Title: Clinical efficacy of functional strength training for upper limb motor recovery early after stroke: neural correlates and prognostic indicators
Funder: Department of Health (England)

Abstract: HYPOTHESIS: Functional Strength Training plus conventional physical therapy (FST+CPT) enhances upper limb motor recovery early after stroke more than CPT+CPT. AIMS: to determine: the relative efficacy of FST+CPT and CPT+CPT; the neural correlates of improvement in response to FST+CPT and CPT+CPT; whether any one or combination of baseline measures predict improvement in motor function in response to FST+CPT or CPT+CPT; and estimate of cost-effectiveness to inform a subsequent definitive clinical trial. DESIGN: randomized controlled observer-blind 2-group multi-centre efficacy trial with embedded explanatory measures. POPULATION: adults 14-60 days after stroke with upper limb paresis. INTERVENTIONS: protocol-driven CPT emphasises a therapist facilitating movement (therapist-dependent) whereas FST involves repetitive progressive resisted exercise during goal-directed functional activity (therapist-independent). All participants will receive the routine amount of CPT delivered by clinical therapists. Experimental FST and CPT will be delivered by different research therapists for 1.5 hours a day for 6 weeks. OUTCOMES: primary efficacy measure is change in the Action Research Arm Test (ARAT) from pre-treatment (baseline) to post-treatment (outcome). Explanatory measures include: voxel-wise estimates of brain activity during hand movement; brain white matter integrity (fractional anisotropy); and brain-muscle connectivity (e.g. latency of motor evoked potentials). ASSESSMENTS: will be conducted by an assessor blinded to group allocation at baseline outcome and at 6 months after stroke (follow-up). SAMPLE SIZE: is based on actual ARAT data from our previous early phase trial. A sample size of 129 per group would have 80% power to detect a clinically important difference of 6 points in ARAT change using a 2-sample t-test with a 5% 2-sided significance level. Anticipating an attrition rate of 10% at outcome a total of 288 participants will be randomized. ANALYSIS: will be conducted according to the intention-to-treat principle. The primary clinical efficacy analysis will compare continuous outcome variables between treatment groups using a normal multilevel model. Therapist will be included in the model as a zero-mean random effect. Effect of treatment will be summarised using the adjusted mean difference and 95% confidence interval. To identify the neural correlates of motor improvement in both groups we will investigate associations between change from baseline in clinical outcomes and each explanatory measure. We will adjust for the variables used in randomisation. Further exploration will use multilevel linear regression. We will investigate an extension of structural mean models/causal inference as a potential exploratory analysis. To determine whether baseline measurements predict improvement in motor function we will develop a multiple regression model. Principal components analysis will be used to reduce the dimensionality of the predictor variables. ECONOMIC BENEFIT: information on costs and effects will be used to give an indication of the likely cost-effectiveness of FST+CPT. TIMETABLE/RECRUITMENT RATE We anticipate recruiting 5 participants a month a centre for 20 months. Trial set-up needs 4 months follow-up 6 months and analysis - writeup 6 months.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE