Closed-Loop Vagus Nerve Stimulation (CLV) for Recovery of Gait

Early Feasibility Study of the ReWire System for Closed-Loop Vagus Nerve Stimulation (CLV) Paired With Rehabilitation After Spinal Cord Injury (SCI)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Gait; Spinal Cord Injury (SCI); Mobility Impairment; Walking Impairment; Functional Mobility; Reduced Physical Activity; Lower Limb Functions
• Intervention / Treatment: Device: CLV; Device: Sham

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amy Porter; Phone Number: 972-883-7256; Email: alp160730@utdallas.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Spaulding Rehabilitation Hospital, Mass General Brigham
      • Principal Investigator: Chad Swank, PhD
      • Contact: Jenny Zhang; Phone Number: 617-952-6354; Email: jzhang71@mgb.org
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center (BUMC)
      • Contact: Niroj Ari; Phone Number: 214-820-2821; Email: niroj.ari@bswhealth.org
      • Principal Investigator: Rita Hamilton, DO
    • Dallas, Texas, United States, 75204
      • Urgent Surgery Associates, PA
      • Principal Investigator: Michael Foreman, MD
      • Contact: Madeline Miller; Phone Number: 214-821-1599; Email: mwade@urgentsurgery.com
    • Richardson, Texas, United States, 75080
      • Texas Biomedical Device Center
      • Contact: Amy Porter; Phone Number: 972-883-7256; Email: alp160730@utdallas.edu
      • Principal Investigator: Robert Rennaker, PhD
      • Principal Investigator: Jane Wigginton, MD
      • Contact: Alvaro Carrera; Phone Number: 972-883-5397; Email: alvaro.carrera@utdallas.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to provide signed and dated informed consent.
2. Willingness and ability to comply with all study procedures and protocol requirements for the duration of the study.
3. Age 18 to 64 years.
4. 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.
5. Ambulatory with residual gait impairment attributable to spinal cord injury.
6. Self-selected gait speed of < 0.8 m/s as measured by the 10 meter walk test.
7. Score of 2 or less on at least 4 measures on the Ambulation subsection of the SCI-Functional Independence scale (SCI-FIS).
8. In otherwise good general health as determined by medical history and physical examination.
9. Meets all clinical criteria for VNS implantation as determined by the Site PI and clinical care team.

Exclusion Criteria:

1. Any history of spinal cord injuries by penetrating traumatic, non-traumatic or congenital causes.
2. 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).
3. 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).
4. Concomitant clinically significant brain injuries.
5. Deficits in language or attention that interfere with study participation.
6. Presence of any other implanted electrical stimulation device.
7. Prior injury to the vagus nerve.
8. Presence of any other implanted investigational device.
9. Neck circumference of > 18.5 inches or significant overlying tissue and/or scarring that may hinder device communication.
10. Psychiatric, psychosocial, and/or cognitive disorder or impairment that could interfere with study participation as assessed by medical evaluation.

11. 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:

    1. may pose a significant or undue risk to the person;
    2. make it unlikely the person will complete all the study requirements per protocol; or
    3. 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]

12. 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.
13. Abusive use of alcohol or drugs that could interfere with participation, as determined by the Site PI.
14. Concurrently participating in another interventional clinical study.
15. Requires or plans the use of diathermy, transcranial magnetic stimulation, or electroconvulsive therapy (ECT) during the course of the study.
16. Is known to be under incarceration or legal detention as determined by the Site PI.
17. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLV (Immediate start group); 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.	Device: CLV; The participants in this group will be implanted with the ReWire system and receive CLV in the double-blind phase
Placebo Comparator: Sham (Delayed start group); 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.	Device: Sham; The participants in this group will be implanted with the ReWire system and receive Sham in the double-blind phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	All visits after implantation, up to approximately 26 weeks post-enrollment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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).	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.	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.	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.	At week 14 (double-blind phase).

Collaborators and Investigators

• Sponsor: The University of Texas at Dallas
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Jane Wigginton, MD, The University of Texas at Dallas; Principal Investigator: Robert Rennaker, PhD, The University of Texas at Dallas; Principal Investigator: Seth Hays, PhD, The University of Texas at Dallas; Principal Investigator: Rita Hamilton, DO, Baylor University Medical Center (BUMC); Principal Investigator: Chad Swank, PhD, Spaulding Rehabilitation Hospital, Mass General Brigham; Principal Investigator: Michael Foreman, MD, Urgent Surgery Associates, PA

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

• Last Update Posted (Actual): July 8, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gait; Functional mobility; Walking impairment; Spinal cord injury (SCI); Mobility impairment; Vagus nerve stimulation (VNS); Closed-loop vagus nerve stimulation (CLV); ReWire System; Physical and rehabilitation therapy; XNerve Medical; Texas Biomedical Device Center (TxBDC); Reduced physical activity; Lower limb functions
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: IRB-xx-xxx; 5UG3NS131971-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Demographic level data and outcomes.
• IPD Sharing Time Frame: Upon publication of main study findings.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes