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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. History of unilateral supratentorial ischemic stroke that occurred at least 9 months but not more than ten 10 years prior to enrollment.
  2. Age >22 years and <80 years.
  3. FMA-UE score of 20 to 50 (inclusive of 20 and 50).
  4. Ability to communicate, understand, and give appropriate consent. Subjects should be able to follow two-step commands.
  5. Right- or left-sided weakness of upper extremity.
  6. Active wrist flexion/extension; active abduction/extension of thumb and at least two additional digits.

Exclusion Criteria:

  1. History of hemorrhagic stroke
  2. Presence of ongoing dysphagia or aspiration difficulties.
  3. Subject receiving medication that may significantly interfere with the actions of VNS on neurotransmitter systems at study entry. A list of excluded medications will be provided to Investigators.
  4. Prior injury to vagus nerve, either bilateral or unilateral (e.g., injury during carotid endarterectomy).
  5. Severe or worse depression (Beck Depression Scale > 29) (Beck et al., 1961)
  6. Unfavorable candidacy for device implant surgery (e.g., history of adverse reactions to anesthetics, poor surgical candidate in surgeon's opinion, etc.)
  7. Current use of any other stimulation device, such as a pacemaker or other neurostimulator; current use of any other investigational device or drug.
  8. Medical or mental instability (diagnosis of personality disorder, psychosis, or substance abuse) that would prevent subject from meeting protocol timeline.
  9. Pregnancy or plans to become pregnant or to breastfeed during the study period.
  10. Current requirement, or likely future requirement, of diathermy during the study duration.
  11. Active rehabilitation within 4 weeks prior to consent.
  12. Botox injections or any other non-study active rehabilitation of the upper extremity within 4 weeks prior to therapy through the post-30 day visit (Visit 6).
  13. Severe spasticity of the upper limb (Modified Ashworth ≥3) (Bohannon and Smith, 1987).
  14. Significant sensory loss. Sensory loss will be measured using the Upper Extremity sensory section of the Fugl Meyer Assessment of Physical Performance. The assessment addresses light touch (2 items) and proprioception (4 items).The highest points attained is 12; subjects with scores less than 6 will be excluded from the study.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Michelle Lin, M.D., M.P.H.

Closed for enrollment

Contact information:

Rosita Almira

Almira.Rosita@mayo.edu

More information

Publications

  • Vagus nerve stimulation (VNS) paired with a motor task improves motor outcome in rat stroke models. It is hypothesised that VNS delivered during rehabilitation will improve upper limb function compared to control rehabilitation therapy. Two pilot clinical studies demonstrated acceptable safety and feasibility of VNS paired with rehabilitation for improved upper limb function after stroke. Participants who received rehabilitation paired with VNS demonstrated clinically meaningful improvements in motor function that exceed gains seen among controls who received similar rehabilitation without VNS. These preliminary data support a larger pivotal trial. Read More on PubMed
  • Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Read More on PubMed
  • Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20325246

Mayo Clinic Footer