be combined with variations in somatosensory characteristics such as surface texture, surface friction and surface hardness. Additional tasks that integrate somatosensory-motor variables will involve shape discrimination, weight discrimination, small object recognition and object manipulation. The second training approach will focus on somatosensory-motor tasks including proprioceptive, motor and cognitive tasks using the Kinarm robotic exoskeleton (60 minutes). The Kinarm Exoskeleton (BKIN Technologies Ltd., Kingston, ON, Canada) (figure 4) is a robotic device that can comprehensively evaluate somatosensory, motor and cognitive function (Figure 4). The device is made up of two motorized Kinarm™ Exoskeleton robots for simultaneous bilateral assessments in the horizontal plane involving flexion and extension movements at the shoulder and elbow joints. The robotic device is also accompanied by a workstation with a two-dimensional non-immersive virtual reality system that displays each task in the horizontal plane. Ten tasks adapted from a robotic based intervention 30 will be delivered. These included the balance board, coin grab, duck hunt, goal scoring, guided reaching, ping pong, resisted reaching, shape tracing motor, shape tracing proprioception and hand ball tasks. These robotic tasks delivered goal-directed movements to different targets, high-precision bimanual movements, spatial motions of the limb around circles, spirals, ellipses (with and without visual feedback), rapid bimanual visuomotor skills, motor planning tasks with goal- directed feedback. Each of the tasks have varied levels of graded difficulty ranging from level 1 up to level 21. Personalised iCOSMO intervention training matrix The iCOSMO intervention training matrix will facilitate the delivery of the integrated cognitive-somatosensory-motor training tasks with a cognitive approach (Figure 5). The complete iCOSMO standardized training matrix is described in the Supplementary material 2. Personalised task as per specificity of deficits and level of difficulty The integrated cognitive-somatosensory-motor tasks are devised to maintain a systematic and progressive increase in the level of difficulty of the tasks in line with the Challenge Point Framework 31 . The Challenge Point Framework emphasizes the importance of maintaining an appropriate intensity to sufficiently challenge both somatosensory and motor functions for motor and somatosensory learning to occur. Prior to the start of the intervention, preliminary testing will be carried out on all participants to determine the specific deficits of all the cognitive, somatosensory, and motor submodalities. The participants will provide qualitative feedback on the difficulty of each task, ranked on a visual analogue scale (0-10). For example, if shape discrimination between a square and a triangular shape is too easy for a particular participant, this task will be removed for this individual and replaced by another shape discrimination task with a higher level of difficulty, such as discriminating between a square and a rectangle shape. If the participant has no/insignificant difficulty in shape discrimination, but significant deficits in tactile discrimination, the shape discrimination task can be removed entirely and replaced by additional tactile discrimination tasks (Figure 6). iCOSMO will be individualised to the specificity and severity of upper limb deficits, using a personalised standardised training matrix 32 . Dose of iCOSMO training Participants will receive a total of 36 hours of overall treatment duration (2 hours/session, 3 times/week, for 6 weeks). The first training approach using integrated somatosensory-motor variables during reaching, object manipulation and grasping will deliver 18 hours of therapy (60 minutes per session, 3 times per week, for 6 weeks). The second training approach using the Kinarm robotic will deliver 18 hours of exposure to cognitive-somatosensory-motor tasks (60 minutes per session, 3 times per week, for 6 weeks). It is anticipated that 8,100 repetitions of arm and hand movements (225 repetitions per session, 3 times per week, for 6 weeks) will be delivered in addition to the time of exposure to the Kinarm tasks. Rest periods of 15 minutes will be provided between the first and second training approaches. Home-Graded Repetitive Arm Supplementary Program The control group will receive a matched dose of a home-based motor (ony) exercise programme. The home-based motor exercise programme will be based on the Home Graded Repetitive Arm Supplementary Program focusing on stretching, arm strengthening, hand strengthening, coordination and hand Skills 33 . The Home Graded Repetitive Arm Supplementary Program (Home-GRASP) will be delivered 2 hours/session, 3 times/week, for 6 weeks. The participant can divide the exercises up into two 60-minute sessions or four 30-minute sessions if they wish. Every week, the participants will receive one session of one hour with a therapist virtually to guide the exercises and the other two sessions will be at the participant’s home. Safety We will monitor any adverse events that occur during the period of the study. Prior to each intervention or assessment session, we will ask participants whether they experienced any adverse events since the previous session. Events reported will be evaluated to determine if the cause is linked to the intervention provided in this study, which will then be reported as an adverse event. Outcome measures Feasibility measures The feasibility of operational aspects of the iCOSMO intervention trial will assess recruitment rates, the obstacles to recruitment and suitability of study procedures. These aspects are all in-line with both the recommendations of Orsmond and Cohn (2015) 34 for evaluating the feasibility of behavioural intervention studies and the Structured Assessment of Feasibility (SAFE) scale and checklist 35 . Table 1 summarizes the measures of the feasibility of the operational aspects of the iCOSMO intervention trial. Table 1. Measures of feasibility of the operational aspects of the iCOSMO intervention trial A. Evaluation of Recruitment Capability and Resulting Sample Characteristics 1. Recruitment rates 2. Obstacles to recruitment 3. Feasibility and suitability of eligibility criteria 4. Relevance of the intervention to the intended population B. Evaluation and Refinement of Data Collection Procedures and Outcome Measures 1. Feasibility and suitability of data collection procedures 2. Feasibility and suitability of amount of data collection 3. Consistency of outcome measures with the intended population 4. Adherence rates to data collection 5. Change on the most likely suitable outcome measures C. Evaluation of Acceptability and Suitability of Intervention and Study Procedures to participants 1. Retention and follow-up rates 2. Adherence rates to intervention attendance, and engagement D. Evaluation of Resources and Ability to Manage and Implement the Study and Intervention 1. Research capacity 2. Equipment sufficiency to conduct the study and intervention, including collection, management, and analysis of data 3. Ability to deal with broken, lost, or stolen equipment and materials 4. Software for capture and data processing Measures of fidelity will be recorded in each session using checklists to monitor intervention delivery 36 . These include: 1) the number of intervention sessions attended, 2) combinations of somatosensory-motor training variables practiced, 3) number of somatosensory-motor training combinations practiced, 4) amount of practice (number of repetitions), 5) scheduled training duration, i.e., time taken to complete the intervention session (including rest time), 6) actual training duration i.e., duration of active practice in one intervention session (number of minutes), and 7) adherence to the overall treatment (% of treatment sessions attended). The reason for nonattendance will be noted. Measures of fidelity and adherence will be taken during all sessions by the treating therapist. Evaluation of participant engagement will be based on self-reports of perceived difficulty and extent of engagement (adapted from Gerber et al. 37 ), and will be assessed at the end of the intervention period of the trial. The acceptability of the iCOSMO intervention will be evaluated through the participants’ perceptions of the contents of the iCOSMO intervention, efficacy of its delivery, and perceived impact, all using a patient feedback form 37, 38 . Perception of fatigue and pain will also be measured to monitor tolerability of the intervention sessions. The Stanford Fatigue Visual Analogue Scale (SFVAS), a single-item scale with a rating of 1 (no fatigue) to 10 (severe fatigue), will be used to assess the presence and extent of mental and physical fatigue 19 . The SFVAS and the PVAS will be measured before and immediately after each assessment and intervention session. Screening assessments Screening assessments will be conducted to determine the level of severity of impairments. These include the Functional Independence measure at discharge, Montreal Cognitive Assessment, the Rey Copy Figure Test, the Fugl-Meyer Assessment-Upper Extremity and the Tactile Discrimination Test. The severity of motor impairment of the affected upper limb will be determined according to the Fugl-Meyer Assessment-Upper Extremity as follows: mild (0–27), moderate (28–41), and severe (42–60) 26 . The severity of somatosensory impairment of the affected arm will be defined according to the standardised deficit range score of the Tactile Discrimination Test (TDT) as follows: mild (0 to -33.33), moderate (-33.33 to -66.67) and severe (<-66.67) 27 . The severity of cognitive impairments will be classified according to the Montreal Cognitive Assessment as follows: scores of 11 or higher are classified as mild, and scores of less than 11 are classified as moderate/severe 28 . We will conduct standardized robotic and clinical assessments to quantitatively evaluate upper limb somatosensory and motor impairments, performance and functions (Table 1) . Laboratory assessments Robotic assessments of cognitive-somatosensory-motor function will also be conducted using the Kinarm standard tasks™ (BKIN Technologies Ltd). The Dexterit-E data acquisition and experimental control software collects real-time data operated on a Windows™ based interface. During the experiment, the participants will be seated in a height-adjustable chair at the workstation of the Kinarm exoskeleton (BKIN Technologies Ltd., Kingston, ON, Canada). The participants’ will be provided anti-gravity support at proximal or distal arm segments. The participants’ head will be positioned in the centre of the visual field and the vision of their hands and arms will be occluded. A trained assessor will provide standardised instructions for each task prior to task performance by the participant. Data collection and analysis of the participants’ performances will be evaluated and quantified through an automated process using the Dexterit Version 3.10 software. Each task in the Kinarm standard tasks™ constitutes of approximately 9–20 performance metrics. For each performance metric, the data analysis software (Dexterit Version 3.10) will compute a Z-score that accounts for age, sex, and handedness. The Kinarm standard tasks™ will include: Cognitive tasks: (a) the Reverse Visually Guided Reaching, (b) the Trail Making A&B, (c) the Object Hit and Avoid 39 , (d) the Spatial Span Task 40 , (e) the Paired Associates Learning; Motor tasks: (f) the Visually Guided Reaching, (g) the Object Hit, (h) the Ball-on-Bar, (i) Arm Posture Perturbation, (j) Elbow Stretch Reflex; Somatosensory tasks: (k) Arm Positioning Matching and (l) the Arm Movement Matching 40 . Table 2 summarizes the description of the tasks. For uni-manual tasks on the Kinarm, participants will be tested on both the dominant and non-dominant arms. Table 2. Kinarm standard tasks Kinarm standard tasks Assessment type: measurement domain Description a) Reverse Visually Guided Reaching Performance: Cognition To assess attention, inhibitory control and cognitive control of visuomotor skills b) Trail Making A&B Performance: Cognition to assess task switching abilities c) Object Hit and Avoid Performance: Cognition to assess spatial attention, rapid motor selection and inhibition control d) Spatial Span Task Performance: Cognition To assess visuospatial working memory e) Paired Associates Learning Performance: Cognition To assess visuospatial working memory f) Visually Guided Reaching Performance: motor To assess visuomotor capabilities and multi-joint coordination g) Object Hit Performance: motor To assess visuomotor skills and spatial skills h) Ball-on-Bar Performance: motor To assess bimanual coordination and visuomotor skills i) Arm Posture Perturbation Performance: motor To assess the ability to respond to unexpected disturbances to the arm j) Elbow Stretch Reflex Performance: motor To quantify any change in muscle tone or muscle activity due to joint position or motion k) Arm Positioning Matching Performance: somatosensory To measure proprioceptive capabilities, specifically position sense in the upper limb l) Arm Movement Matching Performance: somatosensory To assess the ability to perceive limb motion in space Clinical assessments Clinical motor assessments will include the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) 26 which provides quantitative measures of sensory and motor impairments in the upper limbs. The FMA-UE is scored from 0-66 and has been recommended by the International Stroke Rehabilitation and Recovery Roundtable as a core measure 41 . The Action Research Arm Test (ARAT) assesses motor performance of the upper limb 42 . It consists of 19 tasks across the 4 subscales (grasp, grip, pinch, gross movement). The Wolf Motor Function Test (WMFT) evaluates the motor ability of the upper limbs during 15 timed function-based tasks and 2 strength-based tasks 43 . Maximum voluntary grip strength with the Jamar dynamometer will be used as a conventional measure of muscle strength in the upper limb post-stroke 44, 45 . Pulp-to-pulp pinch strength will be assessed using a pinch gauge (B & L Engineering) 46 . The Box and Block Test (BBT) will be used to assess gross manual dexterity 47, 48 . Clinical somatosensory assessments will include the Tactile discrimination test (TDT) which evaluates the ability to discriminate differences in finely graded texture surfaces 49, 50 . The Functional Tactile Object Recognition Test (FTORT) assesses the ability to match everyday objects which have selected sensory attributes such as crushability, texture, shape, weight, size, and temperature. It also assesses functional movements through the sense of touch 51 . The Wrist Position Sense Test (WPST) evaluated proprioception, quantifying the participant’s ability to determine wrist position after an imposed movement involving flexion-extension and ulnar-radial deviation 52 . Other assessments will include the evaluation of fatigue and pain. The Fatigue Assessment Scale (FAS) is a 10-item self-rated scale and will be used to evaluate physical and mental symptoms of chronic post-stroke fatigue 53 . The pain visual analogue scale (PVAS) is a single-item scale ranging from 0 (no pain) to 10 (excruciating pain) 54-56 . The assessments are summarized in Table 3. Table 3. Assessments Instrument Assessment type: measurement domain ICF domain Screening measures Functional Independence measure Clinician reported: disability Activity Montreal Cognitive Assessment Performance: Cognition Body functions and structures Rey Copy Figure Test Performance: Cognition Body functions and structures Fugl-Meyer Assessment-Upper Extremity Performance: Motor and somatosensory Body function and structure Tactile Discrimination Test Performance: somatosensory Body functions and structures Laboratory measures Kinarm standard tests Performance: somatosensory-motor Body functions and structures Clinical measures Fugl-Meyer Assessment-Upper Extremity (FMA-UE) 26 Performance: Motor and somatosensory Body function and structure Action Research Arm Test (ARAT) 42 Performance: motor Activity Wolf Motor Function Test (WMFT) 43 Performance: motor Activity Grip strength (Jamar dynamometer) 44, 45 Performance: motor Body functions and structures Box and Block Test (BBT) 47, 48 Observer: motor Activity Tactile Discrimination Test (TDT) 57 Performance: somatosensory Body functions and structures Wrist Position Sense Test (WPST) 52, 58 Performance: somatosensory Body functions and structures Functional Tactile Object Recognition Test (FTORT) 59 Performance: somatosensory Body functions and structures Fatigue Assessment Scale (FAS) 53 Participant reported: fatigue in daily life Activity and participation Stanford Fatigue Visual Analogue Scale (SFVAS) 60 Participant reported: mental and physical fatigue* Activity and participation Pain Visual Analogue Scale (PVAS) 61 Participant reported: pain* Activity and participation *Also measured pre and post treatment sessions and pre and post outcome assessment sessions SFVAS: fatigue(VAS4–10); no/minimal fatigue (VAS: 0–3) 62 ; FAS: fatigue ≥24 63 . Timing of outcome assessments The participants will be tested at the start and end of the baseline phase, at post-intervention and at 1-month follow-up. The outcome assessments will be conducted on two consecutive days (assessment session 1: laboratory assessments-1.5 hours, assessment session 2: clinical assessments-1.5 hours). Blinding The participants will be blinded to the hypotheses being tested in this study i.e the participant will not be informed about the feasibility testing of the iCOSMO training intervention. The participants will also not be informed which amongst the two interventions is the experimental or control interventions, respectively. This is important so as to control for the psychological effects associated with knowing group assignments. Participant blinding will reduce bias in this study with regards to their behaviour in this study, altered attitudes, compliance, cooperation, attendance and response to the outcome measures 64, 65 . Measurements will be performed by a blinded assessor therapist who has received training in use of assessments (different to the therapist delivering treatment). The assessor and statistician will be blinded to the hypotheses and group assignment. Unblinding of the assessor will not be allowed at any time point. Ethical considerations All data collected during this study will be confidential. All personal information will be removed from the data and will be replaced with a number. A list linking the number with participants’ names will be kept by the study team in a secure place, separate from the data file. Only key staff members will have access to the study data. Protocol modification In case of any important modification of the protocol including assessments or eligibility criteria, a formal amendment will be undertaken and approval will be required from the University Health Network Research Ethics Board before implementation. DATA ANALYSIS Feasibility Feasibility data will be reported using descriptive statistics. The iCOSMO intervention will be considered feasible if the measures of fidelity achieve at least 70% of the targeted amount of practice and adherence to overall treatment. Baseline Demographic variables will be analysed using standard descriptive methods, tested for normality using Shapiro-Wilks tests, and reported by treatment group. Categorical variables will be reported as frequency count (percentage), normally distributed continuous variables as mean (standard deviation) and ordinal and non-normally continuous variables as median (interquartile range). To identify any possible covariate imbalances between iCOSMO and GRASP groups, and possible randomization stratification levels in future full-scale trials, the variance ratios and empirical cumulative density functions (eCDFs) will be compared between treatment groups for key covariates. The stability of outcomes across the baseline phase was evaluated against two criteria: 1) absence of trend (almost flat) in raw scores across the two baseline timepoints when visually assessed; and 2) a variation of <5% was considered as an indication of stability during the baseline phase based upon recommendations for reproducibility studies 66, 67 . Stability across the baseline will indicate that the participant’s performance on outcome measures is not changing due to spontaneous recovery. Within and between group differences The mean (SD) or frequency count (percentage) for outcome measures will be reported by treatment group for each time point they are administered. Change scores will report the mean change (SD of the change) in the outcome variables by group between 1) Baseline and post-intervention, 2) between baseline and 4-weeks follow-up post-intervention, and 3) between post-intervention and 4-weeks follow-up post-intervention. Morris G will assess effect size of the mean changes for the 3 time-points and an effect size of 0.8 will be determined to be a large effect 68 . For continuous outcome measures between group analyses comparing scores at Time 1 (baseline) and Time 2 (post intervention), repeated measures ANCOVA will be performed if the data is normally distributed. For non-normally distributed data, the Friedman Test will be performed. A secondary analysis with 3 time points (at baseline, post-intervention and follow-up), a linear mixed effects method model will be performed with random effects. Since changes in performance in the outcome assessments across the group will include participants with varied nature of their deficits and levels of severity, it is also proposed that exploratory sub-analysis of changes in performance is conducted for participants with similar deficits and levels of severity. If possible, the characteristics of responders and non-responders will be investigated through uni- and multivariable regression analysis. As these are exploratory subgroup analyses, estimates and standard errors will be reported to provide indication of strength, direction and precision of the covariates effect on outcome measures and p-values will not be reported. Missing data will be assessed. As less than 5% of data will be assumed to be missing and Missing Completely at Random (MCAR), intention-to-treat principle will be applied to all analyses for any missing data. Analyses will be conducted using STATA version 18 for Windows, SAS 9.4 for Windows, and R version 4.2. A p-value < 0.05 will be used to indicate statistical significance for all analyses. To correct for multiplicity of testing, a false discovery rate correction will be applied and adjusted p-values will be reported. Improvements in Kinarm standard task performance will be considered clinically meaningful if there is a change from an impaired to a normal overall task score. By comparing to a normative dataset, participants who receive a task score of ≥ 1.96 are classified as having impaired upper extremity function, and those who receive a task score of < 1.96 are considered to have normative upper extremity function 69 . Improvements in clinical outcome measures will be considered meaningful if the changes reach or exceed the minimally clinically important difference. EXPECTED RESULTS It is expected that the ICOSMO intervention will be feasible and beneficial in delivering a personalised, progressive, high intensity repetition intervention combining cognitive, somatosensory and motor training in an integrated manner amongst stroke survivors. The iCOSMO study may also show that it is feasible to individualise the intervention tasks to the nature and severity of upper limb deficits. Participants are expected to achieve the target number of repetitions and time of exposure to tasks which has been evidenced to be feasible by Birkenmeier et al (2010) 19 . It is expected that participants will attend at least 75% of the intervention sessions 70 . It is possible for fatigue and pain to be higher at the end of the intervention session as compared to the beginning. However, the magnitude of the scores is expected to be relatively low. Consequently, we do not expect fatigue or pain to limit participation or adherence to the iCOSMO intervention. It is anticipated that the recruitment target of 40 participants will be achieved since this target is within the recruitment capability for each site we will be utilizing (30 participants per site per year). It is also expected that the iCOSMO training intervention will improve the arm and hand function of stroke survivors. We anticipate that participants will improve from baseline to post-intervention on all outcome measures evaluated in the iCOSMO trial. Additionally, improvements in performance scores on the robotic laboratory assessments, FMA-UE and the ARAT are anticipated to be similar to the minimally clinically important difference. We expect the gains in arm and hand function to be retained at the one-month follow-up. LIMITATIONS Several limitations need to be considered in this research proposal. This study has low statistical power, which will limit the external generalisability of the results. This will also limit the ability to conduct further statistical analyses to examine individual factors such as nature and severity of deficits within the sample. Future studies that have sufficient statistical power with larger sample sizes are required to further explore the efficacy of the iCOSMO intervention and its impact on upper limb deficits and severity. This study follows a stepwise and systematic approach for the development and evaluation of a complex intervention post-stroke, which emphasizes the importance of Phase 2 studies prior to a larger RCT 71 . In the future, a larger RCT comparing varied doses of iCOSMO required to maximize arm and hand recovery after stroke. We also do not know whether the target of 225 repetitions and time of exposure (per session) is optimal. Similarly, we do not know whether 36 hours or 18 sessions of iCOSMO intervention are ideal. The target of 70% fidelity and adherence is also arbitrary. This proposed work will lay down the groundwork needed before making comparisons with regards to dosage, intensity, and timing of training, first providing information on the potential benefits of higher doses, fidelity and adherence. The data from this study should be viewed as the start of an exploration of how personalised components of the intervention and dosage could be manipulated to optimise upper limb recovery. DISCUSSION This study will be the first to demonstrate whether it is both feasible and beneficial to deliver a personalised, progressive, high intensity repetition intervention integrating cognitive, somatosensory, and motor training in one protocol. Additionally, this proposed study will contribute to the literature on priming strategies as a restorative means of targeting neural mechanisms to reduce upper limb deficits post-stroke. It will help better understand the coupling action between cognitive, somatosensory, and motor training in task performance. Consequently, this project will directly advance knowledge in the field of upper extremity recovery following stroke. The systematic stepwise development of the iCOSMO intervention will inform about the design of the intervention with regards to the choice of active ingredients of the multiple components that can optimise the intervention, the complex interactions between them, their targets, and mechanisms of action so as to enhance upper limb recovery post-stroke. If the preliminary effects are beneficial, this study will contribute to better understanding of the mechanisms underlying cognitive, somatosensory, and motor learning-related neuroplasticity. If found to be both feasible and beneficial, this study will then also have laid down the groundwork needed before taking future steps towards a larger RCT of iCOSMO. This project also has the potential to help stroke survivors regain upper extremity faster than currently possible by cognitive, somatosensory, and motor training delivered separately. Improved arm and hand function will enhance participation and productivity for the estimated 400,000 stroke survivors in Canada and reduce burden on care providers. CONCLUSION The iCOSMO training intervention aims to simultaneously deliver cognitive, somatosensory, and motor rehabilitation to better restore arm and hand function in stroke survivors. If effective, the widespread implementation of the iCOSMO training intervention has the potential to increase arm and hand function in stroke survivors around the world, improving quality of life and the capacity to return to work, leisure, and family roles. Additionally, by improving treatment outcomes, the iCOSMO training intervention has the potential to lessen the global burden of stroke on the healthcare system, reducing inpatient stay times for survivors, in turn saving millions of dollars annually. Declarations Ethics approval and consent to participate: The study was approved by the University Health Network Research Ethics Board (22-5628). All participants will provide written informed consent, prior to participation in this study, according to the Declaration of Helsinki. Consent for publication: Not applicable Availability of data and materials: Not applicable Competing interests: The authors report there are no competing interests to declare. Funding: StrokeCog post-doctoral fellowship Authors' contributions: UG has led all stages of this study, including development of the intervention, development of the protocol and writing and reviewing the manuscript. LL has provided statistical guidance and reviewed the manuscript. MB has contributed to the development of the protocol and reviewed the manuscript. Acknowledgements: We would like to thank Dr Sean Dukelow from the University of Calgary, Koloman Varady and Anne Vivian-Scott from BKIN technologies Ltd for their contributions to the kinarm training tasks References Lang CE, Bland MD, Bailey RR, Schaefer SY, Birkenmeier RL. Assessment of upper extremity impairment, function, and activity after stroke: foundations for clinical decision making. J Hand Ther. 2013;26(2):104-14;quiz 15. Kwakkel G, Kollen BJ, van der Grond J, Prevo AJ. Probability of regaining dexterity in the flaccid upper limb: Impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34(9):2181-6. Carey L, Matyas T. Frequency of discriminative sensory loss in the hand after stroke. Journal of rehabilitation medicine : official journal of the UEMS European Board of Physical and Rehabilitation Medicine. 2011;43:257-63. Lo JW, Crawford JD, Desmond DW, Godefroy O, Jokinen H, Mahinrad S, et al. 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J Rehabil Med. 2010;42(4):310-4. Bourke TC, Lowrey CR, Dukelow SP, Bagg SD, Norman KE, Scott SH. A robot-based behavioural task to quantify impairments in rapid motor decisions and actions after stroke. J Neuroeng Rehabil. 2016;13(1):91. BKIN Technologies Ltd. Kinarm Standard Test, Kingston, ON, Canada [Available from: https://kinarm.com/solutions/kinarm-standard-tests/. Kwakkel G, Lannin N, Borschmann K, English C, Ali M, Churilov L, et al. Standardized Measurement of Sensorimotor Recovery in Stroke Trials: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable. Neurorehabilitation and Neural Repair. 2017;31:784-92. Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment and research. Int J Rehabil Res. 1981;4(4):483-92. Wolf SL, Catlin PA, Ellis M, Archer AL, Morgan B, Piacentino A. Assessing Wolf motor function test as outcome measure for research in patients after stroke. Stroke. 2001;32(7):1635-9. Bohannon R. Adequacy of hand-grip dynamometry for characterizing upper limb strength after stroke. Isokinetic Exercise Science. 2004;12:263-5. Ekstrand E, Lexell J, Brogardh C. Grip strength is a representative measure of muscle weakness in the upper extremity after stroke. Topics in stroke rehabilitation. 2016;23(6):400-5. Aguiar LT, Martins JC, Lara EM, Albuquerque JA, Teixeira-Salmela LF, Faria CDCM. Dynamometry for the measurement of grip, pinch, and trunk muscles strength in subjects with subacute stroke: Reliability and different number of trials. Brazilian Journal of Physical Therapy. 2016;20(5):395-404. Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. The American journal of occupational therapy : official publication of the American Occupational Therapy Association. 1985;39(6):386-91. Oliveira CS, Almeida CS, Freias LC, Santana R, Fernandes G, Junior PRF, et al. Use of the Box and Block Test for the evaluation of manual dexterity in individuals with central nervous system disorders: A systematic review. Manual Therapy Posturology Rehabilation Journal. 2016;14. Carey LM. Somatosensory Loss after Stroke. 1995;7(1):51-91. Carey L. Tactile and proprioceptive discrimination loss after stroke: Training effects and quantitative measurement. Melbourne: LaTrobe University; 1993. Carey L, Nankervis J, LeBlanc S, Harvey L, editors. A new functional tactual object recognition test (fTORT) for stroke clients: Normative standards and discriminative validity. 14th International Congress of the World Federation of Occupational Therapists; 2006; Sydney, Australia. Carey LM, Oke LE, Matyas TA. Impaired limb position sense after stroke: a quantitative test for clinical use. Arch Phys Med Rehabil. 1996;77(12):1271-8. Mead G, Lynch J, Greig C, Young A, Lewis S, Sharpe M. Evaluation of fatigue scales in stroke patients. Stroke. 2007;38(7):2090-5. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 2011;63(S11):S240-S52. Ritter PL, González VM, Laurent DD, Lorig KR. Measurement of pain using the visual numeric scale. J Rheumatol. 2006;33(3):574-80. Williamson A, Hoggart B. Pain: A review of three commonly used pain rating scales. J Clin Nurs. 2005;14(7):798-804. Carey LM, Oke LE, Matyas TA. Impaired touch discrimination after stroke: A quantiative test. Neurorehabilitation and Neural Repair. 1997;11(4):219-32. Carey L. Tactile and proprioceptive discrimination loss after stroke: Training effects and quantitative measurement. Melbourne, VICTORIA: LaTrobe University; 1993. Carey L, Nankervis J, LeBlanc S, Harvey L, editors. A new functional tactual object recognition test (fTORT) for stroke clients: Normative standards and discriminative validity. 14th International Congress of the World Federation of Occupational Therapists; 2006; Sydney, Australia. Stanford P, Education, Center R. Fatigue Visual Numeric Scale. 2015. Price CI, Curless RH, Rodgers H. Can stroke patients use visual analogue scales? Stroke. 1999;30(7):1357-61. Logan A, Freeman J, Kent B, Pooler J, Creanor S, Vickery J, et al. Standing Practice In Rehabilitation Early After Stroke (SPIRES): A functional standing frame programme (prolonged standing and repeated sit to stand) to improve function and quality of life and reduce neuromuscular impairment in people with severe sub-acute stroke—A protocol for a feasibility randomised controlled trial. Pilot and Feasibility Studies. 2018;4(1):66. Cumming TB, Mead G. Classifying post-stroke fatigue: Optimal cut-off on the Fatigue Assessment Scale. J Psychosom Res. 2017;103:147-9. J. PS. Clinical trials: A practical approach. Chichester, England: Wiley; 1983. Karanicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: blinding: who, what, when, why, how? Can J Surg. 2010;53(5):345-8. Hopkins WG. Measures of reliability in sports medicine and science. Sports medicine (Auckland, NZ). 2000;30(1):1-15. Hopkins WG. A new view of statistics: Internet Society for Sport Science; 2000 [Available from: http://www.sportsci.org/resource/stats/. Morris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organizational Research Methods. 2008;11(2):364-86. Simmatis LER, Early S, Moore KD, Appaqaq S, Scott SH. Statistical measures of motor, sensory and cognitive performance across repeated robot-based testing. Journal of NeuroEngineering and Rehabilitation. 2020;17(1):86. Scianni A, Teixeira-Salmela LF, Ada L. Challenges in recruitment, attendance and adherence of acute stroke survivors to a randomized trial in Brazil: a feasibility study. Brazilian Journal of Physical Therapy. 2012;16:40-5. Bernhardt J, Hayward KS, Dancause N, Lannin NA, Ward NS, Nudo RJ, et al. A Stroke Recovery Trial Development Framework: Consensus-Based Core Recommendations from the Second Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2019;33(11):959-69. Supplementary Files iCOSMOSupplementarymaterial.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 14 Jul, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 17 Mar, 2025 Editor assigned by journal 13 Mar, 2025 First submitted to journal 11 Mar, 2025 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. 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B1 Ax: Baseline 1 assessment, B2 Ax: Baseline 2 assessment, Post-Int Ax: Post-intervention assessment, FU Ax: Follow-up assessment T1\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/32adf3745c0819563e668b18.png"},{"id":79243307,"identity":"83f23aa7-0238-4ec6-9e57-717d59f323fe","added_by":"auto","created_at":"2025-03-26 06:24:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":22946,"visible":true,"origin":"","legend":"\u003cp\u003eiCOSMO Model\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/27d338514c37e41f3466d2e1.png"},{"id":79243302,"identity":"66c1b31e-030f-4521-b26f-f2a1646e95db","added_by":"auto","created_at":"2025-03-26 06:24:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":78705,"visible":true,"origin":"","legend":"\u003cp\u003eKinarm exoskeleton\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/0e0d51eb6095da1f0a1b10ab.png"},{"id":79243303,"identity":"989e4911-110a-4a7c-8320-45389d0b2e5e","added_by":"auto","created_at":"2025-03-26 06:24:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":37131,"visible":true,"origin":"","legend":"\u003cp\u003eConditions of practice and number of repetitions with or without vision: \u003cem\u003eSomatosensory-motor combination feedback task: Distance and Texture - Short distance parameter and Shape\u003c/em\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/8593eeab8a26ef97cfcfe9ce.png"},{"id":79243693,"identity":"ebabcc8e-ff4d-4ec7-bb93-2dd4c3b5aa16","added_by":"auto","created_at":"2025-03-26 06:32:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":23190,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePersonalised task as per specificity of deficits and level of difficulty\u003c/em\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/007d2d1fbcb234816f224ad4.png"},{"id":79244652,"identity":"75c29bc6-f089-4d61-ab6b-f29a81bd6de5","added_by":"auto","created_at":"2025-03-26 06:48:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1259750,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/97487fd9-9fb4-4186-9b59-b27cc3c8c04d.pdf"},{"id":79243310,"identity":"7c73de5e-bf41-4e2f-ace8-87b11674aec3","added_by":"auto","created_at":"2025-03-26 06:24:03","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":118834,"visible":true,"origin":"","legend":"","description":"","filename":"iCOSMOSupplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6206942/v1/ac074aa3416a656edf02185c.docx"}],"financialInterests":"","formattedTitle":"An integrated COgnitive-somatoSensory-MOtor training intervention for upper limb recovery after stroke: Protocol for a Phase II randomized controlled trial","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eStroke is one of the leading causes of disability in Canada and around the world. Upper limb impairments after stroke are the primary cause of functional limitations\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. More than 85% of stroke survivors suffer from residual upper limb movement deficits due to incomplete motor recovery\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, and one in two stroke survivors have deficits in somato (body) sensations\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Similarly, up to 44% of stroke survivors experience cognitive impairments\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBoth somatosensory and motor function are essential in the performance of daily activities using the upper limbs. Motor, somatosensory, and cognitive function are all integrated and tightly coupled in action in everyday life\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. It is hypothesized that improvement in cognitive function could enhance both somatosensory and motor function after stroke. Previous work has shown benefits associated with observation training prior to completing a motor task after stroke, indicating there is a link with cognitive training and motor performance\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. So far, cognitive training has rarely been combined with either somatosensory or motor training in stroke rehabilitation. Only one study by Chanubol et al. investigated the effects of cognitive sensory motor training therapy using the Perfetti method. This focused on retraining of sensory guided motor control, with particular emphasis on joint position perception\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Cognitive training using the Kinarm robotic exoskeleton (Kinarm, Kingston, Ontario) can also help improve cognitive-sensory function\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, which in turn has impacts on somatosensory and motor function. So far, there has been no intervention to combine somatosensory, motor, and cognitive training in an integrated manner within the same protocol to improve upper limb function after stroke. Hence, there is a critical need for the development of new, more effective treatments.\u003c/p\u003e \u003cp\u003eThe theoretical underpinning behind this intervention is the work completed by Filmer, Mattingley, Marois, and Dux in 2013. By disrupting prefrontal cortex activity using transcranial direct current stimulation, performance gains in a somatosensory-motor task were prevented\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Our group inferred that if disruptions to cognitive function impair sensory-motor function, then improvements in cognitive function through training would likely heighten somatosensory-motor performance. Additionally, tailoring of the active ingredients and dosage parameters of an intervention towards the participants\u0026rsquo; characteristics with regards to the nature and severity of deficits is critical. This reinforces a personalised training approach according to the needs of the participant, which is recommended in rehabilitation trials post-stroke\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. The proposed novel intervention combines cognitive, somatosensory, and motor training in an integrated manner which is delivered synchronously, within the same intervention and within the same task, personalised to the needs of the patient. Therefore, by combining three training methods that have shown effective outcomes on their own, we will explore the expected summative benefits of delivering a personalised intervention that integrates cognitive, somatosensory, and motor training.\u003c/p\u003e \u003cp\u003eTo enhance upper limb recovery after stroke, it is essential for rehabilitation interventions to drive processes of neuroplasticity and recovery of the nervous system\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Priming strategies to enhance neuroplasticity have been proposed as a restorative means of targeting neural mechanisms to reduce impairments in neurological conditions\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Current upper limb rehabilitation interventions have demonstrated limited benefits on functional outcomes\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e, which could result from insufficient dosage or inappropriate interventions\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. This could be the result of a lack of understanding about the active ingredients that can optimise an intervention, the interactions between them, and their targets and mechanisms of action on enhancing upper limb recovery post-stroke\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Hence, it is unclear what constitutes optimal training strategies.\u003c/p\u003e \u003cp\u003eThe concept of intensive repetitive practice differs across cognitive, somatosensory, and motor training. Traditionally, motor training has prioritised a high volume of repetitions as a key active ingredient to induce cortical reorganisation\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e leading to improvements in motor learning\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e and motor function\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Although the optimal dose of therapy time and repetitions in stroke rehabilitation has yet to be determined, it is feasible for stroke survivors to complete at least 300 repetitions of task specific training of the upper limb in 1 hour\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Therefore, it is recommended that stroke survivors perform high numbers of repetitions while being sufficiently exposed to a target stimulus during therapy to improve their upper limb function. Alternatively, somatosensory retraining strategies have focused on duration of exposure to the stimuli to improve somatosensory function\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Similarly, cognitive training has focused on the overall duration of rehabilitation\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. A randomized controlled trial (RCT) by Byl et al. found that at least 36 hours and 72 hours of combined somatosensory and motor training were required to improve functional independence and upper limb function after stroke\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. The RCT by Chanubol found no significant improvement on upper limb function after 10 hours of cognitive sensory motor therapy\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. The average intervention dose for cognitive training was 27.8 hours, even though it is acknowledged that the optimal timing, content, dose, and mode of delivering psychological interventions for post-stroke cognitive impairment is yet to be established\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Additionally, there is no data available on the optimal adherence rate to upper limb training needed to promote upper limb recovery post-stroke.\u003c/p\u003e\n\u003ch3\u003eAIMS AND OBJECTIVES\u003c/h3\u003e\n\u003cp\u003eThis research proposal aims to investigate the feasibility of a personalised \u003cb\u003ei\u003c/b\u003entegrated \u003cb\u003eCO\u003c/b\u003egnitive-somato\u003cb\u003eS\u003c/b\u003eensory-\u003cb\u003eMO\u003c/b\u003etor \u003cb\u003e(iCOSMO)\u003c/b\u003e training intervention to improve upper limb recovery in people with chronic stroke. The objectives are: 1) to evaluate the feasibility, and 2) to determine the preliminary efficacy of a personalised integrated somatosensory-motor intervention in people with chronic stroke.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eHYPOTHESES\u003c/h2\u003e \u003cp\u003eWe hypothesize that a personalised integrated cognitive-somatosensory-motor training intervention will be feasible amongst chronic stroke survivors. We also hypothesize that a personalised integrated cognitive-somatosensory-motor training approach will lead to greater improvement in somatosensory and motor recovery than a home-based motor exercise programme in people with chronic stroke.\u003c/p\u003e \u003c/div\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cu\u003eStudy design\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWe will conduct a prospective, two-arm pilot randomised controlled trial using a blinded assessor\u0026nbsp;to evaluate the feasibility of the personalised iCOSMO training intervention to improve arm and hand function after stroke. \u0026nbsp;This study will include three phases: baseline (4 weeks), intervention (6 weeks duration) and follow-up (4 weeks post-intervention). The study will be conducted over 2 years period. This study was approved by the University Health Network Research Ethics Board (22-5628).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eReporting of this study will be guided by the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trails) statement\u003csup\u003e7\u003c/sup\u003e (Supplementary material 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eStudy setting\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study will be conducted at the Toronto Rehabilitation Institute, University Centre, University Health Network in Toronto (Canada).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eParticipants\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAdults stroke survivors (\u0026gt;6 months post-stroke ) will be recruited for this study.\u0026nbsp;To be included the individual must have sustained a first-time, clinically identified unilateral stroke with residual motor and/or somatosensory deficits in the upper limbs. Subjects will be excluded if they have: 1) a prior history of central nervous system dysfunction other than stroke, 2) upper limb deficits resulting from non-stroke pathology, and (3) inability to cooperate, follow instructions or provide consent. We aim to recruit 40\u0026nbsp;adult stroke survivors with stroke (\u0026gt;6 months) admitted in the out-patient rehabilitation program at the Toronto Rehabilitation Institute and West Park Healthcare Centre, Canada. This sample size is considered sufficient for this study to examine feasibility of the iCOSMO intervention as it is larger than prior feasibility studies\u003csup\u003e19, 25\u003c/sup\u003e.\u0026nbsp;All participants will provide written informed consent, according to the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eThe functional status of participants will be determined by the Functional Independence Measure at discharge. The severity of motor impairment of the affected upper limb will be determined according to the Fugl-Meyer Assessment-Upper Extremity as follows:\u0026nbsp;mild (0\u0026ndash;27), moderate (28\u0026ndash;41), and severe (42\u0026ndash;60)\u003csup\u003e26\u003c/sup\u003e.\u0026nbsp;The severity of somatosensory impairment of the affected arm will be defined according to the standardised deficit range score of the Tactile Discrimination Test (TDT) as follows: mild (0 to -33.33), moderate (-33.33 to -66.67) and severe (\u0026lt;-66.67)\u003csup\u003e27\u003c/sup\u003e. The severity of cognitive impairments will be classified according to the Montreal Cognitive Assessment as follows: scores of 11 or higher are classified as mild, and scores of less than 11 are classified as moderate/severe\u003csup\u003e28\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eProcedure\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent, Screening and Randomization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePotential participants will be sent the information sheet and consent form to review. If they express interest to learn further about this study, a virtual video-call will then be planned for potentially eligible patients by the therapist (UG) to inform them about the aims of the study and the procedures involved in participation. This study uses a two-step consenting process. Participants will be first asked to consent to being screened for eligibility by the therapist (UG) during an in-person visit. If eligible, a second consent is obtained for full study participation. After the baseline assessments, the participants will be randomly allocated to either the iCOSMO group or the home-GRASP group by another independent researcher. A computer-generated block randomization was performed in clusters of 2 participants to achieve a final 1:1 treatment to control allocation\u003c/p\u003e\n\u003cp\u003e(iCOSMO and Home-GRASP, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eIntervention\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCritical components of the iCOSMO intervention\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe iCOSMO intervention will include 4 critical components: 1) a personalised training matrix of targeted cognitive-somatosensory-motor tasks to allow a systematic and progressive increase in the level of difficulty of the tasks (i.e. from easy to more difficult), 2) Varying levels of visual feedback (i.e. the tasks will be practised both with and without vision), 3) Targeted feedback on somatosensory-motor-cognitive task performance, and 4) intensive repetitive practice.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eiCOSMO Task design\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe iCOSMO intervention will primarily consist of two training approaches delivered consecutively to stroke survivors (Figure 3). The \u003cstrong\u003efirst\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;training approach\u003c/strong\u003e involves haptic exploratory tasks that focus on integrated somatosensory-motor variables during reaching and object manipulation to address movement, tactile and grasp deficits using a variety of objects\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e(60 minutes)\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe motor and sensory attributes of the movement and sensation tasks will be emphasized using a \u0026nbsp;cognitive approach whereby the therapist guides the participant to identify and correct errors in performance using the Goal-Plan-Do-Check Strategy\u003csup\u003e29\u003c/sup\u003e. The motor tasks will vary the following characteristics: object width, object distance, multi-directional reaching in horizontal plane and reaching to different heights. These tasks will be combined with variations in somatosensory characteristics such as surface texture, surface friction and surface hardness. Additional tasks that integrate somatosensory-motor variables will involve shape discrimination, weight discrimination, small object recognition and object manipulation.\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003esecond\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;training approach\u003c/strong\u003e will focus on somatosensory-motor tasks including proprioceptive, motor and cognitive tasks \u003cstrong\u003eusing the Kinarm\u003c/strong\u003e robotic exoskeleton (60 minutes). The Kinarm Exoskeleton (BKIN Technologies Ltd., Kingston, ON, Canada) (figure 4) is a robotic device that can comprehensively evaluate somatosensory, motor and cognitive function (Figure 4). The device is made up of two motorized Kinarm\u0026trade; Exoskeleton robots for simultaneous bilateral assessments in the horizontal plane involving flexion and extension movements at the shoulder and elbow joints. The robotic device is also accompanied by a workstation with a two-dimensional non-immersive virtual reality system that displays each task in the horizontal plane.\u003c/p\u003e\n\u003cp\u003eTen tasks adapted from a robotic based intervention\u003csup\u003e30\u003c/sup\u003e will be delivered. These included the balance board, coin grab, duck hunt, goal scoring, guided reaching, ping pong, resisted reaching, shape tracing motor, shape tracing proprioception and hand ball tasks. \u0026nbsp;These robotic tasks delivered goal-directed movements to different targets, high-precision bimanual movements, spatial motions of the limb around circles, spirals, ellipses (with and without visual feedback), rapid bimanual visuomotor skills, motor planning tasks with goal- directed feedback. Each of the tasks have varied levels of graded difficulty ranging from level 1 up to level 21.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePersonalised iCOSMO intervention training matrix\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003eiCOSMO\u003c/strong\u003e intervention training matrix will facilitate the delivery of the integrated cognitive-somatosensory-motor training tasks with a cognitive approach (Figure 5). The complete iCOSMO standardized training matrix is described in the Supplementary material 2.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePersonalised task as per specificity of deficits and level of difficulty\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe integrated cognitive-somatosensory-motor tasks are devised to maintain a systematic and progressive increase in the level of difficulty of the tasks in line with the Challenge Point Framework\u003csup\u003e31\u003c/sup\u003e. The Challenge Point Framework emphasizes the importance of maintaining an appropriate intensity to sufficiently challenge both somatosensory and motor functions for motor and somatosensory learning to occur.\u0026nbsp;Prior to the start of the intervention, preliminary testing will be carried out on all participants to determine the specific deficits of all the cognitive, somatosensory, and motor submodalities. The participants will provide qualitative feedback on the difficulty of each task, ranked on a visual analogue scale (0-10). For example, if shape discrimination between a square and a triangular shape is too easy for a particular participant, this task will be removed for this individual and replaced by another shape discrimination task with a higher level of difficulty, such as discriminating between a square and a rectangle shape. If the participant has no/insignificant difficulty in shape discrimination, but significant deficits in tactile discrimination, the shape discrimination task can be removed entirely and replaced by additional tactile discrimination tasks (Figure 6).\u0026nbsp;iCOSMO will be individualised to the specificity and severity of upper limb deficits, using a personalised standardised training matrix\u003csup\u003e32\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDose of iCOSMO training\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will receive a total of 36 hours of overall treatment duration (2 hours/session, 3 times/week, for 6 weeks). The first training approach using integrated somatosensory-motor variables during reaching, object manipulation and grasping will deliver 18 hours of therapy (60 minutes per session, 3 times per week, for 6 weeks). The second training approach using the Kinarm robotic will deliver 18 hours of exposure to cognitive-somatosensory-motor tasks (60 minutes per session, 3 times per week, for 6 weeks). It is anticipated that 8,100 repetitions of arm and hand movements (225 repetitions per session, 3 times per week, for 6 weeks) will be delivered in addition to the time of exposure to the Kinarm tasks.\u003c/p\u003e\n\u003cp\u003eRest periods of 15 minutes will be provided between the first and second training approaches.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHome-Graded Repetitive Arm Supplementary Program\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe control group will receive a matched dose of a home-based motor (ony) exercise programme. The home-based motor exercise programme will be based on the Home Graded Repetitive Arm Supplementary Program focusing on stretching, arm strengthening, hand strengthening, coordination and hand Skills\u003csup\u003e33\u003c/sup\u003e. The Home Graded Repetitive Arm Supplementary Program (Home-GRASP) will be delivered 2 hours/session, 3 times/week, for 6 weeks. The participant can divide the exercises up into two 60-minute sessions or four 30-minute sessions if they wish. Every week, the participants will receive one session of one hour with a therapist virtually to guide the exercises and the other two sessions will be at the participant\u0026rsquo;s home.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSafety\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe will monitor any adverse events that occur during the period of the study. Prior to each intervention or assessment session, we will ask participants whether they experienced any adverse events since the previous session. Events reported will be evaluated to determine if the cause is linked to the intervention provided in this study, which will then be reported as an adverse event.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eOutcome measures\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFeasibility measures\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe feasibility of operational aspects of the iCOSMO intervention trial will assess recruitment rates, the obstacles to recruitment and suitability of study procedures. These aspects are all in-line with both the recommendations of Orsmond and Cohn (2015)\u003csup\u003e34\u003c/sup\u003e for evaluating the feasibility of behavioural intervention studies and the Structured Assessment of Feasibility (SAFE) scale and checklist\u003csup\u003e35\u003c/sup\u003e. Table 1 summarizes the measures of the feasibility of the operational aspects of the iCOSMO intervention trial.\u003c/p\u003e\n\u003cp\u003eTable 1. Measures of feasibility of the operational aspects of the iCOSMO intervention trial\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA. \u0026nbsp; \u0026nbsp; Evaluation of Recruitment Capability and Resulting Sample Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1. Recruitment rates \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. Obstacles to recruitment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e3. Feasibility and suitability of eligibility criteria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e4. Relevance of the intervention to the intended population\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Evaluation and Refinement of Data Collection Procedures and Outcome Measures\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1. Feasibility and suitability of data collection procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. Feasibility and suitability of amount of data collection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e3. Consistency of outcome measures with the intended population\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e4. Adherence rates to data collection\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e5. Change on the most likely suitable outcome measures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC. Evaluation of Acceptability and Suitability of Intervention and Study Procedures to participants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1. Retention and follow-up rates\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. Adherence rates to intervention attendance, and engagement\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD. Evaluation of Resources and Ability to Manage and Implement the Study and Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e1. Research capacity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e2. Equipment sufficiency to conduct the study and intervention, including collection, management, and analysis of data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e3. Ability to deal with broken, lost, or stolen equipment and materials\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e4. Software for capture and data processing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMeasures of fidelity\u0026nbsp;will be recorded in each session using checklists to monitor intervention delivery\u003csup\u003e36\u003c/sup\u003e. These include: 1) the number of intervention sessions attended, 2) combinations of somatosensory-motor training variables practiced, 3) number of somatosensory-motor training combinations practiced, 4) amount of practice (number of repetitions), 5) scheduled training duration, i.e., time taken to complete the intervention session (including rest time), 6) actual training duration i.e., duration of active practice in one intervention session (number of minutes), and 7) adherence to the overall treatment (% of treatment sessions attended). The reason for nonattendance will be noted.\u003c/p\u003e\n\u003cp\u003eMeasures of fidelity and adherence will be taken during all sessions by the treating therapist. Evaluation of participant engagement will be based on self-reports of perceived difficulty and extent of engagement (adapted from Gerber et al.\u003csup\u003e37\u003c/sup\u003e), and will be assessed at the end of the intervention period of the trial. The acceptability of the iCOSMO intervention\u0026nbsp;will be evaluated through the participants\u0026rsquo; perceptions of the contents of the iCOSMO intervention, efficacy of its delivery, and perceived impact, all using a patient feedback form\u003csup\u003e37, 38\u003c/sup\u003e.\u0026nbsp;Perception of fatigue and pain will also be measured to monitor tolerability of the intervention sessions. The Stanford Fatigue Visual Analogue Scale (SFVAS), a single-item scale with a rating of 1 (no fatigue) to 10 (severe fatigue), will be used to assess the presence and extent of mental and physical fatigue\u003csup\u003e19\u003c/sup\u003e. The SFVAS and the PVAS will be measured before and immediately after each assessment and intervention session.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eScreening assessments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eScreening assessments will be conducted to determine the level of severity of impairments. These include the Functional Independence measure at discharge, Montreal Cognitive Assessment, the\u0026nbsp;Rey Copy Figure Test, the Fugl-Meyer Assessment-Upper Extremity and the Tactile Discrimination Test. The severity of motor impairment of the affected upper limb will be determined according to the Fugl-Meyer Assessment-Upper Extremity as follows:\u0026nbsp;mild (0\u0026ndash;27), moderate (28\u0026ndash;41), and severe (42\u0026ndash;60)\u003csup\u003e26\u003c/sup\u003e.\u0026nbsp;The severity of somatosensory impairment of the affected arm will be defined according to the standardised deficit range score of the Tactile Discrimination Test (TDT) as follows: mild (0 to -33.33), moderate (-33.33 to -66.67) and severe (\u0026lt;-66.67)\u003csup\u003e27\u003c/sup\u003e. The severity of cognitive impairments will be classified according to the Montreal Cognitive Assessment as follows: scores of 11 or higher are classified as mild, and scores of less than 11 are classified as moderate/severe\u003csup\u003e28\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWe will conduct standardized robotic and clinical assessments to quantitatively evaluate upper limb somatosensory and motor impairments, performance and functions (Table 1)\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLaboratory assessments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eRobotic assessments of cognitive-somatosensory-motor function will also be conducted using the Kinarm standard tasks\u0026trade; (BKIN Technologies Ltd). The Dexterit-E data acquisition and experimental control software collects real-time data operated on a Windows\u0026trade; based interface.\u003c/p\u003e\n\u003cp\u003eDuring the experiment, the participants will be seated\u0026nbsp;in a height-adjustable chair at the workstation of the Kinarm exoskeleton (BKIN Technologies Ltd., Kingston, ON, Canada). The participants\u0026rsquo; will be provided anti-gravity support at proximal or distal arm segments. The participants\u0026rsquo; head will be positioned in the centre of the visual field\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eand the vision of their hands and arms will be occluded. A trained assessor will provide standardised instructions for each task prior to task performance by the participant. Data collection and analysis of the participants\u0026rsquo; performances will be evaluated and quantified through an automated process using the Dexterit Version 3.10 software. Each task in the Kinarm standard tasks\u0026trade; constitutes of approximately 9\u0026ndash;20 performance metrics. For each performance metric, the data analysis software (Dexterit Version 3.10) will compute a Z-score that accounts for age, sex, and handedness.\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;Kinarm standard tasks\u0026trade; will include: Cognitive tasks: (a) the Reverse Visually Guided Reaching, (b) the Trail Making A\u0026amp;B, (c) the Object Hit and Avoid\u003csup\u003e39\u003c/sup\u003e, (d) the Spatial Span Task\u003csup\u003e40\u003c/sup\u003e, (e) the Paired Associates Learning; Motor tasks: (f) the Visually Guided Reaching, (g) the Object Hit, (h) the Ball-on-Bar, (i) Arm Posture Perturbation, (j) Elbow Stretch Reflex; Somatosensory tasks: (k) Arm Positioning Matching and (l) the Arm Movement Matching\u003csup\u003e40\u003c/sup\u003e. Table 2 summarizes the description of the tasks.\u003c/p\u003e\n\u003cp\u003eFor uni-manual tasks on the Kinarm, participants will be tested on both the dominant and non-dominant arms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Kinarm standard tasks\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKinarm standard tasks\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAssessment type: measurement domain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescription\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ea) \u0026nbsp; \u0026nbsp; \u0026nbsp;Reverse Visually Guided Reaching\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess attention, inhibitory control and cognitive control of visuomotor skills\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003eb) \u0026nbsp; \u0026nbsp; \u0026nbsp;Trail Making A\u0026amp;B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eto assess task switching abilities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ec) \u0026nbsp; \u0026nbsp; \u0026nbsp; Object Hit and Avoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eto assess spatial attention, rapid motor selection and inhibition control\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ed) \u0026nbsp; \u0026nbsp; \u0026nbsp;Spatial Span Task\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess visuospatial working memory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ee) \u0026nbsp; \u0026nbsp; \u0026nbsp;Paired Associates Learning\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess visuospatial working memory\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ef) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Visually Guided Reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess visuomotor capabilities and multi-joint coordination\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003eg) \u0026nbsp; \u0026nbsp; \u0026nbsp;Object Hit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess visuomotor skills and spatial skills\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003eh) \u0026nbsp; \u0026nbsp; \u0026nbsp;Ball-on-Bar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess bimanual coordination and visuomotor skills\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ei) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Arm Posture Perturbation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess the ability to respond to unexpected disturbances to the arm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ej) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Elbow Stretch Reflex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo quantify any change in muscle tone or muscle activity due to joint position or motion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003ek) \u0026nbsp; \u0026nbsp; \u0026nbsp; Arm Positioning Matching\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo measure proprioceptive capabilities, specifically position sense in the upper limb\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 28.972%;\"\u003e\n \u003cp\u003el) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Arm Movement Matching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.1028%;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43.9252%;\"\u003e\n \u003cp\u003eTo assess the ability to perceive limb motion in space\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eClinical assessments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eClinical motor assessments will include the\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eFugl-Meyer Assessment-Upper Extremity (FMA-UE)\u003csup\u003e26\u003c/sup\u003e\u0026nbsp; which provides quantitative measures of sensory and motor impairments in the upper limbs. The FMA-UE is scored from 0-66 and has been recommended by the International \u003cem\u003eStroke Rehabilitation\u003c/em\u003e and \u003cem\u003eRecovery Roundtable as a core measure\u003c/em\u003e\u003cem\u003e\u003csup\u003e41\u003c/sup\u003e\u003c/em\u003e\u003cem\u003e.\u0026nbsp;\u003c/em\u003eThe Action Research Arm Test (ARAT) assesses motor performance of the upper limb\u003csup\u003e42\u003c/sup\u003e. It consists of 19 tasks across the 4 subscales (grasp, grip, pinch, gross movement). The Wolf Motor Function Test (WMFT) evaluates the motor ability of the upper limbs during 15 timed function-based tasks and 2 strength-based tasks\u003csup\u003e43\u003c/sup\u003e. Maximum voluntary grip strength with the Jamar dynamometer will be used as a conventional measure of muscle strength in the upper limb post-stroke\u003csup\u003e44, 45\u003c/sup\u003e. \u0026nbsp;Pulp-to-pulp pinch strength will be assessed using a pinch gauge (B \u0026amp; L Engineering)\u003csup\u003e46\u003c/sup\u003e. The Box and Block Test (BBT) will be used to assess gross manual dexterity\u003csup\u003e47, 48\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical somatosensory assessments will include the Tactile discrimination test (TDT) which evaluates the ability to discriminate differences\u0026nbsp;in finely graded texture surfaces\u003csup\u003e49, 50\u003c/sup\u003e. The Functional Tactile Object Recognition Test (FTORT) assesses the ability to match everyday objects which have selected sensory attributes such as crushability, texture, shape, weight, size, and temperature. It also assesses functional movements through the sense of touch\u003csup\u003e51\u003c/sup\u003e. The Wrist Position Sense Test (WPST) evaluated proprioception, quantifying the participant\u0026rsquo;s ability to determine wrist position after an imposed movement involving flexion-extension and ulnar-radial deviation\u003csup\u003e52\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eOther assessments will include the evaluation of fatigue and pain. The Fatigue Assessment Scale (FAS) is a 10-item self-rated scale and will be used to evaluate physical and mental symptoms of chronic post-stroke fatigue\u003csup\u003e53\u003c/sup\u003e. The pain visual analogue scale (PVAS) is a single-item scale ranging from 0 (no pain) to 10 (excruciating pain)\u003csup\u003e54-56\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe assessments are summarized in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3. Assessments\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInstrument\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAssessment type: measurement domain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eICF domain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eScreening measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFunctional Independence measure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003eClinician reported: disability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eMontreal Cognitive Assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eRey Copy Figure Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: Cognition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFugl-Meyer Assessment-Upper Extremity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: Motor and somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody function and structure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eTactile Discrimination Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eLaboratory measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eKinarm standard tests\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: somatosensory-motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical measures\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFugl-Meyer Assessment-Upper Extremity (FMA-UE)\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: Motor and somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody function and structure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eAction Research Arm Test (ARAT)\u003csup\u003e42\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eWolf Motor Function Test (WMFT)\u003csup\u003e43\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eGrip strength (Jamar dynamometer)\u003csup\u003e44, 45\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eBox and Block Test (BBT)\u003csup\u003e47, 48\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003eObserver: motor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eTactile Discrimination Test (TDT)\u003csup\u003e57\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eWrist Position Sense Test (WPST)\u003csup\u003e52, 58\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFunctional Tactile Object Recognition Test (FTORT)\u003csup\u003e59\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003ePerformance: somatosensory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eBody functions and structures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eFatigue Assessment Scale (FAS)\u003csup\u003e53\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003eParticipant reported: fatigue in daily life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity and participation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003eStanford Fatigue Visual Analogue Scale (SFVAS)\u003csup\u003e60\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003eParticipant reported: mental and physical fatigue*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity and participation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 38px;\"\u003e\n \u003cp\u003ePain Visual Analogue Scale (PVAS)\u003csup\u003e61\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003eParticipant reported: pain*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eActivity and participation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e*Also measured pre and post treatment sessions and pre and post outcome assessment sessions\u003c/p\u003e\n \u003cp\u003eSFVAS: fatigue(VAS4\u0026ndash;10); no/minimal fatigue (VAS: 0\u0026ndash;3)\u003csup\u003e62\u003c/sup\u003e ; FAS: fatigue \u0026ge;24\u003csup\u003e63\u003c/sup\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTiming of outcome assessments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe participants will be tested at the start and end of the baseline phase, at post-intervention and at 1-month follow-up. The outcome assessments will be conducted on two consecutive days (assessment session 1: laboratory assessments-1.5 hours, assessment session 2: clinical assessments-1.5 hours).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBlinding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe participants will be blinded to the hypotheses being tested in this study i.e the participant will not be informed about the feasibility testing of the iCOSMO training intervention. The participants will also not be informed which amongst the two interventions is the experimental or control interventions, respectively. This is important so as to control for the psychological effects associated with knowing group assignments. Participant blinding will reduce bias in this study with regards to their behaviour in this study, altered attitudes, compliance, cooperation, attendance and response to the outcome measures\u003csup\u003e64, 65\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eMeasurements will be performed by a blinded assessor therapist who has received training in use of assessments (different to the therapist delivering treatment). The assessor and statistician will be blinded to the hypotheses and group assignment. Unblinding of the assessor will not be allowed at any time point.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical considerations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data collected during this study will be confidential. All personal information will be removed from the data and will be replaced with a number. A list linking the number with participants\u0026rsquo; names will be kept by the study team in a secure place, separate from the data file. \u0026nbsp;Only key staff members will have access to the study data.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eProtocol modification\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn case of any important modification of the protocol including assessments or eligibility criteria, a formal amendment will be undertaken and approval will be required from the University Health Network Research Ethics Board before implementation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA ANALYSIS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFeasibility\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eFeasibility data will be reported using descriptive statistics. The iCOSMO intervention will be considered feasible if the measures of fidelity achieve at least 70% of the targeted amount of practice and adherence to overall treatment.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eBaseline\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eDemographic variables will be analysed using standard descriptive methods, tested for normality using Shapiro-Wilks tests, and reported by treatment group. Categorical variables will be reported as frequency count (percentage), normally distributed continuous variables as mean (standard deviation) and ordinal and non-normally continuous variables as median (interquartile range). To identify any possible covariate imbalances between iCOSMO and GRASP groups, and possible randomization stratification levels in future full-scale trials, the variance ratios and empirical cumulative density functions (eCDFs) will be compared between treatment groups for key covariates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe stability of outcomes across the baseline phase was evaluated against two criteria: 1) absence of trend (almost flat) in raw scores across the two baseline timepoints when visually assessed; and 2) a variation of \u0026lt;5% was considered as an indication of stability during the baseline phase based upon recommendations for reproducibility studies\u003csup\u003e66, 67\u003c/sup\u003e. Stability across the baseline will indicate that the participant\u0026rsquo;s performance on outcome measures is not changing due to spontaneous recovery.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eWithin and between group differences\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe mean (SD) or frequency count (percentage) for outcome measures will be reported by treatment group for each time point they are administered. Change scores will report the mean change (SD of the change) in the outcome variables by group between 1) Baseline and post-intervention, 2) between baseline and 4-weeks follow-up post-intervention, and 3) between post-intervention and 4-weeks follow-up post-intervention. Morris G will assess effect size of the mean changes for the 3 time-points and an effect size of 0.8 will be determined to be a large effect\u003csup\u003e68\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFor continuous outcome measures between group analyses comparing scores at Time 1 (baseline) and Time 2 (post intervention), repeated measures ANCOVA\u0026nbsp;will be performed if the data is normally distributed. For non-normally distributed data, the Friedman Test will be performed. A secondary analysis with 3 time points (at baseline, post-intervention and follow-up), a linear mixed effects method model will be performed with random effects.\u003c/p\u003e\n\u003cp\u003eSince changes in performance in the outcome assessments across the group will include participants with varied nature of their deficits and levels of severity, it is also proposed that exploratory sub-analysis of changes in performance is conducted for participants with similar deficits and levels of severity. If possible, the characteristics of responders and non-responders will be investigated through uni- and multivariable regression analysis. As these are exploratory subgroup analyses, estimates and standard errors will be reported to provide indication of strength, direction and precision of the covariates effect on outcome measures and p-values will not be reported.\u003c/p\u003e\n\u003cp\u003eMissing data will be assessed. As less than 5% of data will be assumed to be missing and Missing Completely at Random (MCAR), intention-to-treat principle will be applied to all analyses for any missing data. Analyses will be conducted using STATA version 18 for Windows, SAS 9.4 for Windows, and R version 4.2. A p-value \u0026lt; 0.05 will be used to indicate statistical significance for all analyses. To correct for multiplicity of testing, a false discovery rate correction will be applied and adjusted p-values will be reported.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eImprovements in Kinarm standard task performance will be considered clinically meaningful if there is a change from an impaired to a normal overall task score. By comparing to a normative dataset, participants who receive a task score of \u0026ge; 1.96 are classified as having impaired upper extremity function, and those who receive a task score of \u0026lt; 1.96 are considered to have normative upper extremity function\u003csup\u003e69\u003c/sup\u003e. Improvements in clinical outcome measures will be considered meaningful if the changes reach or exceed the minimally clinically important difference.\u0026nbsp;\u003c/p\u003e"},{"header":"EXPECTED RESULTS","content":"\u003cp\u003eIt is expected that the ICOSMO intervention will be feasible and beneficial in delivering a personalised, progressive, high intensity repetition intervention combining cognitive, somatosensory and motor training in an integrated manner amongst stroke survivors. The iCOSMO study may also show that it is feasible to individualise the intervention tasks to the nature and severity of upper limb deficits. Participants are expected to achieve the target number of repetitions and time of exposure to tasks which has been evidenced to be feasible by Birkenmeier et al (2010)\u003csup\u003e19\u003c/sup\u003e. It is expected that participants will attend at least 75% of the intervention sessions\u003csup\u003e70\u003c/sup\u003e. It is possible for fatigue and pain to be higher at the end of the intervention session as compared to the beginning. However, the magnitude of the scores is expected to be relatively low. Consequently, we do not expect fatigue or pain to limit participation or adherence to the iCOSMO intervention.\u0026nbsp;It is anticipated that the recruitment target of 40 participants will be achieved since this target is within the recruitment capability for each site we will be utilizing (30 participants per site per year).\u003c/p\u003e\n\u003cp\u003eIt is also expected that the iCOSMO training intervention will improve the arm and hand function of stroke survivors. We anticipate that participants will improve from baseline to post-intervention on all outcome measures evaluated in the iCOSMO trial. Additionally, improvements in performance scores on the robotic laboratory assessments, FMA-UE and the ARAT are anticipated to be similar to the minimally clinically important difference. We expect the gains in arm and hand function to be retained at the one-month follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLIMITATIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeveral limitations need to be considered in this research proposal. This study has low statistical power, which will limit the external generalisability of the results. This will also limit the ability to conduct further statistical analyses to examine individual factors such as nature and severity of deficits within the sample. Future studies that have sufficient statistical power with larger sample sizes are required to further explore the efficacy of the iCOSMO intervention and its impact on upper limb deficits and severity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study follows a stepwise and systematic approach for the development and evaluation of a complex intervention post-stroke, which emphasizes the importance of Phase 2 studies prior to a larger RCT\u003csup\u003e71\u003c/sup\u003e. In the future, a larger RCT comparing varied doses of iCOSMO required to maximize arm and hand recovery after stroke.\u003c/p\u003e\n\u003cp\u003eWe also do not know whether the target of 225 repetitions and time of exposure (per session) is optimal. Similarly, we do not know whether 36 hours or 18 sessions of iCOSMO intervention are ideal. The target of 70% fidelity and adherence is also arbitrary. This proposed work will lay down the groundwork needed before making comparisons with regards to dosage, intensity, and timing of training, first providing information on the potential benefits of higher doses, fidelity and adherence. The data from this study should be viewed as the start of an exploration of how personalised components of the intervention and dosage could be manipulated to optimise upper limb recovery.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study will be the first to demonstrate whether it is both feasible and beneficial to deliver a personalised, progressive, high intensity repetition intervention integrating cognitive, somatosensory, and motor training in one protocol. Additionally, this proposed study will contribute to the literature on priming strategies as a restorative means of targeting neural mechanisms to reduce upper limb deficits post-stroke. It will help better understand the coupling action between cognitive, somatosensory, and motor training in task performance. Consequently, this project will directly advance knowledge in the field of upper extremity recovery following stroke.\u003c/p\u003e \u003cp\u003eThe systematic stepwise development of the iCOSMO intervention will inform about the design of the intervention with regards to the choice of active ingredients of the multiple components that can optimise the intervention, the complex interactions between them, their targets, and mechanisms of action so as to enhance upper limb recovery post-stroke. If the preliminary effects are beneficial, this study will contribute to better understanding of the mechanisms underlying cognitive, somatosensory, and motor learning-related neuroplasticity. If found to be both feasible and beneficial, this study will then also have laid down the groundwork needed before taking future steps towards a larger RCT of iCOSMO. This project also has the potential to help stroke survivors regain upper extremity faster than currently possible by cognitive, somatosensory, and motor training delivered separately. Improved arm and hand function will enhance participation and productivity for the estimated 400,000 stroke survivors in Canada and reduce burden on care providers.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe iCOSMO training intervention aims to simultaneously deliver cognitive, somatosensory, and motor rehabilitation to better restore arm and hand function in stroke survivors. If effective, the widespread implementation of the iCOSMO training intervention has the potential to increase arm and hand function in stroke survivors around the world, improving quality of life and the capacity to return to work, leisure, and family roles. Additionally, by improving treatment outcomes, the iCOSMO training intervention has the potential to lessen the global burden of stroke on the healthcare system, reducing inpatient stay times for survivors, in turn saving millions of dollars annually.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n \u003cli\u003eEthics approval and consent to participate:\u0026nbsp;The study was approved by the University Health Network Research Ethics Board (22-5628). All participants will provide written informed consent, prior to participation in this study, according to the Declaration of Helsinki.\u003c/li\u003e\n \u003cli\u003eConsent for publication: Not applicable\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials: Not applicable\u003c/li\u003e\n \u003cli\u003eCompeting interests:\u0026nbsp;The authors report there are no competing interests to declare.\u003c/li\u003e\n \u003cli\u003eFunding: StrokeCog post-doctoral fellowship\u003c/li\u003e\n \u003cli\u003eAuthors' contributions: UG has led all stages of this study, including development of the intervention, development of the protocol and writing and reviewing the manuscript. LL has provided statistical guidance and reviewed the manuscript. MB has contributed to the development of the protocol and reviewed the manuscript.\u003c/li\u003e\n \u003cli\u003eAcknowledgements: We would like to thank Dr Sean Dukelow from the University of Calgary, Koloman Varady and Anne Vivian-Scott from BKIN technologies Ltd for their contributions to the kinarm training tasks\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLang CE, Bland MD, Bailey RR, Schaefer SY, Birkenmeier RL. Assessment of upper extremity impairment, function, and activity after stroke: foundations for clinical decision making. J Hand Ther. 2013;26(2):104-14;quiz 15.\u003c/li\u003e\n \u003cli\u003eKwakkel G, Kollen BJ, van der Grond J, Prevo AJ. Probability of regaining dexterity in the flaccid upper limb: Impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34(9):2181-6.\u003c/li\u003e\n \u003cli\u003eCarey L, Matyas T. Frequency of discriminative sensory loss in the hand after stroke. 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Use of the Box and Block Test for the evaluation of manual dexterity in individuals with central nervous system disorders: A systematic review. Manual Therapy Posturology Rehabilation Journal. 2016;14.\u003c/li\u003e\n \u003cli\u003eCarey LM. Somatosensory Loss after Stroke. 1995;7(1):51-91.\u003c/li\u003e\n \u003cli\u003eCarey L. Tactile and proprioceptive discrimination loss after stroke: Training effects and quantitative measurement. Melbourne: LaTrobe University; 1993.\u003c/li\u003e\n \u003cli\u003eCarey L, Nankervis J, LeBlanc S, Harvey L, editors. A new functional tactual object recognition test (fTORT) for stroke clients: Normative standards and discriminative validity. 14th International Congress of the World Federation of Occupational Therapists; 2006; Sydney, Australia.\u003c/li\u003e\n \u003cli\u003eCarey LM, Oke LE, Matyas TA. Impaired limb position sense after stroke: a quantitative test for clinical use. Arch Phys Med Rehabil. 1996;77(12):1271-8.\u003c/li\u003e\n \u003cli\u003eMead G, Lynch J, Greig C, Young A, Lewis S, Sharpe M. Evaluation of fatigue scales in stroke patients. Stroke. 2007;38(7):2090-5.\u003c/li\u003e\n \u003cli\u003eHawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 2011;63(S11):S240-S52.\u003c/li\u003e\n \u003cli\u003eRitter PL, Gonz\u0026aacute;lez VM, Laurent DD, Lorig KR. Measurement of pain using the visual numeric scale. J Rheumatol. 2006;33(3):574-80.\u003c/li\u003e\n \u003cli\u003eWilliamson A, Hoggart B. Pain: A review of three commonly used pain rating scales. 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Stroke. 1999;30(7):1357-61.\u003c/li\u003e\n \u003cli\u003eLogan A, Freeman J, Kent B, Pooler J, Creanor S, Vickery J, et al. Standing Practice In Rehabilitation Early After Stroke (SPIRES): A functional standing frame programme (prolonged standing and repeated sit to stand) to improve function and quality of life and reduce neuromuscular impairment in people with severe sub-acute stroke\u0026mdash;A protocol for a feasibility randomised controlled trial. Pilot and Feasibility Studies. 2018;4(1):66.\u003c/li\u003e\n \u003cli\u003eCumming TB, Mead G. Classifying post-stroke fatigue: Optimal cut-off on the Fatigue Assessment Scale. J Psychosom Res. 2017;103:147-9.\u003c/li\u003e\n \u003cli\u003eJ. PS. Clinical trials: A practical approach. Chichester, England: Wiley; 1983.\u003c/li\u003e\n \u003cli\u003eKaranicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: blinding: who, what, when, why, how? Can J Surg. 2010;53(5):345-8.\u003c/li\u003e\n \u003cli\u003eHopkins WG. Measures of reliability in sports medicine and science. Sports medicine (Auckland, NZ). 2000;30(1):1-15.\u003c/li\u003e\n \u003cli\u003eHopkins WG. A new view of statistics: Internet Society for Sport Science; 2000 [Available from: http://www.sportsci.org/resource/stats/.\u003c/li\u003e\n \u003cli\u003eMorris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organizational Research Methods. 2008;11(2):364-86.\u003c/li\u003e\n \u003cli\u003eSimmatis LER, Early S, Moore KD, Appaqaq S, Scott SH. Statistical measures of motor, sensory and cognitive performance across repeated robot-based testing. Journal of NeuroEngineering and Rehabilitation. 2020;17(1):86.\u003c/li\u003e\n \u003cli\u003eScianni A, Teixeira-Salmela LF, Ada L. Challenges in recruitment, attendance and adherence of acute stroke survivors to a randomized trial in Brazil: a feasibility study. Brazilian Journal of Physical Therapy. 2012;16:40-5.\u003c/li\u003e\n \u003cli\u003eBernhardt J, Hayward KS, Dancause N, Lannin NA, Ward NS, Nudo RJ, et al. A Stroke Recovery Trial Development Framework: Consensus-Based Core Recommendations from the Second Stroke Recovery and Rehabilitation Roundtable. Neurorehabil Neural Repair. 2019;33(11):959-69.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"Stroke, motor, somatosensation, upper limbs, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-6206942/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6206942/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Up to 85% of stroke survivors experience motor, somatosensory and cognitive deficits. Interventions that simultaneously stimulate motor, somatosensory and cognitive functions have the potential to maximize processes of neuroplasticity and optimise upper limb recovery after stroke. This study aims to investigate the feasibility of a personalised integrated COgnitive-somatoSensory-MOtor (iCOSMO) training intervention to improve upper limb recovery in people with chronic stroke. The objectives are: 1) to evaluate the feasibility, and 2) to determine the preliminary efficacy of the iCOSMO intervention in people with chronic stroke.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThe study design will be a prospective pilot randomised controlled trial with two-arms. We aim to recruit 40 adults with stroke (\u0026gt;6 months). The iCOSMO intervention will consist of a combination of haptic perception exploratory tasks that incorporate active touch and movement exploratory procedures, robotic training using the Kinarm Exoskeleton device, with a cognitive focus on the motor and sensory attributes of all of the tasks. iCOSMO will be goal-oriented and individualised to the nature and severity of upper limb somatosensory and motor deficits. The experimental group will receive a total of 36 hours of treatment over 6 weeks. The control group will receive a matched dose of a Graded Repetitive Arm Supplementary Program home-based motor exercise programme. Feasibility measures will evaluate the recruitment and adherence rates. Robotic assessments will be conducted using the Kinarm standard tasks™. Standardised clinical assessments will include the Action Research Motor Test and the Tactile Discrimination Test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study will be the first to demonstrate whether it is both feasible and beneficial to deliver a personalised intervention integrating somatosensory, motor and cognitive training in one protocol. The iCOSMO study may also show that it is feasible to individualise the intervention tasks to the nature and severity of upper limb deficits. It is also expected that the iCOSMO training intervention will improve the arm and hand function to a larger extent than the GRASP training in chronic stroke survivors. This proposed study will help better understand the impact of combining cognitive, somatosensory, and motor training in task performance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eThis trial was prospectively registered on Clinicaltrial.gov (NCT06498011) on July, 12th, 2024 and is available at https://clinicaltrials.gov/study/NCT06498011\u003c/p\u003e","manuscriptTitle":"An integrated COgnitive-somatoSensory-MOtor training intervention for upper limb recovery after stroke: Protocol for a Phase II randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-26 06:23:58","doi":"10.21203/rs.3.rs-6206942/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-07-14T18:24:44+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-04-24T09:12:50+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-18T00:07:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-13T09:07:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pilot and Feasibility Studies","date":"2025-03-11T16:54:53+00:00","index":"","fulltext":""}],"status":"published","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}}],"origin":"","ownerIdentity":"28ec00a8-ccb7-4f05-a1b1-a7aaebca718f","owner":[],"postedDate":"March 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-09T19:05:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-26 06:23:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6206942","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6206942","identity":"rs-6206942","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}