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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new at-home treatment to help people with Parkinson's disease improve walking and balance. The treatment uses a device that sends mild electrical signals to a nerve in the neck (non-invasive cervical vagal nerve stimulation, or ncVNS) to determine if it can prevent falls and boost independence. Individuals diagnosed with Parkinson's by a VA neurologist, who experience freezing during movement, and can walk unaided for a few minutes might be suitable candidates. The trial compares different ways of using the device, including no treatment, to identify the most effective approach. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could enhance daily living for Parkinson's patients.

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.

What prior data suggests that this non-invasive cervical vagal nerve stimulation is safe for improving gait and balance in Parkinson's disease?

Research has shown that a gentle, non-invasive method to stimulate a nerve in the neck is generally safe for people with Parkinson's disease. Studies have found that this treatment is well-tolerated and helps improve common walking problems in Parkinson's. These studies reported no serious safety issues. Participants in past research used this treatment safely without major side effects, suggesting it could reliably aid movement and balance in people with Parkinson's. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive cervical vagal nerve stimulation (ncVNS) for Parkinson's disease because it offers a unique approach compared to standard treatments like medications and deep brain stimulation. Unlike these traditional options, ncVNS doesn't involve surgery or systemic drugs; instead, it gently stimulates the vagus nerve from outside the body. This method is promising because it could potentially improve symptoms with minimal side effects, allowing individuals to self-administer the treatment at home. Additionally, ncVNS could offer a more convenient and less invasive alternative for managing Parkinson's disease symptoms.

What evidence suggests that non-invasive cervical vagal nerve stimulation is effective for improving gait and balance in Parkinson's disease?

Research has shown that non-invasive cervical vagal nerve stimulation (ncVNS) may benefit people with Parkinson's disease (PD). In this trial, participants will receive ncVNS at varying intensities across different groups. Studies have found that this treatment can significantly improve walking ability, which is crucial because walking difficulties often lead to falls in people with PD. Some research also suggests that ncVNS can reduce stress and inflammation in the body, potentially alleviating other PD symptoms. Although further studies are needed, these findings indicate that ncVNS could be a valuable tool for enhancing safe walking in people with PD. ^{1 3 6 7 8}

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.

Abnormal baseline electrocardiogram within last year

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 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]

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 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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586824005551

Effectiveness of non-invasive vagal nerve stimulation in ... Our finding suggests a potential benefit of nVNS in reducing FOG in PD, but did not demonstrate a significant improvement in other motor symptoms.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39733649/

Effectiveness of non-invasive vagal nerve stimulation in ... Our finding suggests a potential benefit of nVNS in reducing FOG in PD, but did not demonstrate a significant improvement in other motor symptoms.

3. nature.com nature.com/articles/s41531-024-00803-1

Vagus nerve stimulation in Parkinson's disease: a scoping ... These results suggest that RVNS improves motor behavior of PD rats. Collectively, these behavioral assessments provide insight into the ...

4. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1331575/full

Effects of non-invasive vagus nerve stimulation on clinical ... There is mounting evidence that VNS can lower oxidative stress, regulate inflammatory cytokines, and strengthen anti-oxidative mechanisms (Chen et al., 2016).

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S109471592500025X

Noninvasive Vagus Nerve Stimulation in Parkinson's Disease A total of 12 journal articles with data from 287 participants were included. Ten studies reported that VNS significantly improved gait characteristics.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36737716/

Safety and tolerability of adjunct non-invasive vagus nerve ... Safety and tolerability of adjunct non-invasive vagus nerve stimulation in people with parkinson's: a study protocol ... Parkinsons disease; Vagus ...

7. neurologylive.com neurologylive.com/view/noninvasive-vagus-nerve-stimulation-parkinson-shows-safety-efficacy

Noninvasive Vagus Nerve Stimulation for Parkinson ... 1 “Improvements in motor function and gait after 1 month of treatment with nVNS were significant. Our results clearly support additional work to ...

8. neuromodulationjournal.org neuromodulationjournal.org/article/S1094-7159(25)00025-X/abstract

Noninvasive Vagus Nerve Stimulation in Parkinson's Disease Noninvasive VNS demonstrated favorable safety and efficacy for gait impairments in patients with PD, indicating its potential as a versatile intervention ...