Vagus Nerve Stimulation for Spinal Cord Injury

Overseen By Alvaro Carrera

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor Research Institute

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Brain injuries, Alcohol abuse, Immunodeficiency, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 36

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to improve arm and hand movement in people with spinal cord injuries. The treatment uses a device that sends tiny electric pulses to the vagus nerve, helping the brain and spinal cord form new connections during rehabilitation exercises. This approach is known as Targeted Plasticity Therapy, also called Vagus Nerve Stimulation or Targeted Neuroplasticity Therapy. Participants are divided into two groups: one begins the nerve-stimulating treatment immediately, while the other starts with a placebo before switching to the actual treatment. Individuals with a spinal cord injury from trauma over a year ago who still have some arm and hand movement may be eligible to join. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could significantly enhance rehabilitation outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are receiving any therapy that would interfere with vagus nerve stimulation.

What prior data suggests that this technique is safe for spinal cord injury patients?

Research has shown that vagus nerve stimulation (VNS) is generally safe for people. In one study involving individuals with chronic strokes, VNS increased brain connections during rehabilitation exercises and was found to be safe. Another study found that participants receiving VNS alongside therapy experienced better motor recovery without serious side effects. Long-term research indicates that people using VNS experienced lasting improvements in their abilities and quality of life, with no major safety issues reported over a year. These findings suggest that VNS is well-tolerated and may aid recovery in people with spinal cord injuries. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Vagus Nerve Stimulation (VNS) for spinal cord injury because it offers a novel approach compared to traditional rehabilitation methods. Most treatments focus on physical therapy to enhance recovery, but VNS targets the nervous system directly, potentially enhancing the brain's ability to rewire itself after injury. This technique involves stimulating the vagus nerve, which plays a key role in regulating brain plasticity, or the brain's ability to adapt and change. By combining VNS with rehabilitation, there's hope for faster and more effective recovery, giving patients a chance to regain more function and improve their quality of life.

What evidence suggests that this technique is effective for spinal cord injury?

Research has shown that stimulating the vagus nerve (VNS) can aid recovery after brain or nerve injuries. This trial will divide participants into two groups to examine VNS effects on spinal cord injury recovery. The Immediate Start Vagus Nerve Stimulation group will receive active VNS with rehabilitation, while the Delayed Start Vagus Nerve Stimulation group will initially receive placebo stimulation with rehabilitation. Studies have found that VNS, when combined with regular rehabilitation, can enhance movement abilities in stroke patients. Specifically, one study found that combining VNS with rehab led to three times more connections in the brain. Another study demonstrated that individuals with spinal cord injuries experienced better movement recovery following VNS treatment. Additionally, long-term results suggest that these improvements in movement and quality of life can persist for at least a year. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael Foreman, MD FACS

Principal Investigator

Baylor Health Care System

Mark Powers, PhD

Principal Investigator

Baylor Health Care System

Richard Naftalis, MD, FAANS, FACS

Principal Investigator

Baylor Health Care System

Michael Kilgard, PhD

Principal Investigator

University of Texas at Dallas

Robert Rennaker, PhD

Principal Investigator

University of Texas at Dallas

Seth Hays, PhD

Principal Investigator

University of Texas at Dallas

Jane Wigginton, MD

Principal Investigator

University of Texas Southwestern Medical Center

Rita Hamilton, DO

Principal Investigator

Baylor Scott & White Institute for Rehabilitation

Are You a Good Fit for This Trial?

Adults aged 18-64 with a spinal cord injury from trauma at least one year ago, who have some upper limb movement and are in good health. Candidates must be able to follow the study protocol and agree to VNS implantation surgery. Excluded are those with conditions affecting rehabilitation, cognitive deficits preventing informed consent, recent syncope or dysphagia, non-English speakers, pregnant or lactating individuals, substance abusers, participants in other trials, and those with significant medical issues.

Inclusion Criteria

Provision of signed and dated informed consent form

I am a suitable candidate for a vagus nerve stimulator implant.

I am eligible for a VNS implant surgery as confirmed by my medical team.

Exclusion Criteria

You have a history of misusing alcohol or using illegal drugs.

I have health issues that make surgery risky or not possible.

I do not have excessive scar tissue that makes surgery unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive rehabilitation with either active or placebo vagus nerve stimulation for 18 in-office sessions over approximately 6 weeks

6 weeks

18 visits (in-person)

Open-label Extension

Participants have the option to continue with an additional 18 sessions of in-office rehabilitation with active VNS over approximately 6 weeks

6 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments approximately 1 week after the conclusion of therapy

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Targeted Plasticity Therapy

Trial Overview The trial is testing vagus nerve stimulation (VNS) delivered by a new device during rehabilitation exercises for improving motor function in people with spinal cord injuries. It's a double-blind study where half of the participants will receive active VNS and the other half a placebo while undergoing training sessions.

How Is the Trial Designed?

Group I: Immediate Start Vagus Nerve Stimulation group Experimental Treatment 1 Intervention

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.

Group II: Delayed Start Vagus Nerve Stimulation group Placebo Group 1 Intervention

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.

Targeted Plasticity Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Vagus Nerve Stimulation (VNS) for:

• Epilepsy
• Depression
• Stroke rehabilitation
• Spinal cord injury rehabilitation

Approved in European Union as Vagus Nerve Stimulation (VNS) for:

• Epilepsy
• Depression
• Stroke rehabilitation

Who Is Running the Clinical Trial?

Baylor Research Institute

Lead Sponsor

Trials

210

Recruited

205,000+

Wings for Life

Collaborator

Trials

8

Recruited

860+

Defense Advanced Research Projects Agency

Collaborator

Trials

19

Recruited

78,900+

The University of Texas at Dallas

Collaborator

Trials

71

Recruited

108,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a study involving rats with bilateral incomplete spinal cord injuries at C7/8, closed-loop vagus nerve stimulation (VNS) combined with rehabilitative training significantly improved forelimb strength recovery compared to training alone.

The positive effects of VNS on recovery were observed not only in trained tasks but also generalized to untrained forelimb tasks, suggesting that VNS can enhance rehabilitation outcomes even when alpha motor neurons are damaged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools. Darrow, MJ., Torres, M., Sosa, MJ., et al.[2021]

Vagus nerve stimulation (VNS) combined with tactile rehabilitation significantly enhances recovery of somatosensation in a rat model of peripheral nerve injury, with the most effective regimen being 200 VNS pairings per day, four days a week for four weeks.

This study establishes a framework for optimizing VNS therapy dosages, suggesting that a higher frequency and intensity of stimulation sessions leads to better sensory function recovery, which could inform future treatments for chronic sensory loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Delivery of Vagus Nerve Stimulation Requires Many Stimulations Per Session and Many Sessions Per Week Over Many Weeks to Improve Recovery of Somatosensation. Ruiz, AD., Malley, KM., Danaphongse, TT., et al.[2023]

Vagus nerve stimulation (VNS) therapy can effectively control seizures in conditions like epilepsy and may also improve mood and cognitive functions, with a surgical success rate of 50-60% for seizure control.

While VNS therapy has potential benefits, it carries risks of both early and late complications, including infections, vocal cord paralysis, and laryngopharyngeal dysfunction, which occurs in about 66% of patients but is usually temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity. Giordano, F., Zicca, A., Barba, C., et al.[2022]

In a study of pediatric patients with drug-resistant epilepsy, Vagus Nerve Stimulation (VNS) therapy significantly reduced hospitalizations and emergency room visits, indicating improved clinical outcomes after treatment.

VNS therapy also resulted in lower average healthcare costs and a gain in quality-adjusted life years (QALY), with younger patients (1-11 years) gaining an average of 5.96 QALYs and older patients (12-17 years) gaining 4.82 QALYs, demonstrating both economic and health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes, quality of life, and costs associated with implantation of vagus nerve stimulation therapy in pediatric patients with drug-resistant epilepsy. Helmers, SL., Duh, MS., Guérin, A., et al.[2012]

Closed-loop vagus nerve stimulation (CLV) significantly enhances recovery of forelimb function in rats after chronic spinal cord injury (SCI), outperforming rehabilitation alone.

CLV works by strengthening synaptic connections in the brain that control movement, and its benefits continue even after stimulation ends, indicating lasting improvements in neural circuit connectivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. Ganzer, PD., Darrow, MJ., Meyers, EC., et al.[2019]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

In a study of 118 patients with refractory epilepsy who underwent vagus nerve stimulation (VNS), there was a significant average reduction in monthly seizure frequency of 55% over a mean follow-up of 33 months, indicating VNS is an effective long-term treatment option.

VNS was found to be safe, with only 15 patients reporting mild stimulation-related side effects, such as hoarseness or gagging, suggesting that it has a favorable safety profile in a large patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. Vonck, K., Thadani, V., Gilbert, K., et al.[2019]

Intermittent vagus nerve stimulation (VNS) was found to be safe in a rat model of chronic spinal cord injury (SCI), showing only temporary effects on heart rate without causing prolonged hypotension or exacerbating autonomic dysreflexia.

The study suggests that VNS could enhance recovery and promote plasticity in neurological disorders, warranting further research into its therapeutic potential following SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Cardiovascular Responses to Vagus Nerve Stimulation after Experimental Spinal Cord Injury. Sachdeva, R., Krassioukov, AV., Bucksot, JE., et al.[2022]

A 71-year-old man with severe sensory impairment after a stroke showed significant improvements in sensory function following vagus nerve stimulation (VNS) paired with tactile therapy, with no reported side effects during treatment.

After 20 sessions of VNS combined with tactile training, the patient demonstrated lasting enhancements in tactile sensitivity, proprioception, and the ability to identify objects, indicating that this method could be a promising approach for sensory rehabilitation post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient. Kilgard, MP., Rennaker, RL., Alexander, J., et al.[2018]

Cervical vagus nerve stimulation (VNS) can potentially treat various disorders, and this study developed models to estimate the engagement of different nerve fiber types (A, B, and C fibers) based on physiological responses like EMG, heart rate, and breathing intervals in anesthetized rats.

The findings suggest that specific physiological markers correlate with the activation of different fiber types, which could allow for noninvasive monitoring of VNS therapy in humans, enhancing the precision of treatment calibration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. Chang, YC., Cracchiolo, M., Ahmed, U., et al.[2021]

Vagus nerve stimulation (VNS) can enhance neural plasticity when paired with rehabilitative therapies, potentially improving recovery from various neurological disorders such as stroke and traumatic brain injury.

Initial pilot clinical trials suggest that VNS-based therapies may be effective for patients with neurological diseases, indicating a promising avenue for enhancing rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. Hays, SA.[2022]

In a retrospective study of 62 patients treated with vagus nerve stimulation (VNS) for epilepsy, only 6 patients experienced significant seizure reduction, indicating that while VNS can be beneficial, it may not be effective for the majority of patients.

Contrary to its reputation for low adverse effects, the study found that only 9 patients had no adverse effects, with some experiencing severe and even life-threatening complications, highlighting the need for careful monitoring throughout the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vagus nerve stimulation therapy in epilepsy patients: long-term outcome and adverse effects: a retrospective analysis]. Carius, A., Wintermantel, A.[2022]

Citations

1. frontiersin.org frontiersin.org/journals/control-engineering/articles/10.3389/fcteg.2024.1452442/full

State dependent vagus nerve stimulation for targeted ... Vagus nerve stimulation paired with rehabilitative training enhances motor recovery after bilateral spinal cord injury to cervical forelimb motor pools.

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.050479

Long-Term Outcomes of Vagus Nerve Stimulation Paired ... People treated with paired vagus nerve stimulation maintained improvements in UE impairment, activity, participation, and quality-of-life measures at 1 year.

3. nature.com nature.com/articles/s41586-025-09028-5

Closed-loop vagus nerve stimulation aids recovery from ... After 12 weeks of therapy composed of a miniaturized implant selectively activating the vagus nerve on successful movements, 19 people exhibited ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11604078/

Safety and feasibility of paired vagus nerve stimulation with ... Pairing vagus nerve stimulation with traditional rehabilitation therapies results in improved motor recovery in people with stroke.

5. bioelecmed.biomedcentral.com bioelecmed.biomedcentral.com/articles/10.1186/s42234-025-00178-5

Enhancing Neuroplasticity via vagus nerve stimulation to ... Enhancing Neuroplasticity via vagus nerve stimulation to improve urinary dysfunction after spinal cord injury: a perspective. Mia J. Sargusingh, ...