Vagus Nerve Stimulation for Stroke

Overseen By Aimee Muir

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor Research Institute

Must not be taking: Anticholinergics, Adrenergic blockers

Disqualifiers: Severe spasticity, Implanted devices, Pregnancy, others

Approved in 1 Jurisdiction 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 aims to assess a new method for helping people regain movement and sensation after a stroke using a wireless nerve stimulation device, known as the Vivistim Paired VNS System. The treatment combines short bursts of electrical stimulation to the vagus nerve with regular rehabilitation exercises. The study will compare two groups: one begins nerve stimulation immediately, while the other starts after a delay. Individuals who experienced a stroke over a year ago and have some movement difficulties (but not severe) might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative recovery methods and contribute to advancing stroke rehabilitation.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications that interfere with VNS, such as drugs that affect neurotransmitter action (e.g., anticholinergics, adrenergic blockers). The protocol does not specify a washout period.

Will I have to stop taking my current medications?

The trial requires that you do not take medications that interfere with vagus nerve stimulation, such as drugs that affect neurotransmitter action (like anticholinergics or adrenergic blockers). If you are on such medications, you may need to stop them to participate.

What prior data suggests that this technique is safe for stroke recovery?

Research has shown that vagus nerve stimulation (VNS) combined with rehabilitation is safe for stroke recovery. One study found that this method not only improves movement but is also well-tolerated by patients. The Vivistim® System, the device used in this therapy, has FDA approval for treating arm and hand issues after a stroke, indicating its safety for this use. Additionally, patients using VNS therapy have experienced long-term benefits, with some maintaining improvements for up to three years. Overall, VNS combined with rehabilitation appears to be a safe and promising option for stroke recovery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about vagus nerve stimulation (VNS) for stroke recovery because it offers a novel approach to rehabilitation. Unlike traditional stroke treatments that primarily focus on physical therapy and medication, VNS combines rehabilitation exercises with electrical stimulation of the vagus nerve, potentially enhancing brain plasticity and recovery. This wireless nerve stimulation device is non-invasive and can be used both in clinical settings and at home, making it more accessible and convenient for patients. By directly engaging the nervous system, VNS may accelerate and improve the recovery process, offering new hope for stroke survivors.

What evidence suggests that this device is effective for stroke recovery?

Research has shown that vagus nerve stimulation (VNS) combined with rehabilitation can significantly enhance movement recovery after a stroke. In this trial, participants will join one of two groups: the Immediate Start Vagus Nerve Stimulation group, receiving active VNS during rehabilitation, or the Delayed Start Vagus Nerve Stimulation group, initially receiving placebo stimulation before transitioning to active VNS. Studies have found that this treatment can improve motor skills, with benefits lasting up to three years. The FDA has approved paired VNS therapy for treating movement issues in the arms of stroke survivors. It activates brain pathways that aid the body in adjusting and regaining function, a process known as neural plasticity. This treatment is safe and effective, providing a drug-free option for stroke recovery. ^{1 2 3 5 6}

Who Is on the Research Team?

Rita Hamilton, DO

Principal Investigator

Baylor Scott & White Institute for Rehabilitation

Jane Wigginton, MD

Principal Investigator

University of Texas Southwestern Medical Center

Michael Foreman, MD, FACS

Principal Investigator

Baylor Health Care System

Ann Marie Warren, PhD

Principal Investigator

Baylor Health Care System

Richard Naftalis, MD, FAANS, FACS

Principal Investigator

Baylor Health Care System

Robert Rennaker, PhD

Principal Investigator

University of Texas at Dallas

Seth Hays, PhD

Principal Investigator

University of Texas at Dallas

Michael Kilgard, PhD

Principal Investigator

University of Texas at Dallas

Mark Powers, PhD

Principal Investigator

Baylor Health Care System

Are You a Good Fit for This Trial?

This trial is for adults aged 22-79 who've had a stroke at least one year ago and have some arm weakness. They must be able to follow the study plan, use birth control if capable of pregnancy, and meet surgical criteria for a nerve stimulation device implant.

Inclusion 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

Women of reproductive potential must use contraceptive protection

Exclusion Criteria

You have severe muscle stiffness.

Medical or mental instability that would likely interfere with study protocol

You currently need or will soon need diathermy treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Rehabilitation with VNS

Participants receive rehabilitation with either active or placebo VNS for 18 in-office sessions over six weeks

6 weeks

18 visits (in-person)

Phase 2: Open-label Extension

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

6 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Wireless Nerve Stimulation Device

Trial Overview The trial tests a new wireless nerve stimulation device during rehab exercises to see if it helps recovery after stroke better than not using the device (placebo). Participants will receive brief pulses of vagus nerve stimulation aimed at improving motor and sensory functions.

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 six weeks during Phase 1. For Phase 2, all subjects will be provided with 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 six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.

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 six weeks during Phase 1. For Phase 2, all subjects will be provided with 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 six weeks. Additionally, participants may be provided with a system of rehabilitative devices to utilize at home.

Wireless Nerve Stimulation Device is already approved in United States for the following indications:

Approved in United States as Vivistim Paired VNS System for:

• Moderate to severe upper extremity motor deficits associated with chronic ischemic stroke

Who Is Running the Clinical Trial?

Baylor Research Institute

Lead Sponsor

Trials

210

Recruited

205,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

The University of Texas at Dallas

Collaborator

Trials

71

Recruited

108,000+

Published Research Related to This Trial

The modified implantation procedure for the VNS Therapy(®) System in 10 healthy Beagle dogs was successful without any intraoperative complications, indicating that the technique is safe and feasible.

Postoperative complications included a high incidence of seroma formation (70%) and issues with the device such as lead twisting (50%) and anchor tether dislodgement (40%), highlighting the need for careful monitoring and potential improvements in surgical technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulator Placement in Dogs: Surgical Implantation Technique, Complications, Long-Term Follow-Up, and Practical Considerations. Martlé, V., Van Ham, LM., Boon, P., et al.[2018]

In a study of 247 patients who received vagus nerve stimulation (VNS) devices over a mean follow-up of 12 years, surgical complications occurred in 8.6% of procedures, with the most common being postoperative hematoma (1.9%) and infection (2.6%).

Hardware complications were less frequent at 3.7%, primarily involving lead fractures or malfunctions (3.0%), indicating that while VNS implantation is generally safe, there are notable risks that can lead to significant patient suffering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications and safety of vagus nerve stimulation: 25 years of experience at a single center. Révész, D., Rydenhag, B., Ben-Menachem, E.[2017]

The Vagus Nerve Stimulation (VNS) Therapy System is the first FDA-approved device for treating drug-resistant epilepsy, showcasing significant technological advancements over two decades, including improvements in hardware and software.

This review provides a comprehensive comparison of various VNS generator models, highlighting differences in battery longevity and stimulation modes, which can help healthcare providers make informed decisions about device selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy. Afra, P., Adamolekun, B., Aydemir, S., et al.[2022]

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]

Vagus nerve stimulation (VNS) is an effective adjunct therapy for patients with epilepsy who do not respond to anti-epileptic drugs, and it is increasingly being explored for other medical conditions.

While VNS can cause benign but frightening side effects that increase with stimulation intensity, serious life-threatening events are rare, highlighting the importance of recognizing and managing these symptoms promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: a pre-hospital case report. Mohrsen, SA.[2022]

Vagus nerve stimulation (VNS), both invasive and non-invasive, significantly improves motor function and reduces motor impairment in stroke patients, based on a systematic review and meta-analysis of multiple studies.

The study found no significant difference in adverse events between VNS and control groups, suggesting that VNS is a safe intervention for enhancing recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of vagus nerve stimulation on upper limb function in patients with stroke: a systematic review and meta-analysis. Abdullahi, A., Wong, TWL., Ng, SSM.[2023]

The subpectoral (SP) implantation technique for vagus nerve stimulators (VNS) offers improved cosmetic outcomes and increased durability against tampering and trauma compared to the traditional subcutaneous (SQ) method, with no cases of excessive generator mobility in the SP group.

Infection rates were comparable between the SP group (2.5%) and the SQ group (2.9%), suggesting that the SP technique is equally safe while providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subpectoral implantation of the vagus nerve stimulator. Bauman, JA., Ridgway, EB., Devinsky, O., et al.[2006]

The ADNS-300 system for vagus nerve stimulation (VNS) was successfully implanted in all three patients, demonstrating its feasibility for therapeutic use and recording of nerve activity.

Two out of three patients experienced a significant reduction in seizure frequency (43% and 40%), indicating that the ADNS-300 system may effectively reduce seizures in refractory epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: pilot trial at Ghent University Hospital. El Tahry, R., Raedt, R., Mollet, L., et al.[2012]

The Vivistim® Paired VNS™ System, approved by the FDA in 2021, is safe and effective for improving motor deficits in chronic ischemic stroke survivors, based on a pivotal trial involving 108 participants.

The study reported a lower rate of surgery-related adverse events compared to previous VNS implantations for epilepsy, with no serious adverse events linked to device stimulation, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial. Liu, CY., Russin, J., Adelson, DP., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04534556

Study Details | NCT04534556 | Wireless Nerve Stimulation ... The purpose of this study is to extend these findings and evaluate whether VNS delivered with the new device paired with rehabilitation represents a safe and ...

2. vivistim.com vivistim.com/clinical-data/

Clinical Data Paired VNS is an FDA-approved, valuable treatment option providing long-term benefits for individuals with chronic upper extremity limitations after stroke.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0003999323001478

Vagus Nerve Stimulation Paired With Upper-Limb ... Paired VNS therapy is a new FDA-approved therapy for chronic stroke survivors. Motor gains after Paired VNS were maintained out to 3 years after therapy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4689175/

Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation ... The main objective of the study was to evaluate the safety and feasibility of paired VNS therapy after stroke and to provide clinical data for sample size ...

5. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf21/P210007B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The Vivistim® System when used as intended, provides a drug-free way to treat upper extremity motor deficits associated with a stroke by pairing rehabilitation ...

6. 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.