Closed-Loop Vagus Nerve Stimulation (CLV) for Recovery of Gait After Spinal Cord Injury (SCI)

NCT07689227 | Not Yet Recruiting DMC FDA Device

• 3 other identifiers: IRB-26-5215UG3NS131971-02BSW 026-341
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief 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).

Conditions

Spinal Cord Injury (SCI); Gait; Reduced Physical Activity; Lower Limb Functions; Walking Impairment; Mobility Impairment; Functional Mobility

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• 6 Meter Walk Test (6MWT)

  At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.

• 10 Meter Walk Test (10MWT)

  At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.

• Timed Up-and Go (TUG)Test

  At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.

• Walking Index for Spinal Cord Injury II (WISCI II)

  At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.

• Lower Extremity Motor Score (LEMS)

  At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment.

Study Arms (2)

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.

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.

Device: Sham

Interventions

CLV DEVICE

The participants in this group will be implanted with the ReWire system and receive CLV in the double-blind phase

CLV (Immediate start group)

Sham DEVICE

The participants in this group will be implanted with the ReWire system and receive Sham in the double-blind phase

Sham (Delayed start group)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Any history of spinal cord injuries by penetrating traumatic, non-traumatic or congenital causes.
• Concomitant clinically significant brain injuries.
• Deficits in language or attention that interfere with study participation.
• Presence of any other implanted electrical stimulation device.
• 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.

Sponsors & Collaborators

• The University of Texas at Dallas: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (4)

Spaulding Rehabilitation Hospital, Mass General Brigham

Boston, Massachusetts, 02129, United States

Location

Urgent Surgery Associates, PA

Dallas, Texas, 75204, United States

Location

Baylor University Medical Center (BUMC)

Dallas, Texas, 75246, United States

Location

Texas Biomedical Device Center

Richardson, Texas, 75080, United States

Location

Related Publications (1)

• 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.

  PMID: 40399668 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Robert Rennaker, PhD

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

• Jane Wigginton, MD

  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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Porter

CONTACT

972-883-7256; alp160730@utdallas.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: July 8, 2026
• Study Start: September 30, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Upon publication of main study findings.

Locations

US (4)