Cerebrovascular StrokeVNS-REHABNCT03131960
Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB)
A study testing Paired Vagus Nerve Stimulation and Rehabilitation in people with Cerebrovascular Stroke and Upper Extremity Paresis, run by MicroTransponder Inc. at 20 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 22 to 80 years
- Conditions the study is for
- Cerebrovascular Stroke, Upper Extremity Paresis
- What is being tested?
- Paired Vagus Nerve Stimulation and Rehabilitation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 1 Jul 2017to 30 Jun 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.)
Show all 14Show fewer
- 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.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States15 sites
Emory University Medical School
Atlanta, Georgia, 30329
Massachusetts General Hospital
Boston, Massachusetts, 02129
Medical University of South Carolina
Charleston, South Carolina, 29425
Ohio State University - Neuroscience Research Institute
Columbus, Ohio, 43210
UT Southwestern
Dallas, Texas, 75390
Rancho Research Institute
Downey, California, 90242
Spectrum Health
Grand Rapids, Michigan, 49503
TIRR Memorial Hermann (UT Health Science Center at Houston)
Houston, Texas, 77030
Mayo Jacksonville / Brooks Rehabilitation
Jacksonville, Florida, 32224
Vanderbilt University Medical Center
Nashville, Tennessee, 37240
New York Presbyterian Hospital / Weill Cornell Medicine
New York, New York, 10065
Thomas Jefferson
Philadelphia, Pennsylvania, 19107
Providence St. John's Medical Center
Santa Monica, California, 90404
Perseverance Research Center
Scottsdale, Arizona, 85254
Burke Medical Research Institute
White Plains, New York, 10605
United Kingdom5 sites
Royal Aberdeen Infirmary
Aberdeen, AB25 2ZB
University of Glasgow, Queen Elizabeth University Hospital
Glasgow, G51 4TF
Royal London
London, E15 4LZ
Newcastle (Royal Victoria Infirmary)
Newcastle upon Tyne, NE1 4LP
Royal Hallamshire Hospital
Sheffield, S1 4DA
About this study
Official title: A Pivotal Randomized Study Assessing Vagus Nerve Stimulation (VNS) During Rehabilitation for Improved Upper Limb Motor Function After Stroke (VNS-REHAB)
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.
Read the 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.
- Conditions
- Cerebrovascular Stroke, Upper Extremity Paresis
- Being tested
- Paired Vagus Nerve Stimulation, Rehabilitation
- Medical subject headings
- Stroke, Paresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paired Vagus Nerve StimulationDevice
Stimulation of the vagus nerve that is paired with upper limb rehabilitation movements.
RehabilitationOther
Rehabilitation movements to improve upper limb function after stroke
| Study group | Role | What they receive |
|---|---|---|
| VNS + Rehabilitation (1) | Experimental | Study treatment is vagus nerve stimulation (VNS) delivered during rehabilitation. Receives: Device: Paired Vagus Nerve Stimulation; Other: Rehabilitation |
| Control VNS | Active comparator | 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. Receives: Other: Rehabilitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: V5, One day after 6-weeks of therapy
Secondary outcomes (3)
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change
The Fugl-Meyer Assessment, Upper Limb (FMA-UE) was analyzed for change in average score at 90-days after 6-weeks of therapy (change in average FMA-UE from baseline [V4] to 90 days after therapy [V7]). 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).
Measured: V7, 90 days after 6-weeks of therapy
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Response
The Fugl-Meyer Assessment, Upper Limb (FMA-UE) Response is the percent of patients with a 6 point or greater improvement on the (FMA-UE). The percent of patients with the 6-point change is calculated at 90-days after 6-weeks of therapy compared to baseline (V4). 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).
Measured: V7, 90 days after 6-weeks of therapy
Wolf Motor Function Test (WMFT) Average Change
The Wolf Motor Function Test (WMFT) is an assessment scale of upper extremity functional level after stroke. The functional assessment range is an average of 15 sub-items with a range from 0 to 5, with 0 (meaning did not attempt) to 5 (meaning normal). WMFT 90-day - is a measure of the functional assessment change from baseline to 90 days after 6-weeks of therapy.
Measured: V7, 90 days after 6-weeks of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2017
- Study start1 Jul 2017
- Primary completion30 Apr 2020
- Study completion30 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Cerebrovascular StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind, randomized, parallel study with partial crossover (control subjects crossover to treatment after randomized portion)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- MicroTransponder Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ResearchPoint Global
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03131960
- Sponsor's protocol ID
- MT-St-03
- Acronym
- VNS-REHAB
- Status last verified
- Jul 2022
- First submitted
- 24 Apr 2017
- Last updated
- 20 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31903435Khodaparast 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.
PubMed 24553102Dawson 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.
PubMed 26645257Dawson 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.
PubMed 33894832Kimberley TJ, Vora I, Cramer SC, Wolf SL, Dawson J; VNS-REHAB Trial Group. Two-Year Retention of Benefits After Paired Vagus Nerve Stimulation in Stroke: Follow-Up of the VNS-REHAB Randomized Clinical Trial. Neurology. 2026 Aug 11;107(3):e218298. doi: 10.1212/WNL.0000000000218298. Epub 2026 Jul 14.
PubMed 42447422Kimberley 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.
PubMed 40329913Lin 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.
PubMed 38836606Vora 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.
PubMed 38815953
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pivotal Randomized Study Assessing Vagus Nerve Stimulation (VNS) During Rehabilitation for Improved Upper Limb Motor Function After Stroke (VNS-REHAB)
- ClinicalTrials.gov ID
- NCT03131960
- Acronym / sponsor ID
- VNS-REHAB / MT-St-03
- Conditions
- Cerebrovascular Stroke, Upper Extremity Paresis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- MicroTransponder Inc.Industry (pharma, biotech, devices)
- Collaborators
- ResearchPoint Global
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 30 Apr 2020 (actual)
- Study completion
- 30 Jun 2022 (actual)
- First posted
- 27 Apr 2017 (actual)
- Results
- Posted 14 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blind, randomized, parallel study with partial crossover (control subjects crossover to treatment after randomized portion)
| Arm | Type | Receives |
|---|---|---|
| VNS + Rehabilitation (1) | Experimental | Device: Paired Vagus Nerve Stimulation, Other: RehabilitationStudy treatment is vagus nerve stimulation (VNS) delivered during rehabilitation. |
| Control VNS | Active comparator | Other: RehabilitationActive 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. |
Who may qualify
- Ages
- 22 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paired Vagus Nerve StimulationStimulation of the vagus nerve that is paired with upper limb rehabilitation movements. | Device | VNS + Rehabilitation (1) |
| RehabilitationRehabilitation movements to improve upper limb function after stroke | Other | Control VNS, VNS + Rehabilitation (1) |
Primary outcome
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change
Time frame: V5, One day after 6-weeks of therapy
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).
3 secondary outcomes
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change
Time frame: V7, 90 days after 6-weeks of therapy
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Response
Time frame: V7, 90 days after 6-weeks of therapy
Wolf Motor Function Test (WMFT) Average Change
Time frame: V7, 90 days after 6-weeks of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31903435Kimberley 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.
- Background: PubMed 24553102Khodaparast 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.
- Background: PubMed 26645257Dawson 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.
- Results publication: PubMed 33894832Dawson 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.
- Derived from this study: PubMed 42447422Kimberley TJ, Vora I, Cramer SC, Wolf SL, Dawson J; VNS-REHAB Trial Group. Two-Year Retention of Benefits After Paired Vagus Nerve Stimulation in Stroke: Follow-Up of the VNS-REHAB Randomized Clinical Trial. Neurology. 2026 Aug 11;107(3):e218298. doi: 10.1212/WNL.0000000000218298. Epub 2026 Jul 14.
- Derived from this study: PubMed 40329913Kimberley 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.
- Derived from this study: PubMed 38836606Lin 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.
- Derived from this study: PubMed 38815953Vora 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.
- Study recruiting websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Paired Vagus Nerve Stimulation and Rehabilitation in people with Cerebrovascular Stroke and Upper Extremity Paresis, run by MicroTransponder Inc. at 20 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change (time frame: V5, One day after 6-weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03131960, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022.