Non-Invasive Vagal Nerve Stimulation for Parkinson's Disease

Overseen By Alexandria N Umbarger, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must be taking: Parkinson's medications

Must not be taking: Anticholinergics, Cholinesterase inhibitors

Disqualifiers: Musculoskeletal, Neurological, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

More than 110,000 US Veterans living with Parkinson's disease (PD) currently receive PD-related care and services from the VA. Fall prevention is a priority for Veterans living PD. Gait disturbances are a major cause for functional dependence and the largest risk factor for falls, institutionalization, and death in PD. This SPiRE addresses the need to advance nonpharmacological rehabilitative health care of Veterans and maximizing functional outcomes by developing a non-invasive, neuromodulatory transcutaneous cervical Vagal Nerve Stimulation as an at-home intervention to improve gait and balance. This pilot clinical trial will assist with future efforts and priorities of the VA to prolong independent living and quality of life by minimizing gait and balance dysfunction experienced by Veterans living with PD.

Will I have to stop taking my current medications?

The trial requires that your Parkinson's disease medications remain stable for 4 weeks before and throughout the study, so you should not stop taking them. However, if you are on centrally acting anticholinergics or cholinesterase inhibitors, you cannot participate in the trial.

Is non-invasive vagal nerve stimulation safe for humans?

Non-invasive vagal nerve stimulation (VNS) is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant risk of severe adverse events compared to controls, making it a feasible option for clinical use. ^{1 2 3 4 5}

How is non-invasive cervical vagal nerve stimulation (ncVNS) different from other treatments for Parkinson's disease?

Non-invasive cervical vagal nerve stimulation (ncVNS) is unique because it offers a non-surgical way to stimulate the vagus nerve, potentially improving motor function and reducing inflammation in Parkinson's disease. Unlike traditional treatments, it does not involve medication and avoids the side effects associated with drugs, making it a novel approach for managing symptoms. ^{1 6 7 8 9}

What data supports the effectiveness of the treatment Non-invasive cervical vagal nerve stimulation (ncVNS) for Parkinson's Disease?

Research on vagus nerve stimulation (VNS) in animal models of Parkinson's disease shows that it can improve movement and protect brain cells. Non-invasive forms of VNS, like transcutaneous auricular vagus nerve stimulation (taVNS), have shown preliminary safety and effectiveness in people with Parkinson's disease. ^{1 6 8 10 11}

Who Is on the Research Team?

Sandra L. Kletzel, PhD BA

Principal Investigator

Edward Hines Jr. VA Hospital, Hines, IL

Are You a Good Fit for This Trial?

This trial is for US Veterans with Parkinson's Disease who experience gait disturbances, which can lead to falls and decreased independence. The goal is to help them improve their walking and balance through a non-drug treatment that they can use at home.

Inclusion Criteria

My Parkinson's medication has been stable for 4 weeks and will remain so during the study.

I experience sudden stops when I walk.

I have been diagnosed with Parkinson's disease by a VA neurologist.

Exclusion Criteria

I am unable to make my own health care decisions.

I have not had spine or leg surgery in the last year.

I am taking medication for nerve-related symptoms or memory issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham vagal nerve stimulation at home for 4 weeks

4 weeks

Daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Non-invasive cervical vagal nerve stimulation (ncVNS)

Trial Overview The intervention being tested is a non-invasive cervical vagal nerve stimulation (ncVNS) device. This pilot clinical trial aims to see if using this device at home can help improve gait and balance in veterans with Parkinson's Disease.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

Vagal nerve stimulation at the highest intensity tolerated by the participant. Participants will self-administered at this intensity for 12 minutes each day over 4 weeks.

Group II: Group 1 Experimental Treatment 1 Intervention

Vagal nerve stimulation at an intensity under 10 units. Participants will self-administered at this intensity for 2 minutes each day over 4 weeks.

Group III: Group 3 Active Control 1 Intervention

This group will not receive any stimulation. Participants will receive their treatment as usual.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., 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]

Noninvasive vagus nerve stimulation (nVNS) was found to be safe and well-tolerated in a pilot study involving 59 adults with chronic migraine, with most adverse events being mild and transient.

While nVNS did not show a significant reduction in headache days compared to sham treatment during the randomized phase, participants who continued with nVNS in the open-label phase experienced a meaningful decrease in headache days after 8 months, suggesting potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. Silberstein, SD., Calhoun, AH., Lipton, RB., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Multi-session transcutaneous auricular vagus nerve stimulation for Parkinson's disease: evaluating feasibility, safety, and preliminary efficacy. [2023]

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

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway. [2023]

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

Vagus nerve stimulation improves locomotion and neuronal populations in a model of Parkinson's disease. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats. [2021]

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

Differential effects of vagus nerve stimulation paradigms guide clinical development for Parkinson's disease. [2021]

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

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

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

Adverse events in children receiving intermittent left vagal nerve stimulation. [2019]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on cervical vagus nerve stimulation for the treatment of primary headache disorders: a review. [2022]

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

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]