Title: Feasibility and multi-centre clinical trial of gait rehabilitation in patients with recently diagnosed rheumatoid arthritis: the Gait Rehabilitation in Early Arthritis Trial [GREAT]
Funder: Chief Scientist Office, Scotland

Abstract: Design: Mixed methods feasibility phase and a pragmatic multi-centre 2-arm RCT with internal pilot phase, process evaluation and health economic evaluation. Setting: NHS hospital/community physiotherapy or podiatry clinics. Population: Adults with a diagnosis of RA with less than 2 years disease duration who have foot and/or ankle pain and/or synovitis. Inclusions: Diagnosis of RA; RA less than 2 years disease duration; aged 18+ years; willing to participate. Exclusions: Patients unable to complete the intervention as identified by their consultant rheumatologist or the recruiting clinician at screening; unable or unwilling to provide informed consent; currently taking part in other non-medical intervention studies targeting improved lower limb function and/or gait. Health technologies: In addition to usual care, participants will receive supervised gait rehabilitation comprising 2 to 6 1:1 treatment sessions over 12 weeks to guide participants for undertaking a gait rehabilitation circuit comprised of functional walking tasks. Intervention dose and progression will be individualised, and will include a supported home-based gait rehabilitation circuit and an embedded psychological component to promote positive behavioural change. Telephone-based sessions will be provided to maintain contact, promote adherence, and provide progression advice. The ingredients of the intervention have been adapted from existing programmes for improving balance, strength and walking ability in older adults and established RA. The intervention will be delivered by existing NHS physiotherapists or podiatrists. Comparator: Usual rheumatology medical management and referrals to physiotherapy and/or podiatry as required. All care received will be recorded. Outcomes and costs: The best performing primary outcome measure will be selected from evaluation of the responsiveness-to-change of 4 candidates in the feasibility phase: the Foot Function Index disability subscale, PROMIS physical function scale, ROAD lower extremity scale, and 10m walking speed. Secondary outcomes include: activities of daily living; health related-quality of life; exercise self-efficacy; physical activity. Healthcare resource use will be recorded. Outcomes will be collected at 3, 6 and 12 months from baseline by postal questionnaire. Sample size: To detect an effect size of 0.31 (mean difference 10, SD 32 on the FFIdis, 90% power, two-tailed significance of 5% and assuming 20% loss to follow-up, 550 participants will be recruited. Sample size will be checked upon completion of the internal pilot. Analysis: The primary (intention-to-treat) analysis will use a linear regression model of the primary outcome at 6 months, adjusted for baseline measurement of the primary outcome and all minimisation variables. Cost effectiveness and cost-utility analyses will be assessed using the primary outcome and the EQ-5D-5L from NHS and societal perspectives. Timetable: 60 months total project; set up 9 months; feasibility 12 months; internal pilot 9 months; main trial recruitment from 12-15 sites over 18 months; data collection over 24 months; analysis and report 3 months. Expertise in team: A multidisciplinary team comprising trialists, experts in rehabilitation research for RA, musculoskeletal pain and disability, rheumatology, physiotherapy, podiatry, psychology, statistics, health economics, mixed-methods and qualitative research and patient representatives.

Lay abstract: Background: Almost all patients with RA will develop foot and ankle pain and will experience difficulties with walking as a result. Patients walk slower and are more unsteady on their feet, and they often reduce their daily activities due to pain causing loss of muscle strength, balance and stability. During the first two years of RA, patients usually receive medications to control inflammation and may be referred to physiotherapy and/or podiatry for stretching/strengthening exercises and insoles. Whilst some patients improve, many continue to suffer from foot pain, walking difficulties and performing daily activities. Gait rehabilitation has been used with success in neurological conditions but its effectiveness in RA remains unknown. We have developed a new gait rehabilitation intervention for people with early RA which involves patients undertaking repetitions of walking tasks such as stepping over obstacles. This will be done under supervision by a physiotherapist or podiatrist initially, with support for completion of the walking tasks at home. We will evaluate whether adding this gait rehabilitation intervention to usual treatment results in any additional benefit compared to usual treatment alone in a randomised trial. Plan: First, we will conduct a feasibility study of 42 participants with early RA (within 2 years of diagnosis) to 1) identify the best way to measure the effectiveness of the gait rehabilitation intervention; 2) determine its acceptability and safety; and 3) determine whether it can be delivered as intended. Next, we will conduct a miniature version of the main trial to identify whether enough eligible patients can be recruited and kept in the study. Lastly, we plan a large trial to investigate whether gait rehabilitation adds benefits to usual care. Adults with early RA and foot and ankle pain who meet other criteria for inclusion will be invited to take part and asked to sign a consent form. Recruitment: Feasibility: We will recruit 42 participants over 6 months from 3 NHS Trusts/Health Board regions in Scotland and England. They will all receive usual care plus gait rehabilitation over 12 weeks. Trial: We will recruit 550 patients over 26 months from 12-15 NHS Trusts/Health Board regions in Scotland and England. Patients will be allocated by chance to one of two treatments: 1. Usual rheumatology care including physiotherapy and podiatry as required. 2. The same as in 1. plus gait rehabilitation, delivered over 2-6 sessions over 12 weeks and supplemented with a home programme. Method: Feasibility: We will measure intervention acceptability, adherence and safety after 12 weeks using postal questionnaires and interviews with a small subgroup of participants as well as clinicians who delivered the intervention. We will compare 4 measurement tools to determine the best tool to measure change in response to the intervention in the main trial. Trial: At 3, 6 and 12 months we will ask patients to complete and return postal questionnaires to find out about their walking ability/lower limb function, ability to do daily activities, their quality of life, their ability to undertake exercise and their levels of physical activity. We will also evaluate the amount of healthcare they have received to work out the costs of the new and usual care interventions in relation to any benefits achieved. This data will be used to establish whether or not gait rehabilitation should be offered to people with early RA in future.

Research activity codes: 6.7 PHYSICAL
Health categories: INFLAMMATORY AND IMMUNE SYSTEM