Abstract
BACKGROUND: Stroke remains the leading cause of long-term disability worldwide. Approximately 60% of individuals with chronic ischemic stroke experience persistent upper limb impairment that limits daily activities. The Repair Study aims to evaluate the safety and efficacy of vagus nerve stimulation (VNS) paired with rehabilitation in patients with chronic ischemic stroke in developing countries, including those with severe upper limb dysfunction, thereby generating evidence to support broader global application. METHODS: It is a multicenter, triple-blinded, randomized controlled trial conducted across 13 centers in China. Up to 99 participants with upper limb motor impairment, 9 months to 10 years post-stroke, will be enrolled. All participants will undergo VNS implantation (Model G115R/G115, PINS Medical, Beijing, China) and be randomized 2:1 by a central randomization system to active stimulation (0.8 mA) or sham stimulation (0 mA) paired with standardized upper limb rehabilitation. The blinded phase includes 6 weeks of clinical therapy (three sessions/week, 90-120 min/session, ≥300 stimulation-movement repetitions) followed by 6 weeks of home-based therapy (30 min/day). Post-unblinding, the active VNS group continues home-based therapy, while the sham group receives 6 weeks of clinic-based therapy. DISCUSSION: The primary outcome is the between-group difference in Fugl-Meyer Assessment for Upper Extremity scores at the end of 6 weeks of clinical therapy. Secondary outcomes include additional motor, functional, and quality-of-life measures. Safety will be assessed through adverse event monitoring. The Repair Study is a multicenter randomized controlled trial targeting chronic ischemic stroke populations in developing countries. It supplements the existing clinical evidence by enrolling patients with more servere motor dysfunction and being conducted in a developing country. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06722677.