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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment that sends small electrical pulses to a nerve in the neck during physical therapy for stroke patients. The goal is to help the brain and spinal cord form new connections, improving movement and sensation.

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 data supports the idea that Vagus Nerve Stimulation for Stroke is an effective treatment?

The available research shows that Vagus Nerve Stimulation (VNS) is effective in improving motor function in stroke patients. A systematic review and meta-analysis found that both invasive and non-invasive VNS significantly improved motor impairment and function compared to control groups. This suggests that VNS can be a beneficial treatment for stroke recovery. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Wireless Nerve Stimulation Device, Vivistim Paired VNS System, Vagus Nerve Stimulation Device, Wireless Nerve Stimulation Device for stroke?

Research shows that Vagus Nerve Stimulation (VNS) paired with rehabilitation can improve motor function in stroke patients, as it was approved by the FDA for this purpose in 2021. Additionally, a systematic review found that both invasive and non-invasive VNS significantly improved motor impairment and function in stroke patients compared to control groups. ^{1 2 3 4 5}

What safety data is available for Vagus Nerve Stimulation in stroke treatment?

Vagus Nerve Stimulation (VNS) has been used in over 125,000 patients for epilepsy, showing it is generally well-tolerated and safe. The Vivistim Paired VNS System, approved by the FDA in 2021 for stroke rehabilitation, involves a surgical procedure that is typically safe. Common surgical complications include postoperative hematoma, infection, and vocal cord palsy, each occurring in about 2% of cases. Hardware complications like lead fracture occur in about 3% of cases. Non-invasive VNS systems offer improved safety by avoiding surgery. Overall, VNS is considered relatively safe, but it carries some risks, especially related to surgery and hardware issues. ^{1 3 5 6 7}

Is vagus nerve stimulation generally safe for humans?

Vagus nerve stimulation (VNS) has been used in over 125,000 patients for conditions like epilepsy and is generally well-tolerated and safe. However, it can have some risks, such as infection, voice changes, and rare cases of heart-related issues during surgery. Newer non-invasive VNS systems improve safety by avoiding surgery. ^{1 3 5 6 7}

Is the Wireless Nerve Stimulation Device a promising treatment for stroke?

Yes, the Wireless Nerve Stimulation Device, also known as the Vivistim Paired VNS System, is a promising treatment for stroke. It has been approved by the FDA to help improve movement in people who have had a stroke and have trouble using their arms and hands. This device has been safely used in many patients for other conditions, showing it can be a reliable option. ^{1 2 5 8 9}

How is the Vivistim Paired VNS System treatment different from other stroke treatments?

The Vivistim Paired VNS System is unique because it combines vagus nerve stimulation (a technique that uses electrical impulses to stimulate the vagus nerve) with rehabilitation exercises to improve motor function in stroke survivors, which is different from traditional stroke treatments that typically focus on medication or physical therapy alone. ^{1 2 5 8 9}

Research Team

Rita Hamilton, DO

Principal Investigator

Baylor Scott & White Institute for Rehabilitation

Michael Foreman, MD, FACS

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

Jane Wigginton, MD

Principal Investigator

University of Texas Southwestern Medical Center

Michael Kilgard, PhD

Principal Investigator

University of Texas at Dallas

Mark Powers, PhD

Principal Investigator

Baylor Health Care System

Ann Marie Warren, PhD

Principal Investigator

Baylor Health Care System

Eligibility Criteria

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

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

Treatment Details

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.

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 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+

Findings from Research

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]

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 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]

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 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]

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 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]

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]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial. [2022]

2. Netherlands 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. [2012]

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

Vagus Nerve Stimulator Placement in Dogs: Surgical Implantation Technique, Complications, Long-Term Follow-Up, and Practical Considerations. [2018]

4. England 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. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy. [2022]

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

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

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

Complications and safety of vagus nerve stimulation: 25 years of experience at a single center. [2017]

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

Subpectoral implantation of the vagus nerve stimulator. [2006]

9. England pubmed.ncbi.nlm.nih.gov

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