Differentiating Challenges for Recruitment and Enrollment into Vagus Nerve Stimulation Studies for Individuals with Chronic Ischemic Stroke and Spinal Cord Injury

Research Objectives: Vagus nerve stimulation (VNS) paired with rehabilitation is a promising intervention for improving recovery of upper limb function after chronic stroke and spinal cord injury (SCI). Our objective was to discuss the feasibility of recruiting and enrolling participants with chronic ischemic stroke and SCI into clinical trials investigating an implanted VNS device.

Design: Two simultaneous prospective, double-blind, sham-controlled, plus open-label extension clinical trials

Setting: Community Setting

Participants: Individuals with medical clearance for surgery and feasible availability to attend study visits with chronic (> 1 year) ischemic stroke [ages 22-79, Upper Extremity Fugl-Meyer (UEFM) score 20-50] or incomplete traumatic cervical SCI (ages 18-64, ASIA Impairment Score of B, C, D with residual upper limb motor deficits) were eligible to participate in this clinical trial.

Interventions: Between September 2021 through April 2024 (stroke=20) and February 2021 through January 2024 (SCI=20), participants were recruited and enrolled into the diagnosis appropriate clinical trial.

Main Outcome Measures: Sources of recruitment, screen failure rate, reasons for screen failure, participants decline rate, reasons for decline, enrollment rate, implantation rate, and study completion rate were recorded.

Results: 1944 participants (stroke=1408, SCI=536) were identified from 27 recruitment sources (stroke=13, SCI=14). Primary sources of recruitment were a research recruitment service (stroke=1199, SCI=393), social media (stroke=71, SCI=22), and previous patient databases (stroke=53, SCI=35). 1018 participants (stroke=694, SCI=324) failed initial screening efforts primarily due to not meeting UEFM score (stroke=253) and incomplete SCI (SCI=111) requirements. After initial screening, 276 participants (stroke=229, SCI=47) declined the study, largely due to disinterest (stroke=127, SCI=25) and surgery concerns (stroke=61, SCI=3). 68 participants were enrolled (stroke=37, SCI=31), 38 were implanted (stroke=19, SCI=19), and 36 (stroke=17, SCI=19) completed the trials. The most successful recruitment sources were the research recruitment service (stroke=37%) and word-of-mouth (stroke=32%, SCI=74%). Overall, 89% of participants with stroke and 100% of participants with SCI who received the implanted VNS device completed the study.

Conclusions: Recruiting and enrolling participants with chronic stroke and SCI into clinical trials investigating an implantable VNS device is feasible but presents with challenges related to a high screen out rate. Inquiries necessary to successfully recruit for the stroke trial was double the SCI trial, possibly due to more stringent upper extremity movement inclusion criteria. However, participants who underwent implantation of the VNS device had a high study completion rate. To streamline recruitment, future trials could consider expanding eligibility criteria and enrolling across multiple locations.

Author(s) Disclosures: DARPA (N66001-17-2-4011) and NINDS (UH3NS109497) funding received for these studies.