Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB)
Condition: Cerebrovascular Stroke; Upper Extremity Paresis
MeSH terms: Stroke; Paresis
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Paired Vagus Nerve Stimulation; Rehabilitation
Intervention type(s): Device; Other
Intervention description(s): Stimulation of the vagus nerve that is paired with upper limb rehabilitation movements.; Rehabilitation movements to improve upper limb function after stroke
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double blind, randomized, parallel study with partial crossover (control subjects crossover to treatment after randomized portion)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment