Vagus Nerve Stimulation for Stroke

Overseen By Heidi Schambra

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must not be taking: Anticholinergics, Adrenergic blockers

Disqualifiers: Severe spasticity, Psychiatric disorders, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment Vagus Nerve Stimulation for improving upper limb function after stroke?

Research shows that vagus nerve stimulation (VNS) combined with rehabilitation can improve arm function in stroke patients. Studies found that patients receiving VNS had better motor function improvements compared to those who did not receive VNS, with significant gains in their ability to use their arms. ^{1 2 3 4 5}

Is vagus nerve stimulation (VNS) generally safe for humans?

Vagus nerve stimulation (VNS) has been used for conditions like epilepsy and depression, and while it is generally considered safe, there are some risks. Surgical implantation can lead to infections and other issues like voice changes or breathing difficulties. Non-invasive VNS methods are safer, as they avoid surgery and allow patients to control the stimulation. ^{2 4 6 7 8}

How does vagus nerve stimulation treatment differ from other treatments for stroke?

Vagus nerve stimulation (VNS) is unique because it involves delivering electrical impulses to the vagus nerve, which can enhance motor function recovery when paired with rehabilitation. Unlike traditional stroke treatments, VNS can be both invasive and non-invasive, and it has shown promising results in improving motor impairments and daily living activities in stroke patients. ^{1 2 3 9 10}

What is the purpose of this trial?

In this mechanistic study, 40 individuals with chronic stroke will be implanted with a small vagus nerve stimulation (VNS) device. The study will use a randomized, blinded, crossover design to deliver two conditions in six-week blocks: active VNS or sham VNS, each paired with upper extremity (UE) motor rehabilitation. Assessment visits will occur before and after each block, and will examine neural pathway strength, functional connectivity, and motor and non-motor behaviors. Investigators will test for VNS-induced changes in motor, cognitive, and affective systems, and will identify biomarkers predictive of clinical response.

Research Team

Heidi Schambra, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals who have had a stroke and are now in the chronic phase. They must be suitable candidates for having a small device implanted that stimulates the vagus nerve, which is part of the body's internal control system. Participants will undergo upper extremity rehabilitation as part of the study.

Inclusion Criteria

Ability to provide signed and dated informed consent form

I had a stroke in the upper part of my brain more than a year ago.

My arm's movement ability scores between 20 to 50 on a specific test.

Exclusion Criteria

Deficits in language or attention that interfere with study participation

Presence of any other implanted electrical stimulation device

Prior injury to vagus nerve

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Block 1

Participants receive either active VNS or sham VNS paired with upper extremity motor rehabilitation for 6 weeks

6 weeks

3 sessions per week (in-person)

Treatment Block 2

Participants crossover to receive the alternate condition (active VNS or sham VNS) paired with upper extremity motor rehabilitation for another 6 weeks

6 weeks

3 sessions per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sham VNS Device
• Upper Extremity Rehabilitation
• Vagus Nerve Stimulation (VNS) Device

Trial Overview The study tests if stimulating the vagus nerve with an implanted device can help recovery from stroke when paired with arm rehabilitation exercises. It compares real stimulation (active VNS) to fake stimulation (sham VNS) using a blinded crossover design, meaning participants will experience both conditions without knowing which one they're receiving at any time.

Participant Groups

Group I: Sham VNS first, then Active VNS Experimental Treatment 3 Interventions

Patients will undergo two 6-week intervention blocks, receiving sham VNS first and active VNS second. Blocks consist of three 90-minute sessions per week with a licensed occupational therapist (OT). During these sessions, patients will perform rehabilitation training activities paired with sham VNS during the first block and paired with active VNS during the second block.

Group II: Active VNS first, then Sham VNS Experimental Treatment 3 Interventions

Patients will undergo two 6-week intervention blocks, receiving active VNS first and sham VNS second. Blocks consist of three 90-minute sessions per week with a licensed occupational therapist (OT). During these sessions, patients will perform rehabilitation training activities paired with active VNS during the first block and paired with sham VNS during the second block.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

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]

Vagus nerve stimulation (VNS) combined with rehabilitation was found to be safe and feasible for improving arm function in stroke patients, with all participants completing the therapy despite some serious adverse events related to surgery.

At 90 days post-therapy, patients receiving active VNS showed a significant improvement in upper limb function compared to the control group, with an 88% clinically meaningful response rate, suggesting that VNS may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Kimberley, TJ., Pierce, D., Prudente, CN., et al.[2019]

The VNS-REHAB trial aims to evaluate the safety and efficacy of vagus nerve stimulation (VNS) combined with upper limb rehabilitation in improving motor function in stroke patients, involving up to 120 participants with upper limb weakness due to stroke.

Preliminary studies suggest that VNS paired with rehabilitation leads to clinically meaningful improvements in motor function compared to rehabilitation alone, supporting the need for this larger pivotal trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. Kimberley, TJ., Prudente, CN., Engineer, ND., et al.[2023]

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]

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]

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]

In a pilot trial with 20 stroke survivors, the closed-loop transcutaneous auricular vagus nerve stimulation (MAAVNS) paired with motor rehabilitation showed greater improvement in upper limb function compared to unpaired taVNS, with a higher effect size (Cohen's d = 0.63 vs. 0.30).

Participants receiving MAAVNS required significantly fewer stimulation pulses (36,070) than those receiving unpaired taVNS (45,000), suggesting that the timing and synchronization of stimulation with movement are critical for enhancing rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor Activated Auricular Vagus Nerve Stimulation as a Potential Neuromodulation Approach for Post-Stroke Motor Rehabilitation: A Pilot Study. Badran, BW., Peng, X., Baker-Vogel, B., et al.[2023]

References

1. 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]

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

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation paired with rehabilitation for motor function, mental health and activities of daily living after stroke: a systematic review and meta-analysis. [2023]

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

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. [2023]

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

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

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. Scotland pubmed.ncbi.nlm.nih.gov

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

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

Motor Activated Auricular Vagus Nerve Stimulation as a Potential Neuromodulation Approach for Post-Stroke Motor Rehabilitation: A Pilot Study. [2023]