Neural Repair Therapies After Stroke: II. Principles for Clinical Trials

Stroke remains a leading cause of human disability worldwide. Additional approaches beyond acute stroke therapies are needed to improve patient outcomes. Neural repair therapies focus on promoting neural plasticity in surviving tissue rather than modifying the acute injury; examples include behavioral training, drugs, biological therapies, and neural stimulation. This review discusses principles related to patient selection, control group design, intervention timing, choice of outcome measures, experience-dependent plasticity, use of biomarkers, and statistical considerations, each of which emerges from a review of key stroke recovery trials. Patient selection strategies may benefit from incorporating neuroimaging and neurophysiology biomarkers to ensure viability of treatment targets. Modality-specific outcome measures offer advantages over global disability scales for repair-based trials. The timing of intervention is critical given evolving poststroke biology and the existence of critical periods for plasticity. Repair-based therapies benefit from pairing with concomitant experience of sufficient intensity and appropriate type to shape and reinforce brain circuits. Consideration of these key principles is expected to improve the design of trials that aim to promote neural repair and improve function after stroke. Researchers and clinicians should attend to these factors when designing and interpreting clinical trials to maximize the likelihood that neural repair therapies will improve disability after stroke.