Targeted Plasticity Therapy for Upper Limb Rehabilitation in Spinal Cord Injuries

March 3, 2026 updated by: Baylor Research Institute
Texas Biomedical Device Center at UT Dallas has developed an innovative strategy to enhance recovery of motor and sensory function after neurological injury termed targeted plasticity therapy (TPT). This technique uses brief pulses of vagus nerve stimulation to engage pro-plasticity neuromodulatory circuits during rehabilitation exercises. Recovery is associated with neural plasticity in spared motor networks in the brain and spinal cord. Moreover, an early feasibility study and an independent, double-blind, placebo-controlled study in chronic stroke participants indicate that VNS is safe in participants with upper limb deficits, and yields a clinically-significant three-fold increase in neural connections during rehabilitation exercises. Given the track record of safety and potential for VNS to enhance recovery of upper limb motor function in spinal cord injured individuals, the purpose of this double blind randomized placebo controlled optional open-label extension study is to assess the safety of using a new device to deliver vagus nerve stimulation to reduce symptom severity in participants with SCI. Additionally, the study will assess the prospective benefit of the system and garner an initial estimate of efficacy for a subsequent trial. Participants may undergo additional sessions of training with VNS.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 64 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Adult, aged 18-64
  • In good general health as evidenced by medical history and diagnosed with first time cervical spinal cord injury resulting in an ASIA grade B, C, or D, and level 1 or better motor function as described by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).
  • SCI caused by trauma that occurred ≥ 12 months prior to enrollment
  • Meets all clinical criteria for the surgical VNS implantation as determined by the PI, surgeon, and anesthesiologist
  • Must demonstrate some residual upper limb and hand movement in either arm
  • Appropriate candidate for VNS implantation
  • Willing and able to comply with the study protocol

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

  • Spinal cord injuries by sharp objects, firearms, and non-traumatic or congenital causes, even if at different levels of the spinal cord
  • Any evidence of recurrent laryngeal nerve injury (Evident during required laryngoscopy for all participants with Prior right-sided anterior cervical surgery- done prior to randomization)
  • Excessive scar tissue marking implantation unsafe (evident at surgery)
  • Concomitant clinically significant brain injuries
  • Prior injury to vagus nerve
  • Prior or current treatment with vagus nerve stimulation
  • Participant receiving any therapy (medication or otherwise) that would interfere with VNS
  • Pregnancy or lactation
  • Clinical complications that hinder or contraindicate the surgical procedure
  • Psychiatric disorders, psychosocial, and/or cognitive impairment that would interfere with study participation, as assessed by medical evaluation
  • Abusive use of alcohol and/or illegal substances use
  • Participation in other interventional clinical trial
  • Participants with known immunodeficiency including participants who are receiving or have received chronic corticosteroids, immunosuppressants, immunostimulating agents or radiation therapy within 6 months
  • Significant comorbidities or conditions associated with high risk for surgical or anesthetic survival (e.g. renal failure, peripheral vascular disease, unstable cardiac disease, poorly controlled diabetes, immunosuppression, etc.).
  • Active neoplastic disease.
  • Participants with significant local circulatory problems, (e.g. thrombophlebitis and lymphedema).
  • Participants with any medical condition or other circumstances that might interfere with their ability to return for follow-up visits in the judgment of the Investigator, including systemic illness, neuromuscular, neurosensory, or musculoskeletal deficiency that would render the participant unable to perform appropriate postoperative rehabilitation.
  • Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of device's safety and performance.
  • Aphasia and other cognitive deficits that make understanding the potential risks and benefits of the study impossible for participant. Inability to personally provide informed consent.
  • A recent history of syncope
  • A recent history of dysphagia
  • Currently require, or are likely to require diathermy
  • Significant respiratory issues that would interfere with participation
  • Non-English speaking
  • Patients who are acutely suicidal and/or have been admitted for a suicide attempt
  • Incarceration or legal detention

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Device Feasibility
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immediate Start Vagus Nerve Stimulation group
The Immediate Start VNS group will receive rehabilitation and active stimulation for 18 in-office sessions over the course of approximately 6 weeks during phase 1. For phase 2, all subjects will be provided the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.
Device: Active Vagus Nerve Stimulation
Stimulation of the vagus nerve that is paired with upper extremity rehabilitation. VNS stimulation as described in the current study consists of 0.5 s trains of 0.8 mA 100 µs biphasic pulses delivered at 30 Hz. Stimulation trains are delivered only during rehabilitation.
Other Names:
  • VNS
  • vagus nerve stimulation
  • paired VNS
Placebo Comparator: Delayed Start Vagus Nerve Stimulation group
The Delayed Start VNS group will receive equivalent rehabilitation with placebo stimulation for 18 in-office sessions over the course of approximately 6 weeks during phase 1. For phase 2, all subjects will be provided the option to participate in an open-label extension consisting of an additional 18 sessions of in-office rehabilitation with active VNS over the course of approximately 6 weeks. Participants that elect to continue in the open-label extension will be assessed approximately 1 week after the conclusion of the additional 18 sessions of therapy.
Device: Placebo Vagus Nerve Stimulation
During Phase 1 of the study, the placebo group will receive a minimal amount of stimulation that fails to sufficiently activate the nerve, unknown to the participant and therapists. All participants will receive active stimulation during the Phase 2 open-label portion of the study.
Other Names:
  • placebo
  • control
Experimental: Follow-On Study Group
The Follow-On Study group will receive up to 112 rehabilitative sessions with active VNS over the course of approximately 36 weeks after completion of Phase II. Participants will be provided with a system of rehabilitative devices to utilize at home.
Device: Active Vagus Nerve Stimulation
Stimulation of the vagus nerve that is paired with upper extremity rehabilitation. VNS stimulation as described in the current study consists of 0.5 s trains of 0.8 mA 100 µs biphasic pulses delivered at 30 Hz. Stimulation trains are delivered only during rehabilitation.
Other Names:
  • VNS
  • vagus nerve stimulation
  • paired VNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events [Device Safety]
Time Frame: Week 1, 4, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20
Review of adverse events reported throughout the trial will be used to inform the potential risks associated with the ReStore system and provide a better understanding of risk/benefit analysis.
Week 1, 4, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative Force and Range of Motion Assessment
Time Frame: Week 1, 6, 13, 20
This is a physical assessment of upper limb changes in force/torque as a result of VNS paired rehabilitation. The primary endpoints will be: 10% increase in finger pinch and flexion force following active VNS, 10% increase in wrist flexion and extension force following active VNS, and 10% increase in wrist pronation and supination force following active VNS. This will serve as an efficacy measurement to use as basis for estimate of sample size for a pivotal trial.
Week 1, 6, 13, 20
Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP)
Time Frame: Week 1, 6, 13, 20
Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) is a measure used for spinal cord injury patients. The measure includes five subsets of questions designed to quantitatively measure clinical upper limb impairment (Kalsi-Ryan et al., 2012). The primary endpoint will be: >4 point shift in GRASSP assessment following active VNS. This will serve as an efficacy measurement to use as basis for estimate of sample size for a pivotal trial.
Week 1, 6, 13, 20
Restore System Feasibility during Rehabilitation
Time Frame: Weeks 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19
If stimulation delivery is successful during the active portion of therapy sessions then the system is feasible to use. The primary endpoint will be: greater than 50% of the valid attempts to stimulate are successful per the ReStore system log.
Weeks 7, 8, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19
Jebsen-Taylor Hand Function Test
Time Frame: Week 1, 6, 13, 20
Seven-item test of hand functions commonly used in activities of daily living (Jebsen et al, 1969). The items tested include range of fine motor, weighted and non-weighted hand function activities. The primary endpoint will be: 10% improvement in time to complete JTHF test following VNS therapy
Week 1, 6, 13, 20

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor Research Institute

Collaborators

University of Texas Southwestern Medical Center
Wings for Life
The University of Texas at Dallas
Defense Advanced Research Projects Agency

Investigators

  • Principal Investigator: Jane Wigginton, MD, University of Texas Southwestern Medical Center
  • Study Director: Mark Powers, PhD, Baylor Health Care System
  • Study Director: Richard Naftalis, MD, FAANS, FACS, Baylor Health Care System
  • Principal Investigator: Rita Hamilton, DO, Baylor Scott & White Institute for Rehabilitation
  • Study Director: Michael Foreman, MD FACS, Baylor Health Care System
  • Principal Investigator: Robert Rennaker, PhD, The University of Texas at Dallas
  • Principal Investigator: Michael Kilgard, PhD, The University of Texas at Dallas
  • Study Director: Seth Hays, PhD, The University of Texas at Dallas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2021

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

November 13, 2019

First Submitted That Met QC Criteria

February 26, 2020

First Posted (Actual)

February 28, 2020

Study Record Updates

Last Update Posted (Actual)

March 4, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 019-356
  • N66001-17-2-4011 (Other Grant/Funding Number: Naval Information Warfare Center, Pacific)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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