Spinal Cord Injury (SCI)NCT07689227
Closed-Loop Vagus Nerve Stimulation (CLV) for Recovery of Gait After Spinal Cord Injury (SCI)
A study testing CLV in people with Spinal Cord Injury (SCI) and Gait, run by The University of Texas at Dallas at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, feasibility, and preliminary effectiveness of the ReWire system, which delivers vagus nerve stimulation (VNS) paired with lower limb rehabilitation to improve gait in individuals with mobility impairments resulting from chronic, incomplete spinal cord injury (SCI). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Spinal Cord Injury (SCI), Gait, Reduced Physical Activity
- What is being tested?
- CLV
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Sep 2026to Dec 2028
- Phase
- Interventional
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 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Ability to provide signed and dated informed consent.
- Willingness and ability to comply with all study procedures and protocol requirements for the duration of the study.
- Age 18 to 64 years.
- Chronic, non-penetrating, motor incomplete spinal cord injury [Association Impairment Scale (AIS) grade C or D] occurring ≥12 months prior to enrollment, resulting in impairment in lower limb function.
- Ambulatory with residual gait impairment attributable to spinal cord injury.
- Self-selected gait speed of < 0.8 m/s as measured by the 10 meter walk test.
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- Score of 2 or less on at least 4 measures on the Ambulation subsection of the SCI-Functional Independence scale (SCI-FIS).
- In otherwise good general health as determined by medical history and physical examination.
- Meets all clinical criteria for VNS implantation as determined by the Site PI and clinical care team.
Who cannot join
- Any history of spinal cord injuries by penetrating traumatic, non-traumatic or congenital causes.
- Evidence of right-sided recurrent laryngeal nerve injury on pre-operative laryngoscopy, if required (Note: Participants with a history of right-sided anterior cervical surgery must undergo laryngoscopy prior to surgical scheduling. A finding of right-sided recurrent laryngeal nerve injury results in exclusion).
- Excessive scar tissue on intraoperative assessment that precludes safe implantation (Note: Participants with a history of left-sided anterior cervical surgery will undergo intraoperative assessment of scar tissue. If excessive scar tissue is deemed to preclude safe implantation, the procedure will be abandoned and the participant excluded for safety reasons. A history of left-sided anterior cervical surgery or prior recurrent laryngeal nerve injury alone does not result in exclusion).
- Concomitant clinically significant brain injuries.
- Deficits in language or attention that interfere with study participation.
- Presence of any other implanted electrical stimulation device.
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- Prior injury to the vagus nerve.
- Presence of any other implanted investigational device.
- Neck circumference of > 18.5 inches or significant overlying tissue and/or scarring that may hinder device communication.
- Psychiatric, psychosocial, and/or cognitive disorder or impairment that could interfere with study participation as assessed by medical evaluation.
- Current or past: (a) medical (psychiatric, non-psychiatric) condition, disease, disorder, injury, or disability*; or (b) non-medical situation or circumstance that, in the opinion of the Site PI, study participation:
- may pose a significant or undue risk to the person;
- make it unlikely the person will complete all the study requirements per protocol; or
- may adversely impact the integrity of the data or the validity of the study results.
- [Examples include, but are not limited to, the following types of conditions, diseases or disorders: renal insufficiency or failure, vascular disease, unstable or concerning cardiac disease, endocrinologic concerns (e.g., poorly controlled diabetes), immunosuppression, respiratory issues, psychiatric (e.g., schizophrenia), neurologic (e.g., cognitive, seizure), sickle cell disease, lupus, clotting disorders, active neoplastic disease (excluding basal or squamous cell carcinoma of the skin with intent for curative excision), recent documented history (within the last 3 months) of dysphagia or aspiration difficulty]
- Is female and lactating, pregnant, or plans to become pregnant during the study. Participants of child-bearing potential that are sexually active must use a reliable form of birth control. Acceptable birth control methods: (a) sterilization surgery for women, (b) surgical sterilization implant for women, (c) sterilization surgery for men (including all male partners), (d) Long-acting reversible contraceptives (LARC)-implantable rod and Intrauterine Device (IUD), (e) contraceptive shots/injection every 3 months, (f) oral contraceptives (pills), (g) contraceptive patch, (h) vaginal contraceptive ring, and (i) complete abstinence.
- Abusive use of alcohol or drugs that could interfere with participation, as determined by the Site PI.
- Concurrently participating in another interventional clinical study.
- Requires or plans the use of diathermy, transcranial magnetic stimulation, or electroconvulsive therapy (ECT) during the course of the study.
- Is known to be under incarceration or legal detention as determined by the Site PI.
- Non-English speaking, unless the enrolling site has an IRB-approved translated consent and qualified medical interpreter resources available in the participant's language to support all study visits and procedures.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites
Spaulding Rehabilitation Hospital, Mass General Brigham
Boston, Massachusetts, 02129
Jenny Zhang, 617-952-6354, jzhang71@mgb.org
Chad Swank, PhD
Urgent Surgery Associates, PA
Dallas, Texas, 75204
Madeline Miller, 214-821-1599, mwade@urgentsurgery.com
Michael Foreman, MD
Baylor University Medical Center (BUMC)
Dallas, Texas, 75246
Niroj Ari, 214-820-2821, niroj.ari@bswhealth.org
Rita Hamilton, DO
Texas Biomedical Device Center
Richardson, Texas, 75080
Amy Porter, 972-883-7256, alp160730@utdallas.edu
Alvaro Carrera, 972-883-5397, alvaro.carrera@utdallas.edu
About this study
Official title: Early Feasibility Study of the ReWire System for Closed-Loop Vagus Nerve Stimulation (CLV) Paired With Rehabilitation After Spinal Cord Injury (SCI) - Lower Limb Study
The purpose of this study is to evaluate the safety, feasibility, and preliminary effectiveness of the ReWire system, which delivers vagus nerve stimulation (VNS) paired with lower limb rehabilitation to improve gait in individuals with mobility impairments resulting from chronic, incomplete spinal cord injury (SCI).
Read the detailed description
A randomized, multi-center, double-blinded sham-control early feasibility trial of participants implanted with the ReWire System for spinal cord injury (SCI) with and open label extension.
During the pre-therapy phase, participants will undergo informed consent, baseline assessment, pre-operative evaluation, surgical implantation of the ReWire system, post-surgical assessment, and randomization. Following post-surgical assessment, participants will be block randomized in a 1:1 ratio to either active CLV (Immediate start group) or sham stimulation (Delayed start group) for the double-blind phase.
In double-blind phase, participants will complete up to 18 sessions of lower limb rehabilitation paired with CLV (Immediate start group) or sham stimulation (Delayed start group). Participants will then undergo assessment after completion of all sessions.
In open-label phase, all participants will receive up to an additional 18 sessions of CLV, regardless of their assignment in the double-blind phase. Participants will then undergo assessment after completion of all sessions.
A final, follow-up assessment will be conducted approximately 4 weeks (a month) from the previous assessment and cessation of CLV.
Long-term assessment of safety will be performed twice annually for up to 2 years from the date of implantation, following the completion of final assessment.
- Conditions
- Spinal Cord Injury (SCI), Gait, Reduced Physical Activity, Lower Limb Functions, Walking Impairment, Mobility Impairment
- Being tested
- CLV, Sham
- Keywords
- Vagus nerve stimulation (VNS), Spinal cord injury (SCI), Closed-loop vagus nerve stimulation (CLV), ReWire System, Physical and rehabilitation therapy, XNerve Medical, Texas Biomedical Device Center (TxBDC), Gait, Reduced physical activity, Lower limb functions, Walking impairment, Mobility impairment, Functional mobility
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLVDevice
The participants in this group will be implanted with the ReWire system and receive CLV in the double-blind phase
ShamDevice
The participants in this group will be implanted with the ReWire system and receive Sham in the double-blind phase
| Study group | Role | What they receive |
|---|---|---|
| CLV (Immediate start group) | Experimental | The participants in this arm will be implanted with the device and will receive CLV in double-blind and open-label phases of the study. Receives: Device: CLV |
| Sham (Delayed start group) | Placebo comparator | The participants in this arm will be implanted with the device and will receive sham in double-blind phase and CLV in open-label phase of the study. Receives: Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
ReWire System Safety
Safety of the ReWire system will be assessed by documenting the nature, frequency, severity, and relatedness of adverse events associated with the device, including those attributable to device implantation, stimulation delivery, and rehabilitation procedures.
Measured: From device implantation to up to 2 years following implantation.
ReWire System Feasibility
Feasibility of the ReWire system will be assessed by the proportion of successful stimulation triggering events recorded in the ReWire System log during therapy sessions. The system will be considered feasible if >50% of valid trigger attempts result in successful stimulation delivery.
Measured: All visits after implantation, up to approximately 26 weeks post-enrollment.
Secondary outcomes (12)
6 Meter Walk Test (6MWT)
This measure assesses gait endurance by measuring the distance walked in 6 minutes along a hallway. Determine whether CLV improves six-minute walking test (6MWT) score compared to baseline. This measure is not a scale. Higher distance covered is better.
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
10 Meter Walk Test (10MWT)
This measure assesses walking speed (meter/second) over a short distance. Determine whether CLV improves 10-Meter Walk Test (10-MWT) score compared to baseline. This measure is not a scale. Lower time to complete is better.
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
Timed Up-and Go (TUG)Test
This measure assesses the functional mobility and fall risk by timing participants as they stand from a seated position, walk to a set point, and return to sit. Determine whether CLV improves Timed Up-and Go (TUG)Test score compared to baseline. This measure is not a scale. Lower time to complete is better.
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
Walking Index for Spinal Cord Injury II (WISCI II)
This measure assesses the type and amount of assistance required for walking. Determine whether CLV improves Walking Index for Spinal Cord Injury II (WISCI II) score compared to baseline. This scale is from 0-20. Higher scores indicate better walking performance.
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
Lower Extremity Motor Score (LEMS)
This measure quantifies the strength of five key muscle groups in each lower extremity. Determine whether CLV improves Lower Extremity Motor Score (LEMS) compared to baseline. This scale is from 0 to 50. Higher scores are better.
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
SCI-Functional Independence Scale - Ambulation Subsection (SCI-FIS)
This measure assesses self-perceived limitations with walking and basic mobility. This scale is from 0-24. Higher scores indicate better function.
Measured: At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up).
SCI Independence Measure (SCIM) III
This measure assesses the functional independence (ability to safely perform daily activities without physical or cognitive assistance). This scale is from 0-100. Higher scores indicate greater independence.
Measured: At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up).
International SCI Pain Basic Data Set
This measure is not a scale. It is a questionnaire consisting of items regarding overall pain and items regarding each of the three worst pain problems (assesses pain intensity and classification for each specific pain) in SCI patients.
Measured: At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up).
Observed Functional Change Assessment (OFCA)
This measure is not a scale. It captures participants' reports/observations of positive functional changes (captures emergent functional gains-such as the appearance of new voluntary activation or task initiation-that may not yet be reflected in the numerical thresholds of standardized, performance-based scales).
Measured: At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.
Participant Satisfaction Survey
This measure collects participant-reported feedback regarding usability, tolerability, and overall experience with CLV therapy.
Measured: At week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up).
Participant Blinding Questionnaire
This measure is not a scale. It assesses effectiveness of blinding from the participant perspective.
Measured: At week 14 (double-blind phase).
Therapist Blinding Questionnaire
This measure is not a scale. It assesses effectiveness of blinding from the treating therapist perspective.
Measured: At week 14 (double-blind phase).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start30 Sep 2026 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord Injury (SCI)Studies 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
- Crossover
- Model description
- 1:1 randomization of CLV vs. sham stimulation for 18 sessions post randomization, followed by up to 18 sessions of open label CLV for all participants
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas at Dallas
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Dr. Seth Hays, The University of Texas at Dallas
- Investigators
- Robert Rennaker, PhD, Principal investigator, The University of Texas at DallasJane Wigginton, MD, Principal investigator, The University of Texas at DallasSeth Hays, PhD, Principal investigator, The University of Texas at DallasRita Hamilton, DO, Principal investigator, Baylor University Medical Center (BUMC)Chad Swank, PhD, Principal investigator, Spaulding Rehabilitation Hospital, Mass General BrighamMichael Foreman, MD, Principal investigator, Urgent Surgery Associates, PA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07689227
- Sponsor's protocol ID
- IRB-26-521
- Other IDs
- 5UG3NS131971-02, BSW 026-341
- Status last verified
- Jul 2026
- First submitted
- 17 Jun 2026
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Demographic level data and outcomes.
Publications
Kilgard MP, Epperson JD, Adehunoluwa EA, Swank C, Porter AL, Pruitt DT, Gallaway HL, Stevens C, Gillespie J, Arnold D, Powers MB, Hamilton RG, Naftalis RC, Foreman ML, Wigginton JG, Hays SA, Rennaker RL. Closed-loop vagus nerve stimulation aids recovery from spinal cord injury. Nature. 2025 Jul;643(8073):1030-1036. doi: 10.1038/s41586-025-09028-5. Epub 2025 May 21.
PubMed 40399668