Dose response of task-specific upper limb training in people at least 6 months poststroke: A phase II, single-blind, randomized, controlled trial

Abstract

Objective: The objectives of this work were to (1) determine whether higher doses of motor therapy in chronic poststroke hemiparesis result in better outcomes, compared to lower doses, and (2) evaluate potential modifiers of the dose-response relationship.

Methods: Eighty-five adults with upper extremity paresis ≥6 months poststroke were randomized to one of four dose groups in this single-blind, parallel, randomized, control trial. The dosing parameter manipulated was amount of task-specific training, as indexed by the number of task repetitions. Groups received 3,200, 6,400, 9,600, or individualized maximum (IM) repetitions, during 1-hour sessions, 4 days/week for 8 weeks. The intervention was an individualized, progressive, task-specific upper-limb training program designed to improve upper-limb functional motor capacity. The primary outcome was the slope of the Action Research Arm Test (ARAT) during the intervention. Effects of dose and potential modifiers of the dose-response relationship were evaluated with hierarchical linear models.

Results: ARAT scores for the 3,200, 9,600, and IM groups improved over time as indicated by slopes (ΔARAT/week, mean ± standard errors) of 0.40 ± 0.15, 0.31 ± 0.16, and 0.66 ± 0.14, respectively (p < 0.05). The slope of the 6,400 group was smaller (-0.05 ± 0.15) and significantly different from the 3,200 and IM groups (p < 0.001). Initial motor capacity, neglect, and other tested characteristics did not modify the dose-response relationship.

Interpretation: Overall, treatment effects were small. There was no evidence of a dose-response effect of task-specific training on functional capacity in people with long-standing upper-limb paresis poststroke. Ann Neurol 2016;80:342-354.

Figure 1

CONSORT diagram. *The analytic approach allowed inclusion of all participants with the first (baseline) and second (beginning of treatment week 2) assessments.

Figure 2

Individual (thin, dashed lines) and average (thick, solid lines) trajectories of upper limb functional capacity (Action Research Arm Test, ARAT). TW: treatment week, such that TW2 is the assessment taken at the beginning of the second treatment week. P1: post-intervention assessment. For the Individualized Maximum grp, the post-intervention assessment for most participants occurs between TW9 and TW15.