Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB)

Cerebrovascular Stroke, Upper Extremity Paresis

This is a pivotal phase study of up to 120 subjects and 15 clinical sites. All subjects are implanted with the Vivistim System® and then randomized to either study treatment or active-control treatment. The randomization will be stratified by age (\<30, \>30) and baseline FMA UE (20 to \<35; \>35 to 50). Study treatment is vagus nerve stimulation (VNS) delivered during rehabilitation. Active control treatment is rehabilitation (standard-of-care treatment) with only a minimal amount of VNS at the start of each session intended to support blinding.

This study has three distinct stages: Stage I, an acute blinded stage, Stage II, an unblinded stage through one year of standard VNS, and Stage III, an unblinded stage for yearly follow-up after one year of VNS. The Control group crosses over to VNS treatment at Stage II. For Stage I, subjects have: * consent and evaluation (screening), * one pre-implant evaluation, * surgical implant of the device system and randomization into one of the treatment arms, * one baseline evaluation after device implant surgery but before initiation of treatment, * 6 weeks of treatment (standard-of-care rehabilitation + standard VNS or standard-of-care rehabilitation + active control VNS), and then * post-acute therapy evaluations at 1, 30 and 90 days after the 6 weeks of treatment. * Between Day 1 (V5) and Day 30 (V6) post-acute therapy, both groups will receive in-home, self-directed rehabilitation (30 minutes of daily rehabilitation as assigned by the therapist) with either in-home activated VNS (VNS group) or no VNS (Control group). This means that the control subjects will not have the in-home activated VNS until they complete the second 6-week session of in-clinic rehabilitation with follow-up assessments as described below in Stage II. At this point (Day 30) subjects start scheduling for their continuing long-term follow-up. * Between Day 30 and Day 90 post-acute therapy, both groups continue in-home, self-directed rehabilitation (30 minutes of daily rehabilitation as assigned by the therapist). The VNS group continues to receive in-home VNS with magnet use; the Control group continues to use the magnet but does not receive any VNS. The Day 90 post-acute therapy visit is V7; it is the first quarterly visit (3 months after study therapy) for the VNS group and is the re-baseline visit (visit just prior to the initiation of standard VNS therapy) for the Control group. Stage II: * VNS subjects will continue to have quarterly assessments through the end of the first year (6m, 9m, 12m). * Subjects in the control group will crossover for a second 6-week in-clinic rehabilitation period where they will now receive rehabilitation with standard VNS. * Control subjects will then have the three post therapy assessments (1, 30 and 90 days after therapy ends); in-home VNS initiated by a magnet swipe starts at the Post-1 visit (LT1). Thereafter, control subjects will follow the same schedule as VNS subjects for the remainder of the study (6m, 9m, 12m follow-ups, plus yearly visits thereafter). * Subjects in both groups will receive booster in-clinic rehabilitation plus VNS therapy sessions one month prior to their 6- and 12-month assessment visits. These sessions occur on three days over a one-week period (typically Mon, Wed, Fri). Stage III: • After one year of standard VNS therapy (\ 13.5 months after implant for VNS group subjects and \ 18 months after implant for Control group subjects), subjects who wish to keep their device for further use will have annual follow-up assessments until commercial approval.

United Kingdom, United States

Participants by arm

Withdrawals & dropouts