Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB)
VNS-REHAB
A Pivotal Randomized Study Assessing Vagus Nerve Stimulation (VNS) During Rehabilitation for Improved Upper Limb Motor Function After Stroke (VNS-REHAB)
1 other identifier
interventional
108
2 countries
20
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Jul 2017
Longer than P75 for not_applicable
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2017
CompletedFirst Posted
Study publicly available on registry
April 27, 2017
CompletedStudy Start
First participant enrolled
July 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2020
CompletedResults Posted
Study results publicly available
June 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2022
CompletedJuly 20, 2022
July 1, 2022
2.8 years
April 24, 2017
April 27, 2021
July 11, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change
The Fugl-Meyer Assessment, Upper Limb (FMA-UE) was analyzed for difference in average change at 1-day after 6-weeks of therapy compared to baseline (Difference in average change in FM-A from baseline \[V4\] to one day after therapy \[V5\]). The upper extremity portion of the Fugl-Meyer Assessment (FMA-UE) was collected at each visit. The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment).
V5, One day after 6-weeks of therapy
Secondary Outcomes (3)
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change
V7, 90 days after 6-weeks of therapy
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Response
V7, 90 days after 6-weeks of therapy
Wolf Motor Function Test (WMFT) Average Change
V7, 90 days after 6-weeks of therapy
Study Arms (2)
VNS + Rehabilitation (1)
EXPERIMENTALStudy treatment is vagus nerve stimulation (VNS) delivered during rehabilitation.
Control VNS
ACTIVE COMPARATORActive 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.
Interventions
Stimulation of the vagus nerve that is paired with upper limb rehabilitation movements.
Rehabilitation movements to improve upper limb function after stroke
Eligibility Criteria
You may qualify if:
- History of unilateral supratentorial ischemic stroke that occurred at least 9 months but not more than ten 10 years prior to enrollment.
- Age \>22 years and \<80 years.
- FMA-UE score of 20 to 50 (inclusive of 20 and 50).
- Ability to communicate, understand, and give appropriate consent. Subjects should be able to follow two-step commands.
- Right- or left-sided weakness of upper extremity.
- Active wrist flexion/extension; active abduction/extension of thumb and at least two additional digits.
You may not qualify if:
- History of hemorrhagic stroke
- Presence of ongoing dysphagia or aspiration difficulties.
- 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.
- Prior injury to vagus nerve, either bilateral or unilateral (e.g., injury during carotid endarterectomy).
- Severe or worse depression (Beck Depression Scale \> 29) (Beck et al., 1961)
- Unfavorable candidacy for device implant surgery (e.g., history of adverse reactions to anesthetics, poor surgical candidate in surgeon's opinion, etc.)
- Current use of any other stimulation device, such as a pacemaker or other neurostimulator; current use of any other investigational device or drug.
- Medical or mental instability (diagnosis of personality disorder, psychosis, or substance abuse) that would prevent subject from meeting protocol timeline.
- Pregnancy or plans to become pregnant or to breastfeed during the study period.
- Current requirement, or likely future requirement, of diathermy during the study duration.
- Active rehabilitation within 4 weeks prior to consent.
- 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).
- Severe spasticity of the upper limb (Modified Ashworth ≥3) (Bohannon and Smith, 1987).
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MicroTransponder Inc.lead
- ResearchPoint Globalcollaborator
Study Sites (20)
Perseverance Research Center
Scottsdale, Arizona, 85254, United States
Rancho Research Institute
Downey, California, 90242, United States
Providence St. John's Medical Center
Santa Monica, California, 90404, United States
Mayo Jacksonville / Brooks Rehabilitation
Jacksonville, Florida, 32224, United States
Emory University Medical School
Atlanta, Georgia, 30329, United States
Massachusetts General Hospital
Boston, Massachusetts, 02129, United States
Spectrum Health
Grand Rapids, Michigan, 49503, United States
New York Presbyterian Hospital / Weill Cornell Medicine
New York, New York, 10065, United States
Burke Medical Research Institute
White Plains, New York, 10605, United States
Ohio State University - Neuroscience Research Institute
Columbus, Ohio, 43210, United States
Thomas Jefferson
Philadelphia, Pennsylvania, 19107, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37240, United States
UT Southwestern
Dallas, Texas, 75390, United States
TIRR Memorial Hermann (UT Health Science Center at Houston)
Houston, Texas, 77030, United States
Royal Aberdeen Infirmary
Aberdeen, AB25 2ZB, United Kingdom
University of Glasgow, Queen Elizabeth University Hospital
Glasgow, G51 4TF, United Kingdom
Royal London
London, E15 4LZ, United Kingdom
Newcastle (Royal Victoria Infirmary)
Newcastle upon Tyne, NE1 4LP, United Kingdom
Royal Hallamshire Hospital
Sheffield, S1 4DA, United Kingdom
Related Publications (7)
Kimberley TJ, Prudente CN, Engineer ND, Pierce D, Tarver B, Cramer SC, Dickie DA, Dawson J. Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. Eur Stroke J. 2019 Dec;4(4):363-377. doi: 10.1177/2396987319855306. Epub 2019 Jun 17.
PMID: 31903435BACKGROUNDKhodaparast N, Hays SA, Sloan AM, Fayyaz T, Hulsey DR, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabil Neural Repair. 2014 Sep;28(7):698-706. doi: 10.1177/1545968314521006. Epub 2014 Feb 18.
PMID: 24553102BACKGROUNDDawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, Engineer N. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016 Jan;47(1):143-50. doi: 10.1161/STROKEAHA.115.010477. Epub 2015 Dec 8.
PMID: 26645257BACKGROUNDDawson J, Liu CY, Francisco GE, Cramer SC, Wolf SL, Dixit A, Alexander J, Ali R, Brown BL, Feng W, DeMark L, Hochberg LR, Kautz SA, Majid A, O'Dell MW, Pierce D, Prudente CN, Redgrave J, Turner DL, Engineer ND, Kimberley TJ. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. 2021 Apr 24;397(10284):1545-1553. doi: 10.1016/S0140-6736(21)00475-X.
PMID: 33894832RESULTKimberley TJ, Cramer SC, Wolf SL, Liu C, Gochyyev P, Dawson J; VNS-REHAB Trial Group. Long-Term Outcomes of Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation After Stroke. Stroke. 2025 Aug;56(8):2255-2265. doi: 10.1161/STROKEAHA.124.050479. Epub 2025 May 7.
PMID: 40329913DERIVEDLin S, Rodriguez CO, Wolf SL. Vagus Nerve Stimulation Paired With Upper Extremity Rehabilitation for Chronic Ischemic Stroke: Contribution of Dosage Parameters. Neurorehabil Neural Repair. 2024 Aug;38(8):607-615. doi: 10.1177/15459683241258769. Epub 2024 Jun 5.
PMID: 38836606DERIVEDVora I, Gochyyev P, Engineer N, Wolf SL, Kimberley TJ. Distal Versus Proximal Arm Improvement After Paired Vagus Nerve Stimulation Therapy After Chronic Stroke. Arch Phys Med Rehabil. 2024 Sep;105(9):1709-1717. doi: 10.1016/j.apmr.2024.05.018. Epub 2024 May 28.
PMID: 38815953DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- MicroTransponder Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participants, therapists (care providers), investigators, and outcomes assessors do not know which group (VNS or control VNS) the patients are randomized. Only one person at the site - the programmer who programs the device settings - knows which group the subject is randomized into.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2017
First Posted
April 27, 2017
Study Start
July 1, 2017
Primary Completion
April 30, 2020
Study Completion
June 30, 2022
Last Updated
July 20, 2022
Results First Posted
June 14, 2021
Record last verified: 2022-07
Data Sharing
- IPD Sharing
- Will not share