Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke.
Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation.
Setting: NHS stroke services.
Participants: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation.
1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks
2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks
3. Usual NHS care in accordance with local clinical practice
Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment.
Primary outcome: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation.
Secondary outcomes: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months.
Blinding: outcomes are undertaken by blinded assessors.
Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes.
Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial.
Sample size: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0–7 must improve by 3 or more points; baseline ARAT 8–13 improve by 4 or more points; baseline ARAT 14–19 improve by 5 or more points; baseline ARAT 20–39 improve by 6 or more points.
The results from this trial will determine whether robot-assisted training improves upper limb function post stroke.
Stroke is the commonest cause of complex adult disability in high-income countries . Loss of arm function affects 69% of people who have a stroke . Only 12% of people with arm weakness at the onset of stroke make a full recovery . Improving arm function has been identified as a research priority by stroke survivors, carers and health professionals who report that current rehabilitation pays insufficient attention to arm recovery .
Robot-assisted training enables a greater number of repetitive tasks to be practised in a consistent and controllable manner. Repetitive task training is known to drive Hebbian plasticity, where wiring of pathways that are coincidently active is strengthened [5, 6]. A dose of greater than 20 h of repetitive task training improves upper limb motor recovery following a stroke  and, therefore, robot-assisted training has the potential to improve arm motor recovery after stroke. We anticipate that Hebbian neuroplasticity, which is learning dependent, will operate regardless of the post-stroke phase.
A Cochrane systematic review of electromechanical and robot-assisted arm training after stroke reported outcomes from a total of 1160 patients who participated in 34 randomised controlled trials (RCTs). Improvements in arm function (standardised mean difference (SMD) 0.35, 95% confidence interval (CI), 0.18–0.51) and activities of daily living (SMD 0.37, 95% CI, 0.11–0.64) were found in patients who received this treatment, but studies were often of low quality . In the UK there is currently insufficient evidence to justify the use of this technology in routine clinical practice.
In addition, studies which suggest that robot-assisted training may improve upper limb function after stroke should be treated with caution as participants who were randomised to receive robot-assisted training may have also received an increased intensity of rehabilitation sessions (e.g. frequency or duration) compared to participants in the control groups. Greater intensity of upper limb rehabilitation sessions has been shown to improve upper limb functional outcomes , and a meta-analysis of robot-assisted training RCTs reported that if control group therapy sessions were delivered at the same frequency and duration, there was no additional functional improvement . Studies are required which provide further direct evidence of the effectiveness of robot-assisted training without the confounding effect of therapy dose.
The aim of the Robot Assisted Training for the Upper Limb after Stroke (RATULS) trial is to evaluate the clinical and cost-effectiveness of robot-assisted training compared to an upper limb therapy programme of the same frequency and duration, and usual post-stroke care.
The null hypothesis is that there is no difference in upper limb function at 3 months between study participants who receive robot-assisted training and those who receive an enhanced upper limb therapy programme and those who receive usual post-stroke care. The RATULS trial will be making comparisons of the effectiveness of rehabilitation on upper limb function between all three pairs of trial arms.