Abstract Body: Introduction: Restorative therapies have maximal impact when introduced early post-stroke. Dopamine modulates learning and plasticity, and its levels decrease after stroke, making it a key therapeutic candidate. For a restorative therapy to promote experience-dependent plasticity, concomitant training is needed and must be provided experimentally given low rehabilitation doses received with usual care (UC); here this was provided using an established telerehabilitation (TR) system. Current hypotheses: [H1] Adding intensive arm motor rehabilitation therapy to UC improves arm motor status more than UC alone, and [H2] Combining intensive arm motor therapy with levodopa further improves arm motor gains.
Methods: Adults ≤30 days post-stroke having moderate-severe arm weakness were randomized (3:3:2) to (1) 6 wk of intensive daily arm motor TR + daily carbidopa/levodopa (25/100) before therapy (given for first 3 wk), on top of UC; (2) TR + placebo before therapy (given for first 3 wk), on top of UC, or (3) UC alone. TR was initiated in the inpatient rehabilitation facility and completed at home. Assessments were blinded and included Action Research Arm Test (ARAT; primary endpoint) and Fugl-Meyer (FM; secondary endpoint) at baseline and 10 wk later.
Results: At baseline, subjects (n=25) were 13.2 days post-stroke, mean age 64.9 yr, ARAT 18.8, and FM 30.1. [H1] TR vs. UC: ARAT change from baseline to 10 wk later was 7.7 points higher in TR (23.8±2.8, n=16) vs. UC (16.1±3.2, n=9, propensity adjusted p=0.08). FM change was 12.3 points higher in TR (22.5±2.3) vs. UC (10.3±2.7, p=0.0027). [H2] TR+levodopa vs. TR+placebo vs. UC: ARAT change was not different between the 3 groups (p=0.17). However, FM change was: regression adjusted post hoc FM change with TR+levodopa (21.1±3.9) was significantly higher than change with UC (10.7±2.8, p=0.047), but FM change with TR+placebo (17.2±3.2) was not significantly higher than UC (p=0.103).
Conclusions: Therapeutic trials of patients ≤30 days post-stroke can be difficult to implement, e.g., due to transitions of care. This study describes a method to study a restorative drug tightly linked with intensive rehabilitation therapy using a telehealth approach. This pilot study, though at risk of type II error, provides evidence that adding intensive rehabilitation therapy to UC early post-stroke improves outcomes, and supports the potential value of adding levodopa to intensive rehabilitation therapy in the early post-stroke population.