Dosage Matters: A Randomized Controlled Trial of Rehabilitation Dose in the Chronic Phase after Stroke

Abstract

Background and PurposeFor stroke rehabilitation, task-specific training in animal models and human rehabilitation trials is considered important to trigger inherent neuroplasticity, promote motor learning, and functional recovery. Little is known, however, about what constitutes an effective dosage of therapy.\n\nMethodsThis is a parallel group, four arm, single blind, phase I, randomized control trial of four dosages of upper extremity therapy delivered in an outpatient setting during the chronic phase after stroke. Participants were randomized into groups that varied in total dosage of therapy (i.e., 0, 15, 30, or 60 hours). Seven hundred and four participants were assessed for eligibility, 50 were eligible to enroll, 45 were randomized, 44 participated and 41 completed the study. Planned primary analyses used linear mixed effects regression to model baseline to post-intervention changes in the Motor Activity Log-Quality of Movement rating (MALQ) and the Wolf Motor Function Test (WMFT) time score as a function of therapy dosage. A series of hierarchical models were constructed using the MALQ and WMFT.\n\nResultsWe observed a significant dose response curve: the greater the dosage of training, the greater the change in MALQ, with the dose by week slope parameter of 0.0045 ({Delta}MAL/hour/week; p = 0.0011; 95% CI = [0.0019; 0.0071]). Over the 3 weeks of therapy, this corresponds to a gain of 0.81 in MALQ for the 60 hour dose.\n\nConclusionsFor mild-to-moderately impaired stroke survivors, the dosage of a patient-centered, task specific motor therapy was shown to systematically influence the gain in quality of arm use in the natural environment, but not functional capacity as measured in the laboratory. We highlight the importance of recovery outcomes that capture arm use vs. functional capacity.\n\nClinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT 01749358