The effects of individually tailored rTMS on hand function in chronic stroke: a protocol for an adaptive, phase II, randomized, sham-controlled clinical trial

Abstract

Stroke is a leading cause of disability among adults. Existing rehabilitation programs haven’t been able to accomplish full motor recovery partially due to the pathologic plasticity exerted from the unaffected hemisphere to the affected one. This inhibition can be disrupted using non-invasive brain stimulation (NIBS). Transcranial magnetic stimulation (TMS) is a NIBS technique that has the capacity of depolarizing or hyperpolarizing neurons depending on the frequency of the pulses. Although several trials have been conducted to find the efficacy of low frequency rTMS for motor recovery after stroke, their results have been heterogeneous. One of the main variables that determine the response to rTMS is the dose, corresponding to the number of pulses delivered to the patients. However, due to the localization and the extension of the stroke, each patient responds differently to certain dose. Therefore, using the SPIRIT statement, we designed a protocol for an adaptive, phase II, randomized, sham-controlled clinical trial. The study proposed will include 75 patients between 45 and 80 years old, with hand function impairment after 1 to 3 years of stroke; it will exclude patients with severe cognitive or neuropsychiatric comorbilities, any previous stroke episode, Fugl Meyer (Upper limb) < 20, inability to understand the task or contraindications for rTMS. The study will have 3 arms: individually tailored (adaptive dosing) low frequency (1Hz) rTMS plus standard of care rehabilitation (physical therapy) compared to sham and fixed rTMS plus standard of care rehabilitation. The intervention will be applied during 6 weeks after which the main analysis will be performed. Subjects will be followed-up during 3 months and the results from this analysis will be exploratory. This protocol will use the results from the Pegboard test as a primary outcome and SF-36 questionnaire, hand strength, and responder´s rate as secondary outcomes.