Vagus Nerve Stimulation for Spinal Cord Injury

Overseen by Rita Hamilton, DO

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Baylor Research Institute

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Brain injuries, Alcohol abuse, Immunodeficiency, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment that sends small electrical pulses to a nerve in the neck during physical therapy to help people with spinal cord injuries regain movement and feeling in their arms. The treatment helps the brain and spinal cord 'rewire' themselves, making recovery more effective.

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 data supports the effectiveness of the treatment Vagus Nerve Stimulation for Spinal Cord Injury?

Research shows that Vagus Nerve Stimulation (VNS) paired with rehabilitation can enhance recovery in neurological disorders by promoting neural plasticity (the brain's ability to change and adapt). Studies in animals and some clinical trials suggest that VNS can improve motor and sensory functions after injuries like spinal cord injury and stroke. ^{1 2 3 4 5}

Is vagus nerve stimulation generally safe for humans?

Vagus nerve stimulation (VNS) has been used safely for conditions like epilepsy and depression, with some risks mainly related to surgical implantation, such as infection and temporary voice changes. Non-invasive VNS methods improve safety by avoiding surgery, and common side effects include hoarseness, cough, and headache, which are usually temporary. ^{6 7 8 9 10}

How is the treatment Vagus Nerve Stimulation for Spinal Cord Injury different from other treatments?

Vagus Nerve Stimulation (VNS) is unique because it uses electrical stimulation of the vagus nerve to enhance the brain's ability to rewire itself, promoting recovery of motor function after spinal cord injury. Unlike other treatments, VNS is paired with rehabilitation exercises to specifically strengthen neural connections, leading to more effective and lasting recovery. ^{2 3 5 11 12}

Research Team

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

Michael Foreman, MD FACS

Principal Investigator

Baylor Health Care System

Mark Powers, PhD

Principal Investigator

Baylor Health Care System

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Targeted Plasticity Therapy (Neuromodulation)

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.

Participant Groups

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.

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+

Dr. Richard Benson

The University of Texas at Dallas

Chief Executive Officer since 2016

PhD in Molecular and Cell Biology from the University of Texas at Dallas

Dr. Patrizia Cavazzoni

The University of Texas at Dallas

Chief Medical Officer

MD from Harvard Medical School

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

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]

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) 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]

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) 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 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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Acute Cardiovascular Responses to Vagus Nerve Stimulation after Experimental Spinal Cord Injury. [2022]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

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

8. England 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. [2012]

9. United States pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for refractory epilepsy: a transatlantic experience. [2019]

11. United States 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. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. [2019]