Resilience And Healthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomised, parallel group, placebo-controlled clinical trial protocol

Resilience And Healthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomised, parallel group, placebo-controlled clinical trial protocol | 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 Resilience And Healthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomised, parallel group, placebo-controlled clinical trial protocol Katherine Poulsen, Nicola Burton, Hannah Mayr, Veronique Chachay, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6552255/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background : The importance of self-management strategies that optimize physical health and mental health in the management of rheumatoid arthritis (RA) is recognized, but access to multidisciplinary teams to support this can be challenging. Furthermore, evidence for the impact of multidisciplinary interventions, especially in early RA, is lacking. Methods : The Resilience and Healthy Lifestyle for Rheumatoid Arthritis (RA-HEAL) Trial is a pragmatic RCT that aims to compare effects of a structured multidisciplinary lifestyle intervention with self-directed activities in best-practice usual care. The 20-week multi-modal intervention incorporates structured resilience training conducted by a clinical health psychologist (CHP), followed by an exercise physiologist (EP)-led exercise program, dietary education conducted by a dietitian nutritionist (DN), smoking cessation program (where applicable) and psychologist-led behavior-change support. The comparison group will receive written information on healthy lifestyle in accordance with standard best practice care. The primary outcome is health-related quality of life (QoL) at 6 months. Discussion : RA-HEAL tests whether a tailored intervention including formal resilience training with a clinical psychologist followed by Mediterranean diet, exercise, smoking cessation and behavior change support has a greater effect on health-related QoL at 6 months, than written advice given in current best-practice settings. QoL is a composite endpoint that is highly valued by patients with RA. RA-HEAL is unique in it targets RA within 12 months of onset. RA-HEAL’s linkage with the Australian Autoimmune Arthritis Biobank Cooperative (A3BC) supports 6 monthly follow-up data and biosampling to 24 months post-intervention and linkage to health data collections, creating a valuable resource for future research and the potential to determine medium and long-term effects of behavior change. In its secondary outcomes, RA-HEAL will analyze the longevity of effects of intervention or best-practice usual care for up to 2 years, and cost utility. The outcomes should provide evidence to underpin a scalable approach to support people with newly-diagnosed RA. Trial registration : ACTRN12625000050459, ANZCTR Rheumatoid arthritis lifestyle intervention diet exercise behavior change resilience training biosamples quality-of-life Figures Figure 1 Figure 2 Figure 3 Administrative information Title {1} R esilience A nd Hea lthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomized, parallel group, placebo-controled clinical trial protocol Trial registration {2a and 2b} ACTRN12625000050459, ANZCTR Protocol version {3} 1.3, 12 March 2025 Funding {4} Medical Research Future Funder (MRFF) Clinician Researchers - Applied Research in Health ID: 2032246 Author details {5a} Katherine A Poulsen, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, The Prince Charles Hospital, Chermside QLD 4032 Australia, The Royal Brisbane and Women’s Hospital QLD 4029 Nicola W Burton, School of Applied Psychology, Griffith University, Brisbane, QLD 4111 Australia Hannah L Mayr, Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia; and Faculty of Health Medicine and Behavioural Sciences, University of Queensland, Brisbane, QLD 4072 Australia Veronique Chachay, Frazer Institute, The University of Queensland, Woollongabba, QLD 4102 Australia. Jeff Coombes, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072 Australia. Amee Sonigra, Department of Rheumatology, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia, Paul Christensen, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Karl Hansford, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Dianna J Ang, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Jessica Neri, The Arthritis Movement, PO Box 2121, Lutwyche, QLD, 4030 Ramali Mendis, Department of Rheumatology, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia, Tom Lynch, Institute of Bone and Joint Research, The Australian Arthritis and Autoimmune Biobank Collaborative, Kolling Institute, The University of Sydney, St Leonards NSW 2065, Australia, Cheryl Dines, The Arthritis Movement, PO Box 2121, Lutwyche, QLD, 4030 Helen Benham, The University of Queensland Faculty of Health, Medicine and Behavioural Sciences and Princess Alexandra Hospital Woolloongabba, QLD 4102, Australia Aoife Sweeney, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Lyn M March, Institute of Bone and Joint Research, The Australian Arthritis and Autoimmune Biobank Collaborative, Kolling Institute, The University of Sydney, St Leonards NSW 2065, Australia, Asaduzzaman Khan, School of Health and Rehabilitation Sciences The University of Queensland, Brisbane QLD 4072 Australia Haitham Tuffaha, Centre for the Business and Economics of Health, The University of Queensland, Brisbane QLD 4072 Australia Ranjeny Thomas, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Australia Name and contact information for the trial sponsor {5b} The University of Queensland Associate Director, Research Commercial Management Brisbane, QLD 4072 Role of sponsor {5c} Sponsor provides all information about the intervention to the Principal Investigator (PI) to conduct the study; Prepares and submits all required documentation to obtain study approval and initiation; Implement and maintains quality assurance and quality control systems for conduct and data generation in the study; Registers the study on the appropriate clinical trials registry; Designates appropriately qualified personnel to advise on study-related medical questions or problems; Notifies the HREC of trial cessation or any adverse events. Introduction Background and rationale {6a} Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune arthritis. In Australia, it affects up to 1.5% of people and is estimated to account for 16% of the total burden of disease for all musculoskeletal conditions, with an estimated $966.1 million spent on its management (1, 2). Etiology involves genetic and environmental risks, with an estimated population-attributable risk of potentially-modifiable health factors of 40% (3). The importance of personalized health care and multidisciplinary programs to support self-management of rheumatoid arthritis (RA) is increasingly recognized. These are empowering for patients, improving both physical and mental health. Multi-disciplinary programs t for self-management can be presented in a variety of ways including individual, group and online platforms. Despite international consensus on the importance of this as standard of care, inadequate support for self-management, particularly access to multidisciplinary care, is a common issue across many health services (1, 4). In Australia, access to multidisciplinary teams varies across hospitals and health services. In the community, general practitioners coordinate health care plans for patients with eligible chronic health conditions which allows for just five Medicare rebates per calendar year across all allied health services. Using the Medicare rebate, many service providers still charge gap payments which may present financial barriers (5). Besides these barriers, in some services such as psychology, demand for services may far outstrip supply (6). In combination, these factors can present barriers to access for patients. Several small randomized controlled trials (RCT) have assessed the impact of multidisciplinary interventions in people with RA. The ‘Plants for Joints’ RCT (n=83) enrolled patients with longstanding RA and low-moderate disease activity into a 16-week lifestyle program which incorporated a whole-food plant-based diet, physical activity and stress management. This study commenced with a dietary and physical activity component, which was followed by a stress-management component consisting of psychoeducation on the effects of stress on health, stress management and guided exercises on breathing, visualisation and relaxation techniques supported by podcasts and videos (7, 8). The intervention led to greater improvements in body weight, glucose control, low density lipoprotein and Disease Activity Score (DAS28) than the usual care group over 16 weeks. The Mediterranean DiEt In Rheumatoid Arthritis (MADEIRA) RCT (n=40) included personalised dietary planning based on the Mediterranean diet, cooking tips and demonstration, and group discussion on physical activity, stress management, relaxation and sleep hygiene in a 12-week intervention in women with RA >2 years duration and found improved DAS28 and reduction in Body Mass Index (BMI) post-intervention. The personalized Mediterranean diet plan and advice on physical activity was supported through nudges by a computer-based clinical decision support systems platform(9). Another RCT demonstrated that the Mediterranean diet combined with exercise improved health-related quality of life (QoL) and functional ability in women with longstanding RA of many years’ duration, compared to control or Mediterranean diet alone (10, 11). In a systematic review, Mediterranean diet had beneficial effects in people with RA across inflammation, disease activity and CVD risk profile (12). A small RCT (n=51) comparing the Mediterranean diet to Western diet in patients with RA of >2 years duration demonstrated improvement in health related QoL (SF-36 vitality score) and DAS28 score over a 12 week intervention period (13). Another controlled, non-randomised study (n=130) of a 6-week Mediterranean diet intervention in women with longstanding RA identified improved pain scores, patient global and function but not DAS28 in the intervention group (14). No RCT has assessed the effects of a multidisciplinary intervention that combines dietary, exercise, smoking cessation, psychological and behavior change support components. Furthermore, there is a need to explore these approaches in newly diagnosed RA. The Resilience and Healthy Lifestyle for Rheumatoid Arthritis (RA-HEAL) Trial is a pragmatic RCT that aims to compare a structured multidisciplinary lifestyle intervention with self-directed activities in best-practice usual care. The structured intervention in RA-HEAL is designed to provide participants with an integrated multi-disciplinary approach to promote health self-efficacy, to enhance resilience, implement medical management and reduce the need to coordinate multiple practitioners to assist with wellbeing and lifestyle changes in smoking, exercise and diet quality. In a pilot intervention we found that the 4-month multidisciplinary resilience followed by healthy lifestyle (diet, exercise, behavior change support) program enhanced the confidence and capability of people with longstanding RA to self-manage RA, with benefits in wellbeing, diet quality, physical function, DAS28, BMI and Quality of Life (QoL)(15). Unlike previous studies, this trial is targeting people with early RA, who have received a diagnosis within the past 12 months, since the early stages of RA represent a window of opportunity for downregulation of inflammation, and the potential to change disease trajectory in the long term (16). Objectives { 7} The aim of this trial is to assess the feasibility, effectiveness, acceptability and durability of a structured, multidisciplinary, multicomponent resilience and healthy lifestyle (smoking cessation, nutrition, exercise) intervention to improve health self-efficacy and QoL among people with early RA. Our primary objective is to determine whether RA-HEAL intervention improves health-related QoL relative to usual best practice care at 6 months post intervention. Secondary objectives include whether, relative to best practice usual care, and at 6-24 months post intervention, RA-HEAL intervention: Is feasible, acceptable and safe for participants Improves mental health, physical activity and function, diet quality, and (where indicated) smoking cessation/confidence, as well as overall health related QoL up to 24 months. Improves participant efficacy for RA self-management Increases likelihood of attaining and maintaining DAS28-remission in the first 2 years after diagnosis Represents value for money Our primary hypothesis is that RA-HEAL intervention improves health-related QoL relative to best practice usual care at 6 months post-intervention, as determined by the physical health component score within the standardized QoL questionnaire, 36-item Short Form Survey version 2 (SF-36 v2). Our secondary hypotheses are that at 6-24 months post-intervention, relative to best practice usual care, that RA-HEAL intervention improves: Participant efficacy for self-management Muscular fitness and exercise capacity Diet quality Duration of smoking cessation RA disease activity Duration of RA remission Cardiovascular disease risk profile Mental health Overall health related quality of life Trial design {8} RA-HEAL is an open-label pragmatic randomised controlled trial. The trial has been designed to compare a structured, multidisciplinary, multicomponent resilience and healthy lifestyle program (Program A) with the provision of multicomponent written lifestyle advice as part of best practice usual care (Program B) in people with early RA. Both programs focus on subjective wellbeing and a healthy lifestyle, including exercise, healthy eating and (if indicated) smoking cessation (Figure 1). Eligible participants will be randomly allocated to Program A or Program B. RA-HEAL will recruit people with early RA who are willing and motivated to commit to a 20-week multi-modal intervention with the potential for regular online and face-to-face interventions with a multidisciplinary team. Participants must also be willing to be enrolled in the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), a national musculoskeletal and autoimmune disease biobanking network that facilitates the sharing and storage of data and biospecimens for ethics-approved, open-access research into arthritis and autoimmune conditions (17, 18).Data and biospecimens for this trial will be managed using the A3BC platform. Methods: Participants, interventions and outcomes Study setting { 9} RA-HEAL will be undertaken in the greater Brisbane metropolitan area of Australia, centered on the City of Brisbane and including the Ipswich and Logan areas of Greater Brisbane. Eligible participants will remain under the care of their usual treating rheumatologist and usual general practitioner (GP). The interventions for Program A participants will be offered at 4 study locations within Greater Brisbane. Eligibility criteria {10} Inclusion criteria Adults with RA who are at least 18 years old. RA onset in the last 12 months, diagnosed according to ACR/EULAR 2010 Classification Criteria (19), managed by a rheumatologist with conventional or biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) Residing in Greater Brisbane Area, including Ipswich and Logan Willing and able to access and participate in individual and group program sessions (in-person and online) as an adjunct to continuing their RA treatment with their usual rheumatologist. Ambulatory and cleared for participation in an exercise program by a medical practitioner. Willing to be concurrently enrolled in A3BC. Able to speak and understand English at a level capable of understanding the informed consent process as determined by the principal investigator. Exclusion criteria Medical conditions contraindicated to exercise training (e.g. unstable angina) Current or intended attendance in a program promoting RA self-management Currently receiving psychiatric, psychological or counselling treatment Significant lower limb musculoskeletal impairment preventing stationary cycling Who will take informed consent? {26a} After initial contact with potential participants, the research team will use the approved recruitment script to facilitate conversations. Prospective participants will attend a telehealth/online screening visit with the PI (or delegated staff member). For those participants providing verbal consent, the consent process will be clearly documented in the patient’s medical record as per standard practice. Additional consent provisions for collection and use of participant data and biological specimens {26b} Written consent will be completed in person at the RA-HEAL-A3BC baseline visit at the Princess Alexandra Hospital Clinical Research Facility. Participants not previously enrolled in A3BC will be required to first sign the A3BC consent form. Consent to A3BC includes permission to collect and biobank biological samples (blood, oral swab and faeces). After consent to the RA-HEAL trial, which includes access to usual care routine blood work, a letter will be sent from the PI to the participant’s treating rheumatologist and general practitioner advising them of their patient’s participation in RA-HEAL and requesting access to rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), as well as lipid profile and C-Reactive Protein (CRP) concomitant with each visit. Recruitment {15} Participants will be recruited via information and promotional notices provided through rheumatologists, consumer support organizations such as The Arthritis Movement (20) and various media. Coordinators will also invite RA HEAL-eligible participants already enrolled in A3BC. Withdrawal Participants can withdraw from RA-HEAL at any time without having to give a reason. If participants choose to withdraw they will be provided with a withdrawal form to sign. If a participant withdraws from RA-HEAL, separate withdrawal from A3BC will be discussed. Under such circumstances, they may optionally stop actively participating but allow for their samples and data already in the biobank to continue to be used in research, or disallow further use of their samples, and request that their samples and data are destroyed. Interventions Explanation for the choice of comparators {6b} Both the European League of Rheumatology EULAR and the American College of Rheumatology (ACR) recommend that patients with rheumatic diseases are educated about the benefits of managing stress and lifestyle improvements including a healthy diet, regular exercise and encouragement to quit smoking (21, 22). The comparator group will receive usual best practice care, which incorporates the provision of advice on recommended lifestyle modifications. Intervention description {11a} STUDY ARMS: all participants At the baseline assessment, all participants will receive written lifestyle advice information sheets from Arthritis Australia (Arthritis and Emotional Wellbeing; Exercise and RA; Healthy Eating and Arthritis; Physical Activity Arthritis Information Sheet; 10 Steps For Living Well With Arthritis) (23), as well as from the Australian Rheumatology Association (ARA) (Things You Can Do to Manage Your Rheumatoid Arthritis (24)); The Quitline for smoking cessation, and The Arthritis Movement contact details for support and exercise programs (20), with questions answered verbally by the PI. All participants will receive a diary in which to record adverse events, such as injuries. STUDY ARMS: PROGRAM A: RA-HEAL INTERVENTION Program A participants will take part in the RA-HEAL intervention. It will be delivered over 5 months, comprising five partially overlapping multidisciplinary person-centered interventions designed to recognize individual preferences, values, and concerns; with shared decision making, empowerment, and physical and emotional support, with some basic resources provided. Program A will be delivered as a combination of one-on-one or group in-person and videoconference sessions (Figure 2). In-person sessions will be delivered at four sites (Princess Alexandra Hospital, Ipswich Hospital, the University of Queensland St Lucia campus, and Griffith University Nathan campus), with oversight from A/Prof Nicola Burton (CHP), Dr Hannah Mayr (DN), Prof Jeff Coombes (EP, and Prof Coral Gartner (tobacco treatment specialist). Participants will be able to select their preferred in-person group location and time from the multiple time options offered and will be encouraged to attend the sessions at the same site throughout the intervention phase. Online and in person groups will be capped at 10 people. Participants will complete the full intervention schedule of resilience, exercise training, nutrition, smoking cessation and behavior change support over a 20-week period. Multidisciplinary Intervention 1. :- Resilience This group component is scheduled at the beginning to introduce key wellbeing concepts over the first eight weeks of the intervention. Each week participants will attend both an onsite group session and an online group session. It aims to provide support on adjustment to RA, and to provide a foundation for coping strategies relevant across the other components. Drawing from Acceptance and Commitment Therapy, Cognitive Behavior Therapy and Behavior Activation principles, sessions will focus on the role of mental health in RA self-management, mindfulness, acceptance, cognitive flexibility, coping strategies, life values and meaningful actions, social support, and sleep. Sessions will include information giving, personal reflection, experiential activities, skill rehearsal, feedback and problem-solving and applied practice “homework”. A written handbook on session content and activities will be provided. Multidisciplinary Intervention 2. :- Exercise Training The twelve-week exercise training component will commence in week 9. Initially a 1-hour individual session will determine participants’ exercise capacity, muscular fitness, exercise goals and preferences. Their individualized exercise prescription will be based on medical history, interests/preferences, physical capacity, and suitability for self-direction. Participants will then attend group exercise training sessions, within a mixture of weekly onsite and online group sessions. Each session will target recommendations of ≥150 minutes/week of moderate to vigorous aerobic and muscle strengthening exercise. Aerobic exercise will focus on walking unless significant lower limb musculoskeletal impairment preventing walking or stationary cycling, in which case suitable alternatives will be identified based on participant capabilities and access to resources. Strength exercises will involve upper and lower limbs using body weight and provided Therabands and small weights for use on site and at home. A Fitbit will also be provided to participants to facilitate self-monitoring. Multidisciplinary Intervention 3. :- Nutrition The nutrition intervention will also commence in week 9 and will run over twelve weeks. Initially, a 1-hour individual participant consultation will assess nutrition and set personalized goals. This will be followed up with two further 30-minute individual consultations and also three 1-hour group sessions that provide nutrition education and practical strategies, related to swapping or replacing foods, food preparation and recipes, label reading, shopping and eating out. Counselling will recommend alignment with principles of a Mediterranean-style diet (25, 26), including promoting higher intake of foods with anti-inflammatory properties (vegetables, fruits, nuts and seeds, legumes, fish and seafood, whole grain breads and cereals, herbs/spices, extra virgin olive oil), moderate intake of unflavored dairy foods, poultry and eggs, and lower intake of pro-inflammatory or ultra-processed foods including processed meats, red meat, sugary drinks, and other packaged or commercial foods and drinks high in saturated fat, sugar and/or sodium. Recommendations will be foods-focused to promote overall diet quality without a specific target macronutrient profile. The recommendations will be individualized and tailored; evidence-based resources and recipes which align with the Mediterranean-style diet principles (e.g. from Queensland Health Nutrition Education Materials Online and National Heart Foundation) will be provided where appropriate. Multidisciplinary Intervention 2. :- Smoking Cessation Participants who smoke will also commence a seven-week smoking cessation program, in week 9. Initially, a group education session will be offered. This will be followed by weekly individual consultations. Sessions will include nicotine dependence assessment, quitting self-efficacy, lung age calculator, individual Quit Plan, education, support, and practical coping strategies. Over-the-counter stop smoking Nicotine Replacement Therapy options will be recommended and demonstrated. Dosing is based on World Health Organization “first line therapy” and Royal Australasian College of General Practitioner guidelines, including combination patches plus oral nicotine replacement, which is one of the most successful approaches to quit smoking (27). Prescription Varenicline and Bupropion options will be supported in line with participant preferences, in consultation with the participant’s usual GP. Multidisciplinary Intervention 4. :- Behavior Change Support Behavior change support sessions will be conducted during the final month of the intervention, starting in week 17. These sessions will be delivered by the same clinical/health psychologist who provided resilience training in week 1 of the intervention. They will focus on integrating wellbeing and healthy lifestyle activities into everyday life, and responding to related challenges. Content is based on the 5A Counselling Framework, which is an evidence-based approach appropriate for chronic conditions and endorsed by the RACGP and US Task Force on Preventive Health Care. The key components of the 5A framework include: Assessment : change experiences/barriers/enablers Advice : clear recommendations for change Agree : Collaborative agenda setting Assistance : Cognitive and behavioral change strategies as indicated e.g. motivational interviewing, goal setting, action planning, positive expectations, problem-solving, self-monitoring, social support, self-talk Arrange : Additional assistance/resources as relevant. At the completion of the intervention period, participants will be invited to attend an online focus group to discuss intervention experiences and associated barriers and enablers to engagement in the interventions. STUDY ARMS: PROGRAM B: ONGOING BEST PRACTICE USUAL CARE Participants in Program B will receive brief monthly check-ins by email to inform of appointment times for follow-up and to monitor AEs. Participants will be referred to their general practitioner or rheumatologist should they need further management. Criteria for discontinuing or modifying allocated interventions {11b} n/a Explanation: This study does not trial any medicinal products and as detailed in the above intervention description, all components of the multidisciplinary intervention will be personalized to accommodate individual participants’ needs. Strategies to improve adherence to interventions {11c} One of the barriers to program adherence is the significant time commitment required. Details have been provided at informed consent and will be discussed verbally during screening. A support person (e.g. family member or friend) is encouraged to be at the consent meeting to assist with information retention. Letters to the participant’s treating rheumatologist and general practitioner will encourage support from other members of the health care team. The person-centred approach used in Program A (e.g. individualised exercise training and nutrition) is intended to take into account individual concerns and preferences and empower participant participation. Offering options for different times and locations for in-person interventions, including weekends, as well as some sessions via videoconference to reduce travel burden, are intended to facilitate adherence. Commencing with resilience is intended to provide intrapersonal strategies to assist with engagement to the lifestyle component. Relevant concomitant care permitted or prohibited during the trial {11d} Participation in RA-HEAL is considered an adjunct to a participant’s continuous medical care from their usual rheumatologist (once stable on conventional or biological DMARDs, appointments are typically every 3-6 months), general health care with their usual general practitioner and any additional support services and activities (including related to healthy eating, exercise, smoking cessation, wellbeing) initiated by them before or during the intervention period.. Provisions for post-trial care {30} After the trial all participants will continue to receive RA treatment with their usual rheumatologist, general health care with their usual general practitioner and any additional support services and activities initiated by them. Outcomes {12} The primary outcome is physical health-related QoL at 6 months, as determined by the SF-36 v2 physical component score. Secondary outcomes include: Physical health-related QoL : as well as the primary outcome of testing at 6 months, SF-36 v2 physical component score at 12, 18 and 24 months will also be measured Confidence for self-management of RA : the Perceived Competence Scales will assess confidence in taking an active role in managing wellbeing, exercise, healthy eating, medications and (if relevant) smoking cessation in the context of having RA at 6, 12, 18 and 24 months. Physical function and anthropometry: exercise capacity (6-Minute Walk Test (6MWT)), neuromuscular strength (grip strength with a dynamometer), power (Timed-Up & Go (TUG) test) and strength endurance (5 times sit to stand test and 30 second arm curl test), gait speed (4 metre walk test) and balance (single leg balance test); height, weight, and waist circumference at 6, 12, 18 and 24 months. Mental health: SF36v2 mental health component score, the Warwick-Edinburgh Mental Wellbeing Scale and the Perceived Stress scale at 6, 12, 18 and 24 months. Physical activity : physical activity and sedentary behavior will be assessed; (i) objectively via Actigraph accelerometry over one week at baseline and at 6 months, and (ii) by self-report using items from the National Health Survey at 6, 12, 18 and 24 months (28). Diet quality : the 50-item Mediterranean Diet and Culinary Index (MediCul) at 6, 12, 18 and 24 months, to provide a score between 0 to 100 (29). The tool also allows for calculation of a commonly reported validated 14-item Mediterranean diet adherence score (30). Smoking cessation : self-report at 6, 12, 18 and 24 months, (7-day and continuous abstinence), including number of cigarettes smoked, nicotine dependence, quitting self-efficacy i.e., self-confidence about making another quit attempt (if quit attempt was unsuccessful); biochemically verified exhaled carbon monoxide. RA disease activity score (DAS28CRP) : a composite measure of patient global score, tender and swollen joint counts and C-reactive protein, at 6, 12, 18 and 24 months. DAS-remission will be defined as a DAS < 2.4. Remission duration will be defined as the length of time over which a DAS < 2.4 is measured. Cardiovascular disease risk: will be measured using the Australian CVD Risk Calculator (31), which calculates CVD risk percentiles based on input variables. Overall health-related quality of life: Assessment of Quality-of-Life score 8 Dimension (AQoL-8D) score We will evaluate the 5 components of Reach, Effectiveness, Adoption, Implementation, Maintenance from the (RE-AIM) framework in the RA-HEAL study. R each refers to eligible people willing to engage with programs. It will be measured firstly as the number of people who consent to the trial as a function of the number of queries from eligible potential participants. Participant representativeness will compare sociodemographic, lifestyle and clinical profile of the trial participants with the A3BC database of RA participants with RA onset in the last 12 months. Reach in each arm will be assessed as the proportion of participants recruited to the study who (i) in program A engage with each component (resilience, exercise training, nutrition, smoking cessation, and behaviour change) and (ii) in program B seek engagement with professional services related to mental health, exercise, nutrition or smoking cessation support for RA, including through The Arthritis Movement programs or private service providers. E ffectiveness refers to short-term impact. It will be measured as the change from baseline at 6, 12, 18 and 24 months using the measures specified in the primary and secondary outcome measures. A doption refers to an agency’s use of an intervention. It will be measured as: Number and characteristics of staff implementing the program. I mplementation refers to the delivery of the intervention. It will be measured as: Fidelity : An online checklist from multidisciplinary interventionists will be used to assess the consistency of Program A delivery (e.g. number of sessions provided, content covered) against written protocols. Provision of written information resources to participants will be recorded. Feasibility: The proportion of participants completing each component of and the entire program A relative to the number allocated to and commencing program A, and The proportion of participants engaging with Program A sessions as a function of the total number of sessions for each of the program A components. Acceptability: Participant feedback on satisfaction with and perceived helpfulness of their program and resources for RA self-management. Program A intervention experiences, and associated barriers and enablers to engagement across the various component sessions. Cost effectiveness : Modified cost diaries capturing health resources accessed, supplemented by Medicare Benefit Schedule (MBS) and Pharmaceutical Benefit Scheme (PBS) data. Health resources will be valued using market prices and industrial wages. Utility scores to allow quality-adjusted life years (QALYs) gained will be obtained using SF-6Dv2, a subset of SF36v2 using Australian weights. An exploratory analysis will compare the performance of SF-6Dv2 and AQoL-8D . M aintenance refers to sustained change and will compare the primary and secondary effectiveness measures at 6, 12, 18 and 24 months. Schedule of enrolment, interventions, and assessments (SPIRIT Figure) Participant timeline {13} On-study Exit Evaluation Assessment Screening ᵃ Month 1 Baseline Month 6 Month 12 Month 18 Month 24 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Visit 6 1 Eligibility Assessment/ Confirmation X 2 Informed consent X 3 Initial Participant screening survey X 4 Physical Examination (symptom directed) X X X X X 5 Vital Signs/Body Weight/Height X X X X X 6 SOC RA bloods: (FBP, ESR, CRP, ELFT, Lipid profile) X X X X X 7 RF anti-CCP X 8 A3BC blood sampling and oral swab (PBMC, DNA, serum processing and store) for exploratory immune and biomarker assays X X X X X 9 A3BC stool sampling for microbiome and metabolomics X X X X X 10 ECG X 11 Physical function scores (6MWT, TUG, grip strength, 5XSST, 30 sec arm curl, single leg balance, 4m gait speed test) X X X X X 12 Application of Actigraph monitor (7 days) X X (week 20) 13 Exhaled CO2 (Smokers only) X X X X X 14 Adverse Event X X X X 15 Randomisation Xᵇ RA-HEAL-A3BC Questionnaireͨ 16 Medical History (symptom directed, CVD) X X Xͩ Xͩ Xͩ Xͩ 17 Concurrent Medications X X X X X X 18 Disease activity score (SJC, TJC, VAS, RADAI, RAPID3) X X X X X 19 Employment Status, Financial benefits X X X X X 20 Diet quality (MediCul) X X X X X 21 Cost utility (SF36v2, AQoL-8D) X X X X X 22 Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) X X X X X 23 Perceived Stress Scale X X X X X 24 Perceived Competence X X X X X 25 Professional Assistance X X X X X 26 National Health Survey (exercise) X X X X X 27 Social Support Questionnaire X X X X X 28 Equity Scale X X X X X 29 Feedback survey (all participants) – additional services/resources accessed and satisfaction X X X X 30 Feedback survey program A X 31 Focus group session X Footnotes: ᵃ Screening Visit is completed via telehealth/online ᵇ Participants will be randomised before their Baseline Visit onsite once verbal consent is obtained at their Screening visit (telehealth/online). ͨ RA-HEAL A3BC questionnaire can be completed online before the in-person assessments at Baseline, Month 6, 12, 18, and 24 or in-person during their in-person visits at the same timepoints. ͩ Only collecting significant change to participant’s medical history. Sample size {14} Sample sizes of 62 participants for each of Program A and B were estimated based on pilot program physical health-related QoL SF36 data (32), to achieve 80% power to detect a superiority margin of 40% improvement using a one-sided, two-sample t-test. The true difference between the means is assumed to be 26.39 and standard deviation assumed to be 20.53. The significance level (alpha) of the test is 0.025 (as one sided). With a 20% dropout rate based on the pilot intervention and among local patients with new-onset RA recruited to the A3BC cohort study, 78 participants are needed per arm (156 in total). Assignment of interventions: allocation Sequence generation {16a} Participants will be block randomized in blocks of 4, stratified for current smoking history to ensure similar representation in each arm, and allocated 1:1 to Program A or Program B, according to a computer-generated randomization table. Concealment mechanism {16b} Participants will be randomised according to a computer-generated randomization table held centrally by the senior statistician and data manager (concealed group allocation) then informed as to their group, along with options for group sessions for Program A participants, by the unblinded trial administrative officer. Assignment of interventions: Blinding Who will be blinded {17a} After randomisation, the administrative officer, participants and interventionists will be aware of Program allocation. In order to minimize bias the PI, outcome assessors, laboratory personnel and statistical personnel will be blinded as to allocation of individual participants. Data collection and management Plans for assessment and collection of outcomes {18a} Assessments (Figure 3) conducted at baseline, 6, 12, 18 and 24 months, and carried out by the PI and outcome assessors will be in-person at the Clinical Research Facility, Princess Alexandra Hospital. Questionnaires will collect: Basic demographics including age, gender, duration of RA, financial benefit status Health related Quality of Life, physical (SF36 v2) Health related Quality of Life (AQo-8D) Medication RA disease activity indices Employment status, including work productivity/activity impairment Physical activity/sitting time – National Health Survey Diet quality – MediCul Index Mental health (SF36 v2), Mental Wellbeing Scale, Perceived Stress Scale) Confidence for Self-Management of Arthritis Scale Use of professional services/assistance for mental health, exercise, nutrition, smoking cessation engagement Cigarettes smoked/nicotine dependence/quitting self-efficacy Program A participant attendance records, adverse events, adherence to nicotine replacement products, and exercises completed will be monitored by the interventionists. Program A participants will be invited to participate in a focus group discussion to provide additional feedback at Month 6. Plans to promote participant retention and complete follow-up {18b} The intervention is patient-centred and will offer options for different locations for on-site visits, and for some sessions to be delivered via videoconference. Investigators will make every reasonable effort to keep each participant in the study unless there is a safety concern with continuing. After 2 consecutive non-attendances, participants will be contacted by Short Message Service (SMS). Participants will continue to be offered the opportunity to attend assessments unless they advise they wish to withdraw from the trial. If an adverse event is the reason for a participant’s withdrawal the investigator will encourage the participant to be followed up for the full study period and complete the exit evaluation at 24 months post intervention. If a participant withdraws from RA-HEAL, separate withdrawal from A3BC will be discussed. Data management {19} Study survey data are captured electronically into the secure web application REDCap. The surveys will be completed at each in-person study visit. The study monitor will review data on a regular ongoing basis and for clarification and correction (where applicable) until database lock. Confidentiality {27} Participants will be allocated unique RA-HEAL and A3BC participant identification numbers (IDs). Only participating clinicians and project staff will be directly aware of participant identities. All data will be stored in a re-identifiable format for participant tracking and follow-up. These IDs will be used on all documentation and biological samples. Any researcher access to participant data will be in a non-individually identifiable format. No patient information will be released carrying personal identifiers unless pertinent to care (see below). Results of research analyses will not be fed back individually to participants, but aggregate reports may be published in peer-reviewed journals, and/or presented to appropriate audiences. It will not be possible to re-identify individuals from such reports. Linked administrative health data will be accessible where participants have authorised this on the A3BC consent form. Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data for the cost-utility analysis may be linked via Services Australia or the Australian Institute of Health and Welfare (AIHW). Linked data will be stored and/or accessed in accordance with the A3BC’s data linkage ethics approvals and applicable data custodian requirements. Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33} Biological samples stored with linked clinical data at baseline, 6-, 12-, 18- and 24-months include Peripheral Blood Mononuclear Cells (PBMC), serum, plasma, stabilised whole blood RNA, DNA (baseline) and stool. Planned laboratory evaluations include immune cell populations (including autoantigen-specific T cells) by flow cytometry, serum/plasma soluble analytes, stool and serum metabolomics including short chain fatty acids and lipidomics. All analyzed data will be uploaded to the A3BC database . Statistical methods Statistical methods for primary and secondary outcomes {20a} Before modelling trial outcomes, baseline demographic, lifestyle and clinical characteristics of Program A and Program B participants will be compared to establish whether randomization succeeded in creating comparable groups. Any characteristics not comparable at baseline will be modelled as covariates in subsequent analyses to adjust for possible confounding effects. Outcomes will be assessed using linear mixed modelling (LMM) and will be used to evaluate effectiveness of the intervention on the primary and secondary outcomes, which are continuous. LMM will examine whether changes in the outcomes of interest vary over time as well as across the two groups, after adjusting for the effects of any potential confounders. This approach is chosen due to its robustness in handling unbalanced data and its ability to model both the fixed effects of intervention and time, as well as random effects that account for inter-subject variability. Intervention effects will be assessed post-intervention (6 months) and during the maintenance period (12, 18 and 24 months). Model fit will be assessed using the Aikake and Bayesian Information Criteria, and diagnostic plots will check for deviations from model assumptions. An economic evaluation form from the health care system perspective will be conducted to determine the incremental cost per additional quality adjusted life year (QALY) gained for Program A over Program B and will include deterministic linked MBS and PBS data. Nonparametric bootstrapping will used to characterize the uncertainty in the economic evaluation results. Interim analyses {21b} The primary outcome and 6-month secondary outcomes will be determined once all participants have completed 6-month assessment. Data collection will continue 6-monthly until the 2-year visit, at which time the extended longitudinal outcomes will be determined. A value-of-information analysis will be conducted as an extension to the economic evaluation to assess whether the evidence is sufficient to inform decision-making for implementation or if more data should be collected. Methods for additional analyses (e.g. subgroup analyses) {20b} Participants who smoke, who were purposively sampled and balanced between intervention groups and who receive specific intervention will be analyzed together with all participants, and as a separate subgroup. To identify any other relevant subgroups, at the primary endpoint, key clinical and demographic data will be clustered using an unbiased approach to determine variables, other than the intervention, contributing to the primary outcome using outcome-guided clustering. This will build a random survival forest and compute the distances between all observations based on the fitted model. Based on the distances, hierarchical clustering identifies clusters of samples with similar characteristics and survival rate. Further subgroup analysis will be based on the outcome of the clustering. Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c} The basis of statistical analysis will be intention-to-treat for those participants attending at least 25% of the sessions from all components. Missing values will be examined for their patterns and distributions, and multiple imputation will be used if all relevant assumptions are met. Plans to give access to the full protocol, participant level data and statistical code {31c} Full protocol, participant level data, and statistical code will be accessible after trial completion upon request per the A3BC Access Policy. New analyses must be reviewed and approved by a human research ethics committee, the A3BC Consortium Committee and Access Committee prior to release of samples and/or data. Oversight and monitoring Composition of the coordinating center and trial steering committee {5d} The coordinating centre at the University of Queensland comprises a clinical nurse coordinator, administrative officer, PI, sub-PI and clinical research assistant. The REDCap data management platform, A3BC data manager and biobank manager are located at the University of Sydney. The A3BC steering/consortium committee comprises clinical leads from each state in Australia, including the RA-HEAL lead investigator, Ranjeny Thomas in Queensland. The Trial Steering Committee comprises the PI and sub-PI and lead CHP, DN, EP and smoking interventionalists. Composition of the data monitoring committee, its role and reporting structure {21a} The data monitoring committee comprises the data monitor and A3BC data manager. They report to the Trial Steering Committee and are independent of the sponsor. They are governed by a data monitoring charter. Adverse event reporting and harms {22} The procedure for reporting AEs is provided with the Participant Information Sheet along with a central study email address and the contact details of local research team members. Participants are encouraged to record any adverse events (AEs e.g. injury) or serious adverse event (SAEs) to a member of the research team (e.g. the relevant interventionist/s or project coordinator). All participants are also provided with a diary to record AEs/SAEs. The coordinator will keep a record of all reported AEs. Participants will be referred to their general practitioner or rheumatologist should they need further management. AEs include any occurrences that are new in onset or aggravated in severity or frequency from the baseline condition, or abnormal results, including laboratory test abnormalities. Pre-existing conditions or diseases that occur during the study (e.g., arrhythmias, rheumatoid arthritis) will not be considered as AEs unless they change in frequency or severity. Elective surgery or other scheduled hospitalisation periods that were planned before the participant was included in this trial are not to be recorded as SAEs, unless an outcome is considered serious. SAEs will be reported to the approving Human Research Ethics Committee within 15 calendar days of the sponsor becoming aware of the issue. All SAE documents are stored in the participant’s study record and are retained as per the Study Record Retention policy. Frequency and plans for auditing trial conduct {23} There are no plans for independent auditing, but the trial may be audited at random by the Human Research Ethics Committee. Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25} Participants will be informed by email of any relevant protocol amendments approved by the Human Research Ethics Committee. Dissemination plans {31a} Participants will receive a written lay summary of the main outcomes of the trial in an email newsletter and will be invited to community-based presentations on the trial aims and outcomes. Trial outcomes will be published in scientific literature and doctoral theses, presented to clinical and academic audiences at conferences and seminars, and reports formatted for consumption by lay audiences and policy makers. Discussion RA-HEAL tests whether a tailored intervention including formal resilience training with a clinical psychologist followed by exercise, nutrition counselling, smoking cessation and behavior change support has a greater effect on health-related QoL than written advice given in current best-practice settings. RA management recommendations reinforce the importance of early diagnosis and early treatment to a target of remission, in order to minimise inflammation, reduce risk of long-term complications and maximise QoL (33, 34). A unique feature of RA-HEAL is that it targets RA within 12 months of onset. Diagnosis provides a strong opportunity for physician-patient interaction (“teachable moment”) to initiate steps towards behavior change (35). Furthermore, although long-term adherence to lifestyle changes is critical for prolonged benefits to microbiome, cardiovascular and immune health, most existing trials of lifestyle intervention have relatively short duration of follow-up. RA-HEAL’s linkage with A3BC provides the framework to support not only the 6 monthly follow-up data and biological sampling to 24 months post-intervention for RA-HEAL Trial, but the opportunity for further annual surveys beyond 24 months with A3BC, creating a valuable resource for future research. Thus, in its secondary outcomes, RA-HEAL will assess the longevity of effects of intervention or best-practice usual care for up to 2 years, with the option for ongoing, longer-term surveys and data linkages through A3BC Depression in RA is associated with poorer disease outcomes (36) and the rates of depression and anxiety are higher in patients with RA than controls, attributable to pain, fatigue, functional limitation, reduced capacity for work and reduced ability to participate in valued activities. Patients with low self-management behaviour also have higher risks of anxiety and depression (37). Whilst other multidisciplinary RCTs such as the PFJ and MADEIRA trials have provided general psychoeducation on stress and relaxation training (7, 9), the RA-HEAL resilience component extends this further by offering a more structured patient-centred resilience training based on principles of CBT and ACT which are consistently recognised as evidence-based psychological treatments (38). Patient activation for self-management is the focus of the resilience training offered at the start of the RA-HEAL intervention and will be specifically assessed with a confidence for self-management scale. Chronic inflammation induced by gut dysbiosis and the negative impacts of inactivity have been implicated as potential causal factors in the development and progression of RA (39, 40). The Mediterranean diet consists of higher consumption of fibre-rich plant-based-foods such as fruits, vegetables, legumes, nuts and whole grains, more moderate consumption of fish, poultry and dairy, and low consumption of red meat. It has been proposed as an intervention to modify intestinal microbiota and mitigate dysbiosis in the management of RA (41). Physical activity benefits people with RA in terms of joint function and mobility but also mood and fatigue. It may benefit associated comorbid conditions such as cardiovascular disease, as well as overall QoL (42). Physical activity may reduce disease activity and inflammation and improve symptoms, providing an effective tool in the management of RA (43). These outcomes support the recommendation of Mediterranean diet principles and exercise in both arms of RA-HEAL. Composite end-points such as health-related QoL are highly valued by patients with RA, as they incorporate a broad range of health outcomes, not only including pain and joint damage, but also their capability for activities of daily living, mobility, life enjoyment, independence, management of fatigue and participation in valued activities (44). Health-related QoL, as assessed by the SF-36v2 scale (45), is sensitive to adverse disease impacts in multiple domains, and thus is a useful primary-outcome target for assessing interventions (46). The physical-component score primary outcome measure was particularly sensitive to change in the pilot intervention, in keeping with improvements in physical function (15). As data are linked to multiple state and federal health data collections for those participants who elect to maintain their A3BC consent after completion of RA-HEAL, there will be opportunities to validate self-report of health-related events and medications, to determine medium and long-term effects of behavior change and to strengthen cost-utility analyses. The goal of effective lifestyle intervention is to reduce the burden of RA in individuals that includes distress, reduced function, disability, medical and allied health consultations, medications, surgery, and long-term complications, and the public-health burden of RA to the community. The outcomes of our comprehensive comparison of intervention and best practice usual-care programs in the RA-HEAL trial should provide evidence for a scalable approach to deliver, engage and sustain people with newly diagnosed RA in self-management. This may have implications for service delivery and specific health service roles. Implementing effective models of management over the long term would result in substantial cost savings for the healthcare system. Abbreviations Administrative information Introduction Title Katherine A Poulsen, Nicola W Burton, Hannah L Mayr, Veronique S Chachay, Jeff S Coombes, Coral E Gartner, Amee Sonigra, Paul Christensen, Karl Hansford, Dianna J Ang, Jessica Neri, Ramali Mendis, Tom Lynch, Cheryl Dines, Helen Benham, Aoife Sweeney, Lyn M March, Asaduzzaman Khan, Haitham Tuffaha and Ranjeny Thomas. Maintenance refers to sustained change and will compare the primary and secondary effectiveness measures at 6, 12, 18 and 24 months. The protocol and Participant Informed Consent Form were approved by the Metro South Human Research Ethics Committee. Not applicable The authors declare no competing interests Funding Funded by Medical Research Future Fund (MRFF) Grant ID:2032246 The funding body played no role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript. Authors’ contributions Concept, study and instrument design: RT, NB, JC, HM, VC, CG, KP, AoS, JN, HB, CD, LM, KH, DA, RM, TL, PC. Statistical design: AK. Health Economic Evaluation design: HT. Drafted manuscript: KP, RT. Obtained funding: RT. Edited manuscript: all authors. Trial status Protocol version: 1.3, dated March 12, 2025 Recruitment commencement: March 12, 2025 Approximate recruitment completion: July 01, 2026 Abbreviations Trial status Protocol version: 1.3, dated March 12, 2025 Recruitment commencement: March 12, 2025 Approximate recruitment completion: July 01, 2026 Declarations Ethics approval and consent to participate {24} The protocol and Participant Informed Consent Form were approved by the Metro South Human Research Ethics Committee. Consent for publication {32} Not applicable Availability of Data and Materials {29} All trial investigators will have access to the final dataset, as agreed in the Multi-Institutional Agreement and Clinical Trial Research Agreement. Competing Interests {28} The authors declare no competing interests Funding Funded by Medical Research Future Fund (MRFF) Grant ID:2032246 The funding body played no role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript. 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Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, EQ-5D [corrected] RAQoL, and HAQ in patients with rheumatoid arthritis. J Rheumatol. 2008;35(8):1528-37. Matcham F, Scott IC, Rayner L, Hotopf M, Kingsley GH, Norton S, et al. The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;44(2):123-30. Supplementary Files SPIRITChecklistdownload8Jan13.pdf Cite Share Download PDF Status: Published Journal Publication published 29 Sep, 2025 Read the published version in Trials → Version 1 posted Reviewers agreed at journal 11 Jul, 2025 Reviewers invited by journal 11 Jul, 2025 Editor assigned by journal 10 Jun, 2025 First submitted to journal 09 Jun, 2025 Editorial decision: Minor revision 04 Jun, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6552255","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484129178,"identity":"041b590f-0e94-419f-821f-7e1ceb5d6e16","order_by":0,"name":"Katherine Poulsen","email":"","orcid":"","institution":"The University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Katherine","middleName":"","lastName":"Poulsen","suffix":""},{"id":484129179,"identity":"fb3665e7-f45d-4402-b718-2ec1ed1c0381","order_by":1,"name":"Nicola Burton","email":"","orcid":"","institution":"Griffith University","correspondingAuthor":false,"prefix":"","firstName":"Nicola","middleName":"","lastName":"Burton","suffix":""},{"id":484129180,"identity":"e3fd047b-eb13-45ea-b2cb-92953a5382f3","order_by":2,"name":"Hannah Mayr","email":"","orcid":"","institution":"Princess Alexandra Hospital Health Service District: Princess Alexandra Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Mayr","suffix":""},{"id":484129181,"identity":"70f40af6-4fef-4e0a-80ca-e706313720ca","order_by":3,"name":"Veronique Chachay","email":"","orcid":"","institution":"The University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Veronique","middleName":"","lastName":"Chachay","suffix":""},{"id":484129182,"identity":"a46365a6-8e40-4c20-80cd-280be0cc3465","order_by":4,"name":"Jeff Coombes","email":"","orcid":"","institution":"The University of 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2","display":"","copyAsset":false,"role":"figure","size":56171,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIntervention schedule\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6552255/v1/a41dd1c73424683bb34d00b1.png"},{"id":87242768,"identity":"b789f437-d673-4e14-9179-c0ec1a31ab07","added_by":"auto","created_at":"2025-07-22 01:51:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":95951,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssessments and outcomes collected\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6552255/v1/94ecce3bda0dbc83e51238ca.png"},{"id":92883703,"identity":"036ca7dd-ec2b-4e74-a583-2004b79b3ca2","added_by":"auto","created_at":"2025-10-06 16:08:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2063032,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6552255/v1/50c7f9a2-4925-4495-b759-15d850aafe21.pdf"},{"id":87242769,"identity":"06cc4f9d-8bdd-41f2-a556-848281b3425e","added_by":"auto","created_at":"2025-07-22 01:51:33","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":125159,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRITChecklistdownload8Jan13.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6552255/v1/d04de380021f20b00cb4a6a7.pdf"}],"financialInterests":"","formattedTitle":"Resilience And Healthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomised, parallel group, placebo-controlled clinical trial protocol","fulltext":[{"header":"Administrative information","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"639\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eTitle {1}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003e\u003cu\u003eR\u003c/u\u003eesilience \u003cu\u003eA\u003c/u\u003end \u003cu\u003eHea\u003c/u\u003elthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomized, parallel group, placebo-controled clinical trial protocol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eTrial registration {2a and 2b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eACTRN12625000050459, ANZCTR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eProtocol version {3}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003e1.3, 12 March 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eFunding {4}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eMedical Research Future Funder (MRFF) Clinician Researchers - Applied Research in Health ID: 2032246\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAuthor details {5a}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eKatherine A Poulsen, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, The Prince Charles Hospital, Chermside QLD 4032 Australia, The Royal Brisbane and Women\u0026rsquo;s Hospital QLD 4029\u003c/p\u003e\n \u003cp\u003eNicola W Burton, School of Applied Psychology, Griffith University, Brisbane, QLD 4111 Australia\u003c/p\u003e\n \u003cp\u003eHannah L Mayr, Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia; and Faculty of Health Medicine and Behavioural Sciences, University of Queensland, Brisbane, QLD 4072 Australia\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVeronique Chachay, Frazer Institute, The University of Queensland, Woollongabba, QLD 4102 Australia.\u003c/p\u003e\n \u003cp\u003eJeff Coombes, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4072 Australia.\u003c/p\u003e\n \u003cp\u003eAmee Sonigra, Department of Rheumatology, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePaul Christensen, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102,\u003c/p\u003e\n \u003cp\u003eKarl Hansford, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102,\u003c/p\u003e\n \u003cp\u003eDianna J Ang, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102,\u003c/p\u003e\n \u003cp\u003eJessica Neri, The Arthritis Movement, PO Box 2121, Lutwyche, QLD, 4030\u003c/p\u003e\n \u003cp\u003eRamali Mendis, Department of Rheumatology, Princess Alexandra Hospital, Brisbane, QLD 4102 Australia,\u003c/p\u003e\n \u003cp\u003eTom Lynch, Institute of Bone and Joint Research, The Australian Arthritis and Autoimmune Biobank Collaborative, Kolling Institute, The University of Sydney, St Leonards NSW 2065, Australia,\u003c/p\u003e\n \u003cp\u003eCheryl Dines, The Arthritis Movement, PO Box 2121, Lutwyche, QLD, 4030\u003c/p\u003e\n \u003cp\u003eHelen Benham, The University of Queensland Faculty of Health, Medicine and Behavioural Sciences and Princess Alexandra Hospital Woolloongabba, QLD 4102, Australia\u003c/p\u003e\n \u003cp\u003eAoife Sweeney, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102,\u003c/p\u003e\n \u003cp\u003eLyn M March, Institute of Bone and Joint Research, The Australian Arthritis and Autoimmune Biobank Collaborative, Kolling Institute, The University of Sydney, St Leonards NSW 2065, Australia,\u003c/p\u003e\n \u003cp\u003eAsaduzzaman Khan, School of Health and Rehabilitation Sciences\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe University of Queensland, Brisbane QLD 4072 Australia\u003c/p\u003e\n \u003cp\u003eHaitham Tuffaha, Centre for the Business and Economics of Health, The University of Queensland, Brisbane QLD 4072 Australia\u003c/p\u003e\n \u003cp\u003eRanjeny Thomas, Frazer Institute, The University of Queensland, Wolloongabba QLD 4102, Australia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eName and contact information for the trial sponsor {5b}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eThe University of Queensland\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAssociate Director, Research Commercial Management\u003c/p\u003e\n \u003cp\u003eBrisbane, QLD 4072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eRole of sponsor {5c}\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 421px;\"\u003e\n \u003cp\u003eSponsor provides all information about the intervention to the Principal Investigator (PI) to conduct the study;\u003c/p\u003e\n \u003cp\u003ePrepares and submits all required documentation to obtain study approval and initiation;\u003c/p\u003e\n \u003cp\u003eImplement and maintains quality assurance and quality control systems for conduct and data generation in the study;\u003c/p\u003e\n \u003cp\u003eRegisters the study on the appropriate clinical trials registry;\u003c/p\u003e\n \u003cp\u003eDesignates appropriately qualified personnel to advise on study-related medical questions or problems;\u003c/p\u003e\n \u003cp\u003eNotifies the HREC of trial cessation or any adverse events.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Introduction","content":"\u003cp\u003e\u003cstrong\u003eBackground and rationale {6a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRheumatoid arthritis (RA) is a chronic, inflammatory autoimmune arthritis. In Australia, it affects up to 1.5% of people and is estimated to account for 16% of the total burden of disease for all musculoskeletal conditions, with an estimated $966.1 million spent on its management (1, 2). Etiology involves genetic and environmental risks, with an estimated population-attributable risk of potentially-modifiable health factors of 40% (3). The importance of personalized health care and multidisciplinary programs to support self-management of rheumatoid arthritis (RA) is increasingly recognized. These are empowering for patients, improving both physical and mental health. Multi-disciplinary programs t for self-management can be presented in a variety of ways including individual, group and online platforms. Despite international consensus on the importance of this as standard of care, inadequate support for self-management, particularly access to multidisciplinary care, is a common issue across many health services (1, 4). In Australia, access to multidisciplinary teams varies across hospitals and health services. In the community, general practitioners coordinate health care plans for patients with eligible chronic health conditions which allows for just five Medicare rebates per calendar year across all allied health services. Using the Medicare rebate, many service providers still charge gap payments which may present financial barriers (5). Besides these barriers, in some services such as psychology, demand for services may far outstrip supply (6). In combination, these factors can present barriers to access for patients.\u003c/p\u003e\n\u003cp\u003eSeveral small randomized controlled trials (RCT) have assessed the impact of multidisciplinary interventions in people with RA.\u0026nbsp;The ‘Plants for Joints’ RCT (n=83) enrolled patients with longstanding RA and low-moderate disease activity into a 16-week lifestyle program which incorporated a whole-food plant-based diet, physical activity and stress management. This study commenced with a dietary and physical activity component, which was followed by a stress-management component consisting of psychoeducation on the effects of stress on health, stress management and guided exercises on breathing, visualisation and relaxation techniques supported by podcasts and videos (7, 8).\u0026nbsp;The intervention led to greater improvements in body weight, glucose control, low density lipoprotein and Disease Activity Score (DAS28) than the usual care group over 16 weeks.\u0026nbsp;The\u0026nbsp;Mediterranean DiEt In Rheumatoid Arthritis (MADEIRA)\u0026nbsp;RCT (n=40) included personalised dietary planning based on the Mediterranean diet, cooking tips and demonstration, and \u0026nbsp;group discussion on physical activity, stress management, relaxation and sleep hygiene in a 12-week intervention in women with RA \u0026gt;2 years duration and found improved DAS28 and reduction in Body Mass Index (BMI) post-intervention. The personalized Mediterranean diet plan and advice on physical activity was supported through nudges by a computer-based clinical decision support systems platform(9). Another RCT demonstrated that the Mediterranean diet combined with exercise improved health-related quality of life (QoL) and functional ability in women with longstanding RA of many years’ duration, compared to control or Mediterranean diet alone\u0026nbsp;(10, 11).\u0026nbsp;In a systematic review, Mediterranean diet had beneficial effects in people with RA across inflammation, disease activity and CVD risk profile\u0026nbsp;(12). A small RCT (n=51) comparing the Mediterranean diet to Western diet in patients with RA of \u0026gt;2 years duration demonstrated improvement in \u0026nbsp;health related QoL (SF-36 vitality score) and DAS28 score over a 12 week intervention period\u0026nbsp;(13). Another controlled, non-randomised study (n=130) of a 6-week Mediterranean diet intervention in women with longstanding RA identified improved pain scores, patient global and function but not DAS28 in the intervention group\u0026nbsp;(14).\u0026nbsp;No RCT has assessed the effects of a multidisciplinary intervention that combines dietary, exercise, smoking cessation, psychological and behavior change support components. Furthermore, there is a need to explore these approaches in newly diagnosed RA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Resilience and Healthy Lifestyle for Rheumatoid Arthritis (RA-HEAL) Trial is a pragmatic RCT that aims to compare a structured multidisciplinary lifestyle intervention with self-directed activities in best-practice usual care. The structured intervention in RA-HEAL is designed to provide participants with an integrated multi-disciplinary approach to promote health self-efficacy, to enhance resilience, implement medical management and reduce the need to coordinate multiple practitioners to assist with wellbeing and lifestyle changes in smoking, exercise and diet quality. In a pilot intervention we found that the 4-month multidisciplinary resilience followed by healthy lifestyle (diet, exercise, behavior change support) program enhanced the confidence and capability of people with longstanding RA to self-manage RA, with benefits in wellbeing, diet quality, physical function, DAS28, BMI and Quality of Life (QoL)(15). Unlike previous studies, this trial is targeting people with early RA, who have received a diagnosis within the past 12 months, since the early stages of RA represent a window of opportunity for downregulation of inflammation, and the potential to change disease trajectory in the long term (16).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives {\u003c/strong\u003e\u003cstrong\u003e7}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe aim of this trial is to assess the feasibility, effectiveness, acceptability and durability of a structured, multidisciplinary, multicomponent resilience and healthy lifestyle (smoking cessation, nutrition, exercise) intervention to improve health self-efficacy and QoL among people with early RA.\u003c/p\u003e\n\u003cp\u003eOur primary objective is to determine whether RA-HEAL intervention improves health-related QoL relative to usual best practice care at 6 months post intervention. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecondary objectives include whether, relative to best practice usual care, and at 6-24 months post intervention, RA-HEAL intervention:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eIs feasible, acceptable and safe for participants\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eImproves mental health, physical activity and function, diet quality, and (where indicated) smoking cessation/confidence, as well as overall health related QoL up to 24 months.\u003c/li\u003e\n \u003cli\u003eImproves participant efficacy for RA self-management\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eIncreases likelihood of attaining and maintaining DAS28-remission in the first 2 years after diagnosis\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRepresents value for money \u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eOur primary hypothesis is that RA-HEAL intervention improves health-related QoL relative to best practice usual care at 6 months post-intervention, as determined by the physical health component score within the standardized QoL questionnaire, 36-item Short Form Survey version 2 (SF-36 v2).\u003c/p\u003e\n\u003cp\u003eOur secondary hypotheses are that at 6-24 months post-intervention, relative to best practice usual care, that RA-HEAL intervention improves:\u0026nbsp;\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eParticipant efficacy for self-management\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMuscular fitness and exercise capacity\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDiet quality\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDuration of smoking cessation\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRA disease activity\u003c/li\u003e\n \u003cli\u003eDuration of RA remission\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCardiovascular disease risk profile\u003c/li\u003e\n \u003cli\u003eMental health \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOverall health related quality of life\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eTrial design {8}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRA-HEAL is an open-label pragmatic randomised controlled trial. The trial has been designed to compare a structured, multidisciplinary, multicomponent resilience and healthy lifestyle program (Program A) with the provision of multicomponent written lifestyle advice as part of best practice usual care (Program B) in people with early RA. Both programs focus on subjective wellbeing and a healthy lifestyle, including exercise, healthy eating and (if indicated) smoking cessation (Figure 1). Eligible participants will be randomly allocated to Program A or Program B. RA-HEAL will recruit people with early RA who are willing and motivated to commit to a 20-week multi-modal intervention with the potential for regular online and face-to-face interventions with a multidisciplinary team. Participants must also be willing to be enrolled in the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), a national musculoskeletal and autoimmune disease biobanking network that facilitates the sharing and storage of data and biospecimens for ethics-approved, open-access research into arthritis and autoimmune conditions (17, 18).Data and biospecimens for this trial will be managed using the A3BC platform.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods: Participants, interventions and outcomes","content":"\u003cp\u003e\u003cstrong\u003eStudy setting {\u003c/strong\u003e\u003cstrong\u003e9}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRA-HEAL will be undertaken in the greater Brisbane metropolitan area of Australia, centered on the City of Brisbane and including the Ipswich and Logan areas of Greater Brisbane. \u0026nbsp;Eligible participants will remain under the care of their usual treating rheumatologist and usual general practitioner (GP). The interventions for Program A participants will be offered at 4 study locations within Greater Brisbane.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility criteria {10}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion criteria\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eAdults with RA who are at least 18 years old.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRA onset in the last 12 months, diagnosed according to ACR/EULAR 2010 Classification Criteria (19), managed by a rheumatologist with conventional or biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eResiding in Greater Brisbane Area, including Ipswich and Logan\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWilling and able to access and participate in individual and group program sessions (in-person and online) as an adjunct to continuing their RA treatment\u0026nbsp;with their usual rheumatologist.\u003c/li\u003e\n \u003cli\u003eAmbulatory and cleared for participation in an exercise program by a medical practitioner.\u003c/li\u003e\n \u003cli\u003eWilling to be concurrently enrolled in A3BC. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAble to speak and understand English at a level capable of understanding the informed consent process as determined by the principal investigator.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eExclusion\u0026nbsp;criteria\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eMedical conditions contraindicated to exercise training (e.g. unstable angina) \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCurrent or intended attendance in a program promoting RA self-management \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCurrently receiving psychiatric, psychological or counselling treatment\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSignificant lower limb musculoskeletal impairment preventing stationary cycling\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eWho will take informed consent? {26a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter initial contact with potential participants, the research team will use the approved recruitment script to facilitate conversations. Prospective participants will attend a telehealth/online screening visit with the PI (or delegated staff member). For those participants providing verbal consent, the consent process will be clearly documented in the patient\u0026rsquo;s medical record as per standard practice.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional consent provisions for collection and use of participant data and biological specimens {26b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent will be completed in person at the RA-HEAL-A3BC baseline visit at the Princess Alexandra Hospital Clinical Research Facility. Participants not previously enrolled in A3BC will be required to first sign the A3BC consent form. Consent to A3BC includes permission to collect and biobank biological samples (blood, oral swab and faeces). After consent to the RA-HEAL trial, which includes access to usual care routine blood work, a letter will be sent from the PI to the participant\u0026rsquo;s treating rheumatologist and general practitioner advising them of their patient\u0026rsquo;s participation in RA-HEAL and requesting access to rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), as well as lipid profile and C-Reactive Protein (CRP) concomitant with each visit.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment {15}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be recruited via information and promotional notices provided through rheumatologists, consumer support organizations such as The Arthritis Movement\u0026nbsp;(20) and various media. Coordinators will also invite RA HEAL-eligible participants already enrolled in A3BC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWithdrawal\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants can withdraw from RA-HEAL at any time without having to give a reason. If participants choose to withdraw they will be provided with a withdrawal form to sign. If a participant withdraws from RA-HEAL, separate withdrawal from A3BC will be discussed. Under such circumstances, they may optionally stop actively participating but allow for their samples and data already in the biobank to continue to be used in research, or disallow further use of their samples, and request that their samples and data are destroyed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExplanation for the choice of comparators {6b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth the European League of Rheumatology EULAR and the American College of Rheumatology (ACR) recommend that patients with rheumatic diseases are educated about the benefits of managing stress and lifestyle improvements including a healthy diet, regular exercise and encouragement to quit smoking (21, 22). The comparator group will receive usual best practice care, which incorporates the provision of advice on recommended lifestyle modifications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention description {11a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTUDY ARMS: all participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the baseline assessment, all participants\u0026nbsp;will receive written lifestyle advice information sheets from Arthritis Australia (Arthritis and Emotional Wellbeing; Exercise and RA; Healthy Eating and Arthritis; Physical Activity Arthritis Information Sheet; 10 Steps For Living Well With Arthritis) (23), as well as from the Australian Rheumatology Association (ARA) (Things You Can Do to Manage Your Rheumatoid Arthritis (24));\u0026nbsp;The Quitline for smoking cessation, and\u0026nbsp;The Arthritis Movement contact details for support and exercise programs\u0026nbsp;(20), with questions answered verbally by the PI. All participants will receive a diary in which to record adverse events, such as injuries.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTUDY ARMS: PROGRAM A: RA-HEAL INTERVENTION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgram A participants will take part in the RA-HEAL intervention. It will be delivered over 5 months, comprising five partially overlapping multidisciplinary person-centered interventions designed to recognize individual preferences, values, and concerns; with shared decision making, empowerment, and physical and emotional support, with some basic resources provided.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProgram A will be delivered as a combination of one-on-one or group in-person and videoconference sessions (Figure 2). In-person sessions will be delivered at four sites (Princess Alexandra Hospital, Ipswich Hospital, the University of Queensland St Lucia campus, and Griffith University Nathan campus), with oversight from A/Prof Nicola Burton (CHP), Dr Hannah Mayr (DN), Prof Jeff Coombes (EP, and Prof Coral Gartner (tobacco treatment specialist). Participants will be able to select their preferred in-person group location and time from the multiple time options offered and will be encouraged to attend the sessions at the same site throughout the intervention phase. Online and in person groups will be capped at 10 people.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants will complete the full intervention schedule of resilience, exercise training, nutrition, smoking cessation and behavior change support over a 20-week period.\u003c/p\u003e\n\u003cp\u003eMultidisciplinary Intervention 1. :- Resilience\u003c/p\u003e\n\u003cp\u003eThis group component is scheduled at the beginning to introduce key wellbeing concepts over the first eight weeks of the intervention. Each week participants will attend both an onsite group session and an online group session. It aims to provide support on adjustment to RA, and to provide a foundation for coping strategies relevant across the other components. Drawing from Acceptance and Commitment Therapy, Cognitive Behavior Therapy and Behavior Activation principles, sessions will focus on the role of mental health in RA self-management, mindfulness, acceptance, cognitive flexibility, coping strategies, life values and meaningful actions, social support, and sleep. Sessions will include information giving, personal reflection, experiential activities, skill rehearsal, feedback and problem-solving and applied practice \u0026ldquo;homework\u0026rdquo;.\u0026nbsp; A written handbook on session content and activities will be provided. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultidisciplinary Intervention 2. :- Exercise Training\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe twelve-week exercise training component will commence in week 9. Initially a 1-hour individual session will determine participants\u0026rsquo; exercise capacity, muscular fitness, exercise goals and preferences. Their individualized exercise prescription will be based on medical history, interests/preferences, physical capacity, and suitability for self-direction. Participants will then attend group exercise training sessions, within a mixture of weekly onsite and online group sessions. Each session will target recommendations of \u0026ge;150 minutes/week of moderate to vigorous aerobic and muscle strengthening exercise. Aerobic exercise will focus on walking unless significant lower limb musculoskeletal impairment preventing walking or stationary cycling, in which case suitable alternatives will be identified based on participant capabilities and access to resources. Strength exercises will involve upper and lower limbs using body weight and provided Therabands and small weights for use on site and at home. A Fitbit will also be provided to participants to facilitate self-monitoring.\u003c/p\u003e\n\u003cp\u003eMultidisciplinary Intervention 3. :- Nutrition\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe nutrition intervention will also commence in week 9 and will run over twelve weeks. \u0026nbsp;Initially, a 1-hour individual participant consultation will assess nutrition and set personalized goals. This will be followed up with two further 30-minute individual consultations and also three 1-hour group sessions that provide nutrition education and practical strategies, related to swapping or replacing foods, food preparation and recipes, label reading, shopping and eating out. Counselling will recommend alignment with principles of a Mediterranean-style diet (25, 26), including promoting higher intake of foods with anti-inflammatory properties (vegetables, fruits, nuts and seeds, legumes, fish and seafood, whole grain breads and cereals, herbs/spices, extra virgin olive oil), moderate intake of unflavored dairy foods, poultry and eggs, and lower intake of pro-inflammatory or ultra-processed foods including processed meats, red meat, sugary drinks, and other packaged or commercial foods and drinks high in saturated fat, sugar and/or sodium. Recommendations will be foods-focused to promote overall diet quality without a specific target macronutrient profile. The recommendations will be individualized and tailored; evidence-based resources and recipes which align with the Mediterranean-style diet principles (e.g. from Queensland Health Nutrition Education Materials Online and National Heart Foundation) will be provided where appropriate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultidisciplinary Intervention 2. :- Smoking Cessation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants who smoke will also commence a seven-week smoking cessation program, in week 9. Initially, a group education session will be offered. \u0026nbsp;This will be followed by weekly individual consultations. Sessions will include nicotine dependence assessment, quitting self-efficacy, lung age calculator, individual Quit Plan, education, support, and practical coping strategies. Over-the-counter stop smoking Nicotine Replacement Therapy options will be recommended and demonstrated. Dosing is based on World Health Organization \u0026ldquo;first line therapy\u0026rdquo; and Royal Australasian College of General Practitioner guidelines, including combination patches plus oral nicotine replacement, which is one of the most successful approaches to quit smoking (27). Prescription Varenicline and Bupropion options will be supported in line with participant preferences, in consultation with the participant\u0026rsquo;s usual GP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultidisciplinary Intervention 4. :- Behavior Change Support\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBehavior change support sessions will be conducted during the final month of the intervention, starting in week 17. \u0026nbsp;These sessions will be delivered by the same clinical/health psychologist who provided resilience training in week 1 of the intervention. They will focus on integrating wellbeing and healthy lifestyle activities into everyday life, and responding to related challenges. Content is based on the 5A Counselling Framework, which is an evidence-based approach appropriate for chronic conditions and endorsed by the RACGP and US Task Force on Preventive Health Care. The key components of the 5A framework include:\u0026nbsp;\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cu\u003eAssessment\u003c/u\u003e: change experiences/barriers/enablers\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eAdvice\u003c/u\u003e: clear recommendations for change\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eAgree\u003c/u\u003e: Collaborative agenda setting\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eAssistance\u003c/u\u003e: Cognitive and behavioral change strategies as indicated e.g. motivational interviewing, goal setting, action planning, positive expectations, problem-solving, self-monitoring, social support, self-talk\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eArrange\u003c/u\u003e: Additional assistance/resources as relevant.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eAt the completion of the intervention period, participants will be invited to attend an online focus group to discuss intervention experiences and associated barriers and enablers to engagement in the interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTUDY ARMS: PROGRAM B: ONGOING BEST PRACTICE USUAL CARE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants in Program B will receive brief monthly check-ins by email to inform of appointment times for follow-up and to monitor AEs. Participants will be referred to their general practitioner or rheumatologist should they need further management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria for discontinuing or modifying allocated interventions {11b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e\n\u003cp\u003eExplanation: This study does not trial any medicinal products and as detailed in the above intervention description, all components of the multidisciplinary intervention will be personalized to accommodate individual participants\u0026rsquo; needs. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategies to improve adherence to interventions {11c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne of the barriers to program adherence is the significant time commitment required. Details have been provided at informed consent and will be discussed verbally during screening. A support person (e.g. family member or friend) is encouraged to be at the consent meeting to assist with information retention. Letters to the participant\u0026rsquo;s treating rheumatologist and general practitioner will encourage support from other members of the health care team. The person-centred approach used in Program A (e.g. individualised exercise training and nutrition) is intended to take into account individual concerns and preferences and empower participant participation. Offering options for different times and locations for in-person interventions, including weekends, as well as some sessions via videoconference to reduce travel burden, are intended to facilitate adherence. Commencing with resilience is intended to provide intrapersonal strategies to assist with engagement to the lifestyle component.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelevant concomitant care permitted or prohibited during the trial {11d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipation in RA-HEAL is considered an adjunct to a participant\u0026rsquo;s continuous medical care from their usual rheumatologist (once stable on conventional or biological DMARDs, appointments are typically every 3-6 months), general health care with their usual general practitioner and any additional\u0026nbsp;support services and activities (including related to healthy eating, exercise, smoking cessation, wellbeing) initiated by them before or during the intervention period..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProvisions for post-trial care {30}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter the trial all participants will continue to receive RA treatment with their usual rheumatologist, general health care with their usual general practitioner and any additional\u0026nbsp;support services and activities initiated by them.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes {12}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome is physical health-related QoL at 6 months, as determined by the SF-36 v2 physical component score.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecondary outcomes include:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cem\u003ePhysical health-related QoL\u003c/em\u003e: as well as the primary outcome of testing at 6 months, SF-36 v2 physical component score at 12, 18 and 24 months will also be measured\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eConfidence for self-management of RA\u003c/em\u003e: the Perceived Competence Scales will assess confidence in taking an active role in managing wellbeing, exercise, healthy eating, medications and (if relevant) smoking cessation in the context of having RA at 6, 12, 18 and 24 months.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003ePhysical function and anthropometry:\u0026nbsp;\u003c/em\u003eexercise capacity (6-Minute Walk Test (6MWT)), neuromuscular strength (grip strength with a dynamometer), power (Timed-Up \u0026amp; Go (TUG) test) and strength endurance (5 times sit to stand test and 30 second arm curl test),\u0026nbsp;gait speed (4 metre walk test) and balance (single leg balance test); height, weight, and waist circumference at 6, 12, 18 and 24 months.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eMental health:\u0026nbsp;\u003c/em\u003eSF36v2 mental health component score, the Warwick-Edinburgh Mental Wellbeing Scale and the Perceived Stress scale at 6, 12, 18 and 24 months.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003ePhysical activity\u003c/em\u003e: physical activity and sedentary behavior will be assessed; (i) objectively via Actigraph accelerometry over one week at baseline and at 6 months, and (ii) by self-report using items from the National Health Survey at 6, 12, 18 and 24 months (28).\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eDiet quality\u003c/em\u003e: the 50-item Mediterranean Diet and Culinary Index (MediCul) at 6, 12, 18 and 24 months, to provide a score between 0 to 100 (29). The tool also allows for calculation of a commonly reported validated 14-item Mediterranean diet adherence score (30).\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eSmoking cessation\u003c/em\u003e: self-report at 6, 12, 18 and 24 months, (7-day and continuous abstinence), including number of cigarettes smoked, nicotine dependence, quitting self-efficacy i.e., self-confidence about making another quit attempt (if quit attempt was unsuccessful); biochemically verified exhaled carbon monoxide.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eRA disease activity score (DAS28CRP)\u003c/em\u003e: a composite measure of patient global score, tender and swollen joint counts and C-reactive protein, at 6, 12, 18 and 24 months. DAS-remission will be defined as a DAS \u0026lt; 2.4. Remission duration will be defined as the length of time over which a DAS \u0026lt; 2.4 is measured.\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eCardiovascular disease risk:\u003c/em\u003e will be measured using the Australian CVD Risk Calculator (31), which calculates CVD risk percentiles based on input variables.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eOverall health-related quality of life: Assessment of Quality-of-Life score 8 Dimension (AQoL-8D) score\u003c/em\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe will evaluate the 5 components of Reach, Effectiveness, Adoption, Implementation, Maintenance from the (RE-AIM) framework in the RA-HEAL study. \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eR\u003c/u\u003eeach refers to eligible people willing to engage with programs. It will be measured firstly as the number of people who consent to the trial as a function of the number of queries from eligible potential participants. Participant representativeness will compare sociodemographic, lifestyle and clinical profile of the trial participants with the A3BC database of RA participants with RA onset in the last 12 months. Reach in each arm will be assessed as the proportion of participants recruited to the study who (i) in program A engage with each component (resilience, exercise training, nutrition, smoking cessation, and behaviour change) and (ii) in program B seek engagement with professional services related to mental health, exercise, nutrition or smoking cessation support for RA, including through The Arthritis Movement programs or private service providers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eE\u003c/u\u003effectiveness refers to short-term impact. It will be measured as the change from baseline at 6, 12, 18 and 24 months using the measures specified in the primary and secondary outcome measures.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eA\u003c/u\u003edoption refers to an \u003cem\u003eagency\u0026rsquo;s\u003c/em\u003e use of an intervention. It will be measured as:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNumber and characteristics of staff implementing the program.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eI\u003c/u\u003emplementation refers to the delivery of the intervention. It will be measured as:\u0026nbsp;\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cem\u003eFidelity\u003c/em\u003e: An online checklist from multidisciplinary interventionists will be used to assess the consistency of Program A delivery (e.g. number of sessions provided, content covered) against written protocols. Provision of written information resources to participants will be recorded.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eFeasibility:\u0026nbsp;\u003c/em\u003e\u0026nbsp;\u003col style=\"list-style-type: lower-alpha;\"\u003e\n \u003cli\u003eThe proportion of participants completing each component of and the entire program A relative to the number allocated to and commencing program A, and \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe proportion of participants engaging with Program A sessions as a function of the total number of sessions for each of the program A components.\u0026nbsp;\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n \u003cli\u003e\u003cem\u003eAcceptability:\u0026nbsp;\u003c/em\u003e\n \u003col style=\"list-style-type: lower-alpha;\"\u003e\n \u003cli\u003eParticipant feedback on satisfaction with and perceived helpfulness of their program and resources for RA self-management.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eProgram A intervention experiences, and associated barriers and enablers to engagement across the various component sessions. \u0026nbsp;\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cem\u003eCost effectiveness\u003c/em\u003e: Modified cost diaries capturing health resources accessed, supplemented by Medicare Benefit Schedule (MBS) and Pharmaceutical Benefit Scheme (PBS) data. Health resources will be valued using market prices and industrial wages. Utility scores to allow quality-adjusted life years (QALYs) gained will be obtained using SF-6Dv2, a subset of SF36v2 using Australian weights. An exploratory analysis will compare the performance of SF-6Dv2 and AQoL-8D\u003cu\u003e.\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eM\u003c/u\u003eaintenance refers to \u003cem\u003esustained\u003c/em\u003e change and will compare the primary and secondary effectiveness measures at 6, 12, 18 and 24 months.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSchedule of enrolment, interventions, and assessments (SPIRIT Figure)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant timeline {13}\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eOn-study\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eExit\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eEvaluation\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAssessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eScreening\u003c/strong\u003e\u003cstrong\u003eᵃ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMonth 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMonth\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMonth\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMonth\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMonth\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVisit 6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEligibility Assessment/ Confirmation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInformed consent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInitial Participant screening survey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePhysical Examination (symptom directed)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eVital Signs/Body Weight/Height\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSOC RA bloods:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(FBP, ESR, CRP, ELFT, Lipid profile)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eRF anti-CCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eA3BC blood sampling and oral swab (PBMC, DNA, serum processing and store) for exploratory immune and biomarker assays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eA3BC stool sampling for microbiome and metabolomics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eECG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePhysical function scores (6MWT, TUG, grip strength, 5XSST, 30 sec arm curl, single leg balance, 4m gait speed test)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eApplication of Actigraph monitor (7 days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003cp\u003e(week 20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eExhaled CO2 (Smokers only)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAdverse Event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eRandomisation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eXᵇ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\n \u003cp\u003eRA-HEAL-A3BC Questionnaireͨ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMedical History (symptom directed, CVD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eXͩ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eXͩ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eXͩ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eXͩ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eConcurrent Medications\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDisease activity score (SJC, TJC, VAS, RADAI, RAPID3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEmployment Status, Financial benefits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDiet\u0026nbsp;quality\u0026nbsp;(MediCul)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCost\u0026nbsp;utility\u0026nbsp;(SF36v2,\u0026nbsp;AQoL-8D)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWarwick Edinburgh Mental Wellbeing Scale (WEMWBS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePerceived Stress Scale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePerceived Competence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eProfessional Assistance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNational Health Survey (exercise)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSocial Support Questionnaire\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEquity Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFeedback survey (all participants) \u0026ndash; additional services/resources accessed and satisfaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFeedback survey program A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFocus group session\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFootnotes:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eᵃ\u0026nbsp;\u003c/strong\u003eScreening Visit is completed via telehealth/online\u003c/p\u003e\n\u003cp\u003eᵇ\u0026nbsp;Participants will be randomised before their Baseline Visit onsite once verbal consent is obtained at their Screening visit (telehealth/online).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eͨ\u0026nbsp;RA-HEAL A3BC questionnaire can be completed online before the in-person assessments at Baseline, Month 6, 12, 18, and 24 or in-person during their in-person visits at the same timepoints.\u003c/p\u003e\n\u003cp\u003eͩ\u0026nbsp;Only collecting significant change to participant\u0026rsquo;s medical history.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size {14}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSample sizes of 62 participants for each of Program A and B were estimated based on pilot program physical health-related QoL SF36 data (32), to achieve 80% power to detect a superiority margin of 40% improvement using a one-sided, two-sample t-test. The true difference between the means is assumed to be 26.39 and standard deviation assumed to be 20.53. The significance level (alpha) of the test is 0.025 (as one sided). With a 20% dropout rate based on the pilot intervention and among local patients with new-onset RA recruited to the A3BC cohort study, 78 participants are needed per arm (156 in total).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSequence generation {16a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be block randomized in blocks of 4, stratified for current smoking history to ensure similar representation in each arm, and allocated 1:1 to Program A or Program B, according to a computer-generated randomization table. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcealment mechanism {16b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be randomised according to a computer-generated randomization table held centrally by the senior statistician and data manager (concealed group allocation) then informed as to their group, along with options for group sessions for Program A participants, by the unblinded trial administrative officer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of interventions: Blinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWho will be blinded {17a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter randomisation, the administrative officer, participants and interventionists will be aware of Program allocation. In order to minimize bias the PI, outcome assessors, laboratory personnel and statistical personnel will be blinded as to allocation of individual participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for assessment and collection of outcomes {18a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAssessments (Figure 3) conducted at baseline, 6, 12, 18 and 24 months, and carried out by the PI and outcome assessors will be in-person at the Clinical Research Facility, Princess Alexandra Hospital.\u003c/p\u003e\n\u003cp\u003eQuestionnaires will collect:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eBasic demographics including age, gender, duration of RA, financial benefit status\u003c/li\u003e\n \u003cli\u003eHealth related Quality of Life, physical (SF36 v2)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHealth related Quality of Life (AQo-8D)\u003c/li\u003e\n \u003cli\u003eMedication\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRA disease activity indices\u003c/li\u003e\n \u003cli\u003eEmployment status, including work productivity/activity impairment\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePhysical activity/sitting time \u0026ndash; National Health Survey\u003c/li\u003e\n \u003cli\u003eDiet quality \u0026ndash; MediCul Index\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMental health (SF36 v2), Mental Wellbeing Scale, Perceived Stress Scale)\u003c/li\u003e\n \u003cli\u003eConfidence for Self-Management of Arthritis Scale\u003c/li\u003e\n \u003cli\u003eUse of professional services/assistance for mental health, exercise, nutrition, smoking cessation engagement\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCigarettes smoked/nicotine dependence/quitting self-efficacy\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eProgram A participant attendance records, adverse events, adherence to nicotine replacement products, and exercises completed will be monitored by the interventionists. Program A participants will be invited to participate in a focus group discussion to provide additional feedback at Month 6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to promote participant retention and complete follow-up {18b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe intervention is patient-centred and will offer options for different locations for on-site visits, and for some sessions to be delivered via videoconference. Investigators will make every reasonable effort to keep each participant in the study unless there is a safety concern with continuing. After 2 consecutive non-attendances, participants will be contacted by Short Message Service (SMS). Participants will continue to be offered the opportunity to attend assessments unless they advise they wish to withdraw from the trial. If an adverse event is the reason for a participant\u0026rsquo;s withdrawal the investigator will encourage the participant to be followed up for the full study period and complete the exit evaluation at 24 months post intervention. If a participant withdraws from RA-HEAL, separate withdrawal from A3BC will be discussed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData management {19}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy survey data are captured electronically into the secure web application REDCap. The surveys will be completed at each in-person study visit. The study monitor will review data on a regular ongoing basis and for clarification and correction (where applicable) until database lock.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConfidentiality {27}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be allocated unique RA-HEAL and A3BC participant identification numbers (IDs). Only participating clinicians and project staff will be directly aware of participant identities. All data will be stored in a re-identifiable format for participant tracking and follow-up. These IDs will be used on all documentation and biological samples. Any researcher access to participant data will be in a non-individually identifiable format. No patient information will be released carrying personal identifiers unless pertinent to care (see below). Results of research analyses will not be fed back individually to participants, but aggregate reports may be published in peer-reviewed journals, and/or presented to appropriate audiences. It will not be possible to re-identify individuals from such reports.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLinked administrative health data will be accessible where participants have authorised this on the A3BC consent form. \u0026nbsp;Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data for the cost-utility analysis may be linked via Services Australia or the Australian Institute of Health and Welfare (AIHW).\u0026nbsp;Linked data will be stored and/or accessed in accordance with the A3BC\u0026rsquo;s data linkage ethics approvals and applicable data custodian requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBiological samples stored with linked clinical data at baseline, 6-, 12-, 18- and 24-months include Peripheral Blood Mononuclear Cells (PBMC), serum, plasma, stabilised whole blood RNA, DNA (baseline) and stool. Planned laboratory evaluations include immune cell populations (including autoantigen-specific T cells) by flow cytometry, serum/plasma soluble analytes, stool and serum metabolomics including short chain fatty acids and lipidomics. All analyzed data will be uploaded to the A3BC database\u003cu\u003e.\u003c/u\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical methods for primary and secondary outcomes {20a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore modelling trial outcomes, baseline demographic, lifestyle and clinical characteristics of Program A and Program B participants will be compared to establish whether randomization succeeded in creating comparable groups. Any characteristics not comparable at baseline will be modelled as covariates in subsequent analyses to adjust for possible confounding effects. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOutcomes will be assessed using linear mixed modelling (LMM) and will be used to evaluate effectiveness of the intervention on the primary and secondary outcomes, which are continuous. LMM will examine whether changes in the outcomes of interest vary over time as well as across the two groups, after adjusting for the effects of any potential confounders. This approach is chosen due to its robustness in handling unbalanced data and its ability to model both the fixed effects of intervention and time, as well as random effects that account for inter-subject variability. Intervention effects will be assessed post-intervention (6 months) and during the maintenance period (12, 18 and 24 months). Model fit will be assessed using the Aikake and Bayesian Information Criteria, and diagnostic plots will check for deviations from model assumptions. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn economic evaluation form from the health care system perspective will be conducted to determine the incremental cost per additional quality adjusted life year (QALY) gained for Program A over Program B and will include\u0026nbsp;deterministic linked MBS and PBS data. Nonparametric bootstrapping will used to characterize the uncertainty in the economic evaluation results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterim analyses {21b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome and 6-month secondary outcomes will be determined once all participants have completed 6-month assessment. Data collection will continue 6-monthly until the 2-year visit, at which time the extended longitudinal outcomes will be determined. A value-of-information analysis will be conducted as an extension to the economic evaluation to assess whether the evidence is sufficient to inform decision-making for implementation or if more data should be collected.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods for additional analyses (e.g. subgroup analyses) {20b}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants who smoke, who were purposively sampled and balanced between intervention groups and who receive specific intervention will be analyzed together with all participants, and as a separate subgroup. To identify any other relevant subgroups, at the primary endpoint, key clinical and demographic data will be clustered using an unbiased approach to determine variables, other than the intervention, contributing to the primary outcome using outcome-guided clustering. This will build a random survival forest and compute the distances between all observations based on the fitted model. Based on the distances, hierarchical clustering identifies clusters of samples with similar characteristics and survival rate. Further subgroup analysis will be based on the outcome of the clustering.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe basis of statistical analysis will be intention-to-treat for those\u0026nbsp;participants attending at least 25% of the sessions from all components.\u0026nbsp;Missing values will be examined for their patterns and distributions, and multiple imputation will be used if all relevant assumptions are met.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans to give access to the full protocol, participant level data and statistical code {31c}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFull protocol, participant level data, and statistical code will be accessible after trial completion upon request per the A3BC Access Policy. New analyses must be reviewed and approved by a human research ethics committee, the A3BC Consortium Committee and Access Committee prior to release of samples and/or data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOversight and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the coordinating center and trial steering committee {5d}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe coordinating centre at the University of Queensland comprises a clinical nurse coordinator, administrative officer, PI, sub-PI and clinical research assistant. The REDCap data management platform, A3BC data manager and biobank manager are located at the University of Sydney. The A3BC steering/consortium committee comprises clinical leads from each state in Australia, including the RA-HEAL lead investigator, Ranjeny Thomas in Queensland. The Trial Steering Committee comprises the PI and sub-PI and lead CHP, DN, EP and smoking interventionalists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComposition of the data monitoring committee, its role and reporting structure {21a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data monitoring committee comprises the data monitor and A3BC data manager. They report to the Trial Steering Committee and are independent of the sponsor. They are governed by a data monitoring charter.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse event reporting and harms {22}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe procedure for reporting AEs is provided with the Participant Information Sheet along with a central study email address and the contact details of local research team members. Participants are encouraged to record any adverse events (AEs e.g. injury) or serious adverse event (SAEs) to a member of the research team (e.g. the relevant interventionist/s or project coordinator). \u0026nbsp; All participants are also provided with a diary to record AEs/SAEs. \u0026nbsp;The coordinator will keep a record of all reported AEs. Participants will be referred to their general practitioner or rheumatologist should they need further management. AEs include any occurrences that are new in onset or aggravated in severity or frequency from the baseline condition, or abnormal results, including laboratory test abnormalities. Pre-existing conditions or diseases that occur during the study (e.g., arrhythmias, rheumatoid arthritis) will not be considered as AEs unless they change in frequency or severity. Elective surgery or other scheduled hospitalisation periods that were planned before the participant was included in this trial are not to be recorded as SAEs, unless an outcome is considered serious.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSAEs will be reported to the approving Human Research Ethics Committee within 15 calendar days of the sponsor becoming aware of the issue. All SAE documents are stored in the participant\u0026rsquo;s study record and are retained as per the Study Record Retention policy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFrequency and plans for auditing trial conduct {23}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no plans for independent auditing, but the trial may be audited at random by the Human Research Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be informed by email of any relevant protocol amendments approved by the Human Research Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDissemination plans {31a}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will receive a written lay summary of the main outcomes of the trial in an email newsletter and will be invited to community-based presentations on the trial aims and outcomes. Trial outcomes will be published in scientific literature and doctoral theses, presented to clinical and academic audiences at conferences and seminars, and reports formatted for consumption by lay audiences and policy makers.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRA-HEAL tests whether a tailored intervention including formal resilience training with a clinical psychologist followed by exercise, nutrition counselling, smoking cessation and behavior change support has a greater effect on health-related QoL than written advice given in current best-practice settings. RA management recommendations reinforce the importance of early diagnosis and early treatment to a target of remission, in order to minimise inflammation, reduce risk of long-term complications and maximise QoL (33, 34). A unique feature of RA-HEAL is that it targets RA within 12 months of onset. Diagnosis provides a strong opportunity for physician-patient interaction (“teachable moment”) to initiate steps towards behavior change (35). Furthermore, although long-term adherence to lifestyle changes is critical for prolonged benefits to microbiome, cardiovascular and immune health, most existing trials of lifestyle intervention have relatively short duration of follow-up. RA-HEAL’s linkage with A3BC provides the framework to support not only the 6 monthly follow-up data and biological sampling to 24 months post-intervention for RA-HEAL Trial, but the opportunity for further annual surveys beyond 24 months with A3BC, creating a valuable resource for future research. Thus, in its secondary outcomes, RA-HEAL will assess the longevity of effects of intervention or best-practice usual care for up to 2 years, with the option for ongoing, longer-term surveys and data linkages through A3BC\u003c/p\u003e\n\u003cp\u003eDepression in RA is associated with poorer disease outcomes (36) and the rates of depression and anxiety are higher in patients with RA than controls, attributable to pain, fatigue, functional limitation, reduced capacity for work and reduced ability to participate in valued activities. Patients with low self-management behaviour also have higher risks of anxiety and depression (37). Whilst other multidisciplinary RCTs such as the PFJ and MADEIRA trials have provided general psychoeducation on stress and relaxation training (7, 9), the RA-HEAL resilience component extends this further by offering a more structured patient-centred resilience training based on principles of CBT and ACT which are consistently recognised as evidence-based psychological treatments (38). Patient activation for self-management is the focus of the resilience training offered at the start of the RA-HEAL intervention and will be specifically assessed with a confidence for self-management scale.\u003c/p\u003e\n\u003cp\u003eChronic inflammation induced by gut dysbiosis and the negative impacts of inactivity have been implicated as potential causal factors in the development and progression of RA\u0026nbsp;(39, 40). The Mediterranean diet consists of higher consumption of fibre-rich plant-based-foods such as fruits, vegetables, legumes, nuts and whole grains, more moderate consumption of fish, poultry and dairy, and low consumption of red meat. It has been proposed as an intervention to modify intestinal microbiota and mitigate dysbiosis in the management of RA (41).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhysical activity benefits people with RA in terms of joint function and mobility but also mood and fatigue. It may benefit associated comorbid conditions such as cardiovascular disease, as well as overall QoL\u0026nbsp;(42). Physical activity may reduce disease activity and inflammation and improve symptoms, providing an effective tool in the management of RA (43). These outcomes support the recommendation of Mediterranean diet principles and exercise in both arms of RA-HEAL.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eComposite end-points such as health-related QoL are highly valued by patients with RA, as they incorporate a broad range of health outcomes, not only including pain and joint damage, but also their capability for activities of daily living, mobility, life enjoyment, independence, management of fatigue and participation in valued activities (44). Health-related\u0026nbsp;QoL, as assessed by the SF-36v2 scale\u0026nbsp;(45), is sensitive to adverse disease impacts in multiple domains, and thus is a useful primary-outcome target for assessing interventions\u0026nbsp;(46). The physical-component score primary outcome measure was particularly sensitive to change in the pilot intervention, in keeping with improvements in physical function\u0026nbsp;(15). As data are linked to multiple state and federal health data collections for those participants who elect to maintain their A3BC consent after completion of RA-HEAL, there will be opportunities to validate self-report of health-related events and medications, to determine medium and long-term effects of behavior change and to strengthen cost-utility analyses.\u003c/p\u003e\n\u003cp\u003eThe goal of effective lifestyle intervention is to reduce the burden of RA in individuals that includes distress, reduced function, disability, medical and allied health consultations, medications, surgery, and long-term complications, and the public-health burden of RA to the community. The outcomes of our comprehensive comparison of intervention and best practice usual-care programs in the RA-HEAL trial should provide evidence for a scalable approach to deliver, engage and sustain people with newly diagnosed RA in self-management. This may have implications for service delivery and specific health service roles. Implementing effective models of management over the long term would result in substantial cost savings for the healthcare system.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cb\u003eAdministrative information\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntroduction\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eTitle\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eKatherine A Poulsen, Nicola W Burton, Hannah L Mayr, Veronique S Chachay, Jeff S Coombes, Coral E Gartner, Amee Sonigra, Paul Christensen, Karl Hansford, Dianna J Ang, Jessica Neri, Ramali Mendis, Tom Lynch, Cheryl Dines, Helen Benham, Aoife Sweeney, Lyn M March, Asaduzzaman Khan, Haitham Tuffaha and Ranjeny Thomas.\u003c/em\u003e\u003c/p\u003e\u003cp\u003eMaintenance refers to \u003cem\u003esustained\u003c/em\u003e change and will compare the primary and secondary effectiveness measures at 6, 12, 18 and 24 months.\u003c/p\u003e\u003cp\u003eThe protocol and Participant Informed Consent Form were approved by the Metro South Human Research Ethics Committee.\u003c/p\u003e\u003cp\u003eNot applicable\u003c/p\u003e\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\u003cp\u003e\u003cb\u003eFunding\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFunded by Medical Research Future Fund (MRFF) Grant ID:2032246\u003c/p\u003e\u003cp\u003eThe funding body played no role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAuthors\u0026rsquo; contributions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eConcept, study and instrument design: RT, NB, JC, HM, VC, CG, KP, AoS, JN, HB, CD, LM, KH, DA, RM, TL, PC. Statistical design: AK. Health Economic Evaluation design: HT. Drafted manuscript: KP, RT. Obtained funding: RT. Edited manuscript: all authors.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial status\u003c/b\u003e\u003c/p\u003e\u003cp\u003eProtocol version: 1.3, dated March 12, 2025\u003c/p\u003e\u003cp\u003eRecruitment commencement: March 12, 2025\u003c/p\u003e\u003cp\u003eApproximate recruitment completion: July 01, 2026\u003c/p\u003e\u003cp\u003e\u003cb\u003eAbbreviations\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Trial status","content":"\u003cp\u003eProtocol version: 1.3, dated March 12, 2025\u003c/p\u003e\n\u003cp\u003eRecruitment commencement: March 12, 2025\u003c/p\u003e\n\u003cp\u003eApproximate recruitment completion: July 01, 2026\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate {24}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol and Participant Informed Consent Form were approved by the Metro South Human Research Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication {32}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials {29}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll trial investigators will have access to the final dataset, as agreed in the Multi-Institutional Agreement and Clinical Trial Research Agreement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests {28}\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunded by Medical Research Future Fund (MRFF) Grant ID:2032246\u003c/p\u003e\n\u003cp\u003eThe funding body played no role in the design of the study, collection, analysis, interpretation of data, or in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept, study and instrument design: RT, NB, JC, HM, VC, CG, KP, AoS, JN, HB, CD, LM, KH, DA, RM, TL, PC. Statistical design: AK. Health Economic Evaluation design: HT. Drafted manuscript: KP, RT. Obtained funding: RT. Edited manuscript: all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Roberta Littleford for critical reading of the protocol.\u003c/p\u003e\n\u003cp\u003eCorresponding author: Ranjeny Thomas; [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAustralian Institute of Health and Welfare. Chronic musculoskeletal conditions : Rheumatoid arthritis [Web]. AIHW, Australian Government; 2024 [updated 28/05/2024. Available from: https://www.aihw.gov.au/reports/chronic-musculoskeletal-conditions/rheumatoid-arthritis.\u003c/li\u003e\n\u003cli\u003eKoller-Smith L, Mehdi A, March L, Tooth L, Mishra GD, Thomas R. A novel method to monitor rheumatoid arthritis prevalence using hospital and medication databases. Arthritis Res Ther. 2024;26(1):133.\u003c/li\u003e\n\u003cli\u003eSparks JA, Iversen MD, Yu Z, Triedman NA, Prado MG, Miller Kroouze R, et al. Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial. Arthritis Care Res (Hoboken). 2018;70(6):823-33.\u003c/li\u003e\n\u003cli\u003eZangi HA, Ndosi M, Adams J, Andersen L, Bode C, Bostr\u0026ouml;m C, et al. EULAR recommendations for patient education for people with inflammatory arthritis. Ann Rheum Dis. 2015;74(6):954-62.\u003c/li\u003e\n\u003cli\u003eAustralian Institute of Health and Welfare. Use of chronic disease management and allied health Medicare services [Web]. Australian Institute of Health and Welfare Reports: AIHW, Australian Government; 2022 [updated 15/12/2022. Available from: https://www.aihw.gov.au/reports/chronic-disease/medicare-chronic-disease-allied-health-items/contents/about.\u003c/li\u003e\n\u003cli\u003e1 in 3 psychologists are unable to see new clients, but Australians need help more than ever. Australian Psychological Society. 2022 [updated 24 February 2022. Available from: https://psychology.org.au/for-members/news-and-updates/news/2022/australians-need-psychological-help-more-than-ever.\u003c/li\u003e\n\u003cli\u003eWalrabenstein W, Wagenaar CA, van der Leeden M, Turkstra F, Twisk JWR, Boers M, et al. A multidisciplinary lifestyle program for rheumatoid arthritis: the \u0026apos;Plants for Joints\u0026apos; randomized controlled trial. Rheumatology (Oxford). 2023;62(8):2683-91.\u003c/li\u003e\n\u003cli\u003eWalrabenstein W, van der Leeden M, Weijs P, van Middendorp H, Wagenaar C, van Dongen JM, et al. The effect of a multidisciplinary lifestyle program for patients with rheumatoid arthritis, an increased risk for rheumatoid arthritis or with metabolic syndrome-associated osteoarthritis: the \u0026quot;Plants for Joints\u0026quot; randomized controlled trial protocol. Trials. 2021;22(1):715.\u003c/li\u003e\n\u003cli\u003ePapandreou P, Gioxari A, Daskalou E, Grammatikopoulou MG, Skouroliakou M, Bogdanos DP. Mediterranean Diet and Physical Activity Nudges versus Usual Care in Women with Rheumatoid Arthritis: Results from the MADEIRA Randomized Controlled Trial. Nutrients. 2023;15(3).\u003c/li\u003e\n\u003cli\u003ePineda-Ju\u0026aacute;rez JA, Lozada-Mellado M, Hinojosa-Azaola A, Garc\u0026iacute;a-Morales JM, Ogata-Medel M, Llorente L, et al. Changes in hand grip strength and body weight after a dynamic exercise program and Mediterranean diet in women with rheumatoid arthritis: a randomized clinical trial. 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Aust N Z J Public Health. 2004;28(2):128-34.\u003c/li\u003e\n\u003cli\u003eRadd-Vagenas S, Fiatarone Singh MA, Daniel K, Noble Y, Jain N, O\u0026apos;Leary F, et al. Validity of the Mediterranean Diet and Culinary Index (MediCul) for Online Assessment of Adherence to the \u0026apos;Traditional\u0026apos; Diet and Aspects of Cuisine in Older Adults. Nutrients. 2018;10(12).\u003c/li\u003e\n\u003cli\u003eEstruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. 2018;378(25):e34.\u003c/li\u003e\n\u003cli\u003eAusCVDRisk Calculator [Website]. Australian Chronic Disease Prevention Alliance; [Available from: https://www.cvdcheck.org.au/calculator.\u003c/li\u003e\n\u003cli\u003eThomas R, Burton, Nicola, Mayr, Hannah, Chachay, Veronique, Sweeney, Aoife, Hollis, Kely, Gartner, Coral, Coombs, Jeff. A pilot blended-delivery wellbeing and healthy lifestyle program for adults with rheumatoid arthritis. [Poster Presentation]. Internal Medicine Journal. 2023;53(s1):1.\u003c/li\u003e\n\u003cli\u003ePeters MJ, Symmons DP, McCarey D, Dijkmans BA, Nicola P, Kvien TK, et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis. 2010;69(2):325-31.\u003c/li\u003e\n\u003cli\u003eSmolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964-75.\u003c/li\u003e\n\u003cli\u003eFlocke SA, Clark E, Antognoli E, Mason MJ, Lawson PJ, Smith S, et al. Teachable moments for health behavior change and intermediate patient outcomes. Patient Educ Couns. 2014;96(1):43-9.\u003c/li\u003e\n\u003cli\u003eMatcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2013;52(12):2136-48.\u003c/li\u003e\n\u003cli\u003eVestergaard SB, Esbensen BA, Klausen JM, Glintborg B, Lau L, Yilmaz Jantzen C, et al. Prevalence of anxiety and depression and the association with self-management behaviour in \u0026gt;12 000 patients with inflammatory rheumatic disease: a cross-sectional nationwide study. RMD Open. 2024;10(1).\u003c/li\u003e\n\u003cli\u003eNagy Z, Szigedi E, Takacs S, Csaszar-Nagy N. The Effectiveness of Psychological Interventions for Rheumatoid Arthritis (RA): A Systematic Review and Meta-Analysis. Life (Basel). 2023;13(3).\u003c/li\u003e\n\u003cli\u003eZaiss MM, Joyce Wu HJ, Mauro D, Schett G, Ciccia F. The gut-joint axis in rheumatoid arthritis. Nat Rev Rheumatol. 2021;17(4):224-37.\u003c/li\u003e\n\u003cli\u003eDi Giuseppe D, Bottai M, Askling J, Wolk A. Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study. Arthritis Res Ther. 2015;17:40.\u003c/li\u003e\n\u003cli\u003eGuerreiro CS, Calado A, Sousa J, Fonseca JE. Diet, Microbiota, and Gut Permeability-The Unknown Triad in Rheumatoid Arthritis. Front Med (Lausanne). 2018;5:349.\u003c/li\u003e\n\u003cli\u003eBjork M, Dragioti E, Alexandersson H, Esbensen BA, Bostrom C, Friden C, et al. Inflammatory Arthritis and the Effect of Physical Activity on Quality of Life and Self-Reported Function: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken). 2022;74(1):31-43.\u003c/li\u003e\n\u003cli\u003eSveaas SH, Smedslund G, Hagen KB, Dagfinrud H. Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis. Br J Sports Med. 2017;51(14):1065-72.\u003c/li\u003e\n\u003cli\u003eSanderson T, Morris M, Calnan M, Richards P, Hewlett S. Patient perspective of measuring treatment efficacy: the rheumatoid arthritis patient priorities for pharmacologic interventions outcomes. Arthritis Care Res (Hoboken). 2010;62(5):647-56.\u003c/li\u003e\n\u003cli\u003eLinde L, Sorensen J, Ostergaard M, Horslev-Petersen K, Hetland ML. Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, EQ-5D [corrected] RAQoL, and HAQ in patients with rheumatoid arthritis. J Rheumatol. 2008;35(8):1528-37.\u003c/li\u003e\n\u003cli\u003eMatcham F, Scott IC, Rayner L, Hotopf M, Kingsley GH, Norton S, et al. The impact of rheumatoid arthritis on quality-of-life assessed using the SF-36: a systematic review and meta-analysis. Semin Arthritis Rheum. 2014;44(2):123-30.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Rheumatoid arthritis, lifestyle intervention, diet, exercise, behavior change, resilience training, biosamples, quality-of-life","lastPublishedDoi":"10.21203/rs.3.rs-6552255/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6552255/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe importance of self-management strategies that optimize physical health and mental health in the management of rheumatoid arthritis (RA) is recognized, but access to multidisciplinary teams to support this can be challenging. Furthermore, evidence for the impact of multidisciplinary interventions, especially in early RA, is lacking.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe Resilience and Healthy Lifestyle for Rheumatoid Arthritis (RA-HEAL) Trial is a pragmatic RCT that aims to compare effects of a structured multidisciplinary lifestyle intervention with self-directed activities in best-practice usual care. The 20-week multi-modal intervention incorporates structured resilience training conducted by a clinical health psychologist (CHP), followed by an exercise physiologist (EP)-led exercise program, dietary education conducted by a dietitian nutritionist (DN), smoking cessation program (where applicable) and psychologist-led behavior-change support. The comparison group will receive written information on healthy lifestyle in accordance with standard best practice care. The primary outcome is health-related quality of life (QoL) at 6 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eRA-HEAL tests whether a tailored intervention including formal resilience training with a clinical psychologist followed by Mediterranean diet, exercise, smoking cessation and behavior change support has a greater effect on health-related QoL at 6 months, than written advice given in current best-practice settings. QoL is a composite endpoint that is highly valued by patients with RA. RA-HEAL is unique in it targets RA within 12 months of onset. RA-HEAL’s linkage with the Australian Autoimmune Arthritis Biobank Cooperative (A3BC) supports 6 monthly follow-up data and biosampling to 24 months post-intervention and linkage to health data collections, creating a valuable resource for future research and the potential to determine medium and long-term effects of behavior change. In its secondary outcomes, RA-HEAL will analyze the longevity of effects of intervention or best-practice usual care for up to 2 years, and cost utility. The outcomes should provide evidence to underpin a scalable approach to support people with newly-diagnosed RA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: ACTRN12625000050459, ANZCTR\u003c/p\u003e","manuscriptTitle":"Resilience And Healthy Lifestyle for Rheumatoid Arthritis (The RA-HEAL trial): a randomised, parallel group, placebo-controlled clinical trial protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 01:43:28","doi":"10.21203/rs.3.rs-6552255/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-07-11T14:46:41+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-11T14:46:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-10T06:15:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-06-09T16:32:27+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor revision","date":"2025-06-04T10:25:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"807db4fd-cc98-4957-89fd-d6e6d81ac84c","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:00:02+00:00","versionOfRecord":{"articleIdentity":"rs-6552255","link":"https://doi.org/10.1186/s13063-025-09063-7","journal":{"identity":"trials","isVorOnly":false,"title":"Trials"},"publishedOn":"2025-09-29 15:57:08","publishedOnDateReadable":"September 29th, 2025"},"versionCreatedAt":"2025-07-22 01:43:28","video":"","vorDoi":"10.1186/s13063-025-09063-7","vorDoiUrl":"https://doi.org/10.1186/s13063-025-09063-7","workflowStages":[]},"version":"v1","identity":"rs-6552255","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6552255","identity":"rs-6552255","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}