Title: RATULS: Robot Assisted Training for the Upper Limb after Stroke
Funder: Department of Health and Social Care

Abstract: Design: A pragmatic multicentre randomised controlled trial; cost analysis; and process evaluation. Setting: Sixteen NHS stroke services will recruit participants from stroke units, hospital and community rehabilitation services, and primary care registers. Four stroke services where a MIT-Manus robotic gym system is based will act as study 'hubs' and provide all robot assisted training. Three stroke services adjacent to each hub will be study ‘spokes' and provide enhanced therapy and usual care. Target Population: Adults at least one week post stroke with moderate to severe upper limb functional limitation (Action Research Arm Test score 0-39 (0=no function and 57=full arm function) who can comply with the trial protocol will be invited to participate. Patients with both acute and chronic stroke will be recruited to reflect how robot assisted training will be used within the NHS if it is clinically effective and affordable. Health Technologies Being Assessed: A 3 arm efficacy trial will be conducted. Group 1 will receive robot assisted training using the MIT-Manus robotic gym system. Group 2 will receive an enhanced upper limb therapy programme based upon current evidence based practice and national guidelines. The robot assisted training and enhanced upper limb therapy will be provided for up to 45 minutes per day, 3 days per week for 12 weeks, in addition to usual care. Randomisation: Individual participant randomisation stratified by centre, time since stroke and severity of upper limb impairment via an independent randomisation service. Measurement of Outcomes: Outcomes will be measured at 3 and 6 months post randomisation. The primary outcome will be the Action Research Arm Test (ARAT) which consists of 19 functional movement tasks which are divided into 4 domains (grasp, grip, pinch and gross movement). Outcome assessments will undertaken by a research therapist who is blinded to the randomisation group. Sample Size: The study will be powered to detect a 15% difference in ‘successful outcome’ between each of the 3 pairs of treatments (robot assisted training, enhanced upper limb therapy, usual care) at 3 months (power=80% and significance level of 1.67% because of multiple comparisons). Allowing for 10% drop out this will require a sample size of 720 participants (240 participants per arm). Patients with severe initial upper limb impairment are likely to improve less than those with moderate impairment. ‘Successful outcome’ is defined as: baseline ARAT 0-7 must improve by 3 or more points; ARAT 8-13 improve by 4 or more points; ARAT 14-19 improve by 5 or more points; ARAT 20-39 improve by 6 or more points. Measurement of costs: Data collection from the trial will focus on estimating the cost of the interventions, the use of secondary and primary care, and the costs to patients and their families. The perspective of the costing analysis will be the NHS and patient. Secondary care resource use, primary care resource use and patient costs will be obtained from patient completed questionnaires at 6 months post randomisation. Unit costs will be based on nationally available data and study-specific estimates. An economic model will also be developed to assess the longer terms costs. We will extrapolate from the end of the trial follow up period over the remainder of the participant's life to identify the cost implications of differences in disability. The study will also provide information on both costs and outcomes sufficient for a within trial and model based cost-utility analysis. Qualitative study: Alongside the RCT, a process evaluation will be conducted to understand (i) patients' and health service professionals' experiences of robot assisted training; enhanced upper limb therapy and usual care (ii) factors affecting the implementation of the trial within and across study sites. Semi-structured interviews (n= approx. 100-120 during the project) will be conducted across study sites with maximum variation sampling of patients receiving the interventions and health service professionals involved in their delivery, at appropriate time points across the conduct of the trial (utilising repeat interviews as appropriate). Qualitative analysis will use the constant comparative technique.

Lay abstract: Loss of arm function is a distressing and common consequence of stroke. Currently it is unclear how best to provide therapy to improve arm recovery. Research suggests that robot assisted therapy may be beneficial but this is not proven and further research is needed to establish if this treatment is effective and cost effective. This clinical trial aims to evaluate whether the MIT-Manus robotic gym system can improve arm function after stroke. MIT-Manus is the international market leader in upper limb robot assisted rehabilitation and its development is supported by high quality research. Four of 11 studies in a Cochrane review of robot assisted arm training after stroke evaluated MIT-Manus and a further study was published in the New England Journal of Medicine in 2010. MIT-Manus has continued to develop in terms of size, mobility and ease of use over the last 10 years. It can now be used for shoulder, elbow, wrist and hand rehabilitation – a gym for the upper extremity. Patients sit at a table and place their affected arm onto the MIT-Manus arm support and attempt to move their arm to play a game on the MIT-Manus computer screen. Movements are assisted by MIT-Manus if the patient cannot perform the movement themselves. Research suggests that interactive repetitive task practice is key to improving arm function following stroke which is a key feature of MIT-Manus. Treatment with the robot will be compared to treatment with i) an enhanced upper limb therapy programme delivered by a therapist and ii) usual post stroke rehabilitation. Stroke patients with reduced arm function who wish to take part in the trial will be randomly assigned treatment with either the robot, or enhanced therapy treatment with a therapist or usual care. The robot assisted training and the enhanced upper limb therapy with a therapist will be delivered for 45 minutes, 3 times per week for 12 weeks, in addition to usual care. The trial aims to recruit 720 participants from 16 NHS stroke services. The 16 stroke services will be organised as 'hubs' and 'spokes'. There will be 4 hubs which have a MIT-Manus robotic gym system and each hub will work will 3 adjacent spokes. Study participants receiving robot assisted training will travel to their local hub for treatment. Participants receiving enhanced upper limb therapy or usual care will be treated at their local stroke service which may be a hub or a spoke. To assess whether the treatments are beneficial, study participants will be asked to answer questions about what activities they can and cannot do with their affected arm and undertake various simple tasks supervised by a research therapist before they enter the trial and then again at 3 and 6 months post randomisation. They will also be asked to complete a questionnaire about the impact that the stroke has had upon their lives. The scores from the measurements will be compared to determine if robot assisted training helps improve a patients arm function and recovery, and improves quality of life after stroke. The trial will also evaluate the cost effectiveness of the robot. A small number of participants and rehabilitation staff will be invited to take part in face to face interviews where a researcher will ask about their views and experience of the trial treatments.

Research activity codes: 6.3 MEDICAL DEVICES;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL;STROKE