Dosage Matters

Abstract

Background and Purpose- For stroke rehabilitation, task-specific training in animal models and human rehabilitation trials is considered important to modulate neuroplasticity, promote motor learning, and functional recovery. Little is known about what constitutes an effective dosage of therapy. Methods- This is a parallel group, 4 arms, single-blind, phase IIb, randomized controlled trial of 4 dosages of arm therapy delivered in an outpatient setting chronically after stroke. Participants were randomized into groups that varied in duration of scheduled therapy (ie, 0, 15, 30, or 60 hours). Forty-one participants completed the study. Planned primary analyses used linear mixed effects regression to model changes from baseline to postintervention in the Motor Activity Log-Quality of Movement rating and the Wolf Motor Function Test time score over 3 weeks of training as a function of therapy dosage. Results- We observed a dose response for the Motor Activity Log-Quality of Movement: the model that included dose and dose by week interaction significantly better fit the data than the model that included week only (log-likelihood test, P=0.0026). In addition, the greater the dosage of training, the greater the change in Motor Activity Log-Quality of Movement, with the dose by week interaction parameter equal to 0.0045 ( P=0.0016; 95% CI, 0.0018-0.0071). Over the 3 weeks of therapy, there was a gain of 0.92 in Motor Activity Log-Quality of Movement for the 60-hour group compared to the 0-hour group. There was no dose response for the Wolf Motor Function Test. Conclusions- For mild-to-moderately impaired stroke survivors, the dosage of patient-centered, task-specific practice systematically influences the gain in quality of arm use but not functional capacity. We caution that we may have been underpowered for the functional capacity outcome. These findings highlight the importance of recovery outcomes that capture arm use in the natural environment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01749358.

Keywords: motor activity; movement; patient preference; rehabilitation; survivors.

Figure 1.

Timeline of train-wait-train training and testing. The total study time is 9 mo and 3 wk. The Ts show 14 tests. Importantly, the gray Ts show the tests used here. The first 2 Ts represent the baseline tests (test 1 and 2). The filled rectangles labeled 1, 2, and 3 show the three 1-week bouts of training. For each week of training, a test was given in the morning of the first day and 3 days after training ended. Each of the 3 training weeks was separated by 4 wk (wait periods). The 4 groups receive different number of training hours within each week. All tests included Motor Activity Log-Quality of Movement and Wolf Motor Function Test. Patients also underwent a structural research grade magnetic resonance imaging within one month of enrollment.

Figure 2.

Individual participant plots showing Motor Activity Log-Quality of Movement (MAL_Q) change by week. Each row illustrates group data and model fit for blue=0, red=15, black=30, and green=60 h. ID numbers correspond to a participant. Individual participant data (dot) and superimposed continuous dose mixed effect model (lines). Participant data were recorded before the start of the intervention period and after each training week or active control. A single mixed model was plotted for all dosages and participants.

Figure 3.

Change in Motor Activity Log-Quality of Movement (MAL_Q) over the intervention period as a function of dosage. The line shows the significant dose-response curve (P=0.0016) derived from the continuous model. The error bars show the estimated slopes (marginal means) and 95% CIs for each dosage from the categorical model.