Vagal Nerve Stimulation for Multiple Sclerosis

(VANISH-MS Trial)

Overseen By Shayna Pehel

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: High efficacy DMT

Must not be taking: Beta-blockers, Calcium channel blockers, SP1 inhibitors

Disqualifiers: Stroke, Parkinson's, Diabetes, others

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

Compensation: Varies

Number of Visits: 20

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if stimulating the vagus nerve, a key nerve in the body, can alleviate inflammation and emotional distress in people with multiple sclerosis (MS). Participants will try one of two types of vagus nerve stimulation (either near the ear or neck) or a standard brain stimulation method, known as Remotely Supervised Transcranial Direct Current Stimulation (RS-tDCS), to compare their effects. The trial seeks women aged 25-65 who have MS, have been stable on their current treatment for at least six months, and can use mobile devices. As an unphased trial, this study offers a unique opportunity to explore innovative treatments that could enhance the quality of life for MS patients.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that can affect heart rate variability, such as beta-blockers, calcium channel blockers, cardiac glycosides, and SP1 inhibitors like Fingolimod, Siponimod, Ozanimod, and Ponesimod.

What prior data suggests that vagal nerve stimulation is safe for multiple sclerosis?

Research has shown that stimulating the vagus nerve in the ear (taVNS) and neck (tcVNS) is generally safe. Studies confirm that taVNS is well-tolerated, with few side effects, as proven in trials comparing it to a placebo. Another study demonstrated its safety for supervised home use.

For tcVNS, research suggests it is also safe, though a standard treatment plan remains undeveloped. Overall, both methods appear promising as non-invasive treatments with minimal side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Multiple Sclerosis (MS) because they offer a new way to potentially manage the condition. Unlike traditional MS therapies that often involve medications targeting the immune system, these treatments focus on vagus nerve stimulation. The transcutaneous auricular and cervical vagus nerve stimulations (taVNS and tcVNS) are non-invasive methods that use electrical impulses to stimulate the vagus nerve, which may help regulate immune response and reduce inflammation. This innovative approach could offer a new avenue for symptom management in MS without the side effects associated with conventional drug therapies.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

This trial will compare different methods of vagus nerve stimulation for managing multiple sclerosis (MS) symptoms. Studies have shown that stimulating the vagus nerve (VNS) might help manage MS symptoms by reducing inflammation and emotional distress. Research suggests that transcutaneous auricular vagus nerve stimulation (taVNS), which participants in this trial may receive, can significantly improve sleep and overall quality of life. Another method under study, transcutaneous cervical vagus nerve stimulation (tcVNS), may also help manage symptoms. Both taVNS and tcVNS aim to stimulate the vagus nerve, which helps control inflammation and mood. These early studies suggest that VNS could be a promising way to reduce symptoms for people with MS. ^{1 2 3 4 6}

Who Is on the Research Team?

Leigh Charvet, PhD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for individuals with multiple sclerosis (MS) who are interested in a non-drug approach to manage their symptoms. Participants should be willing to undergo novel nerve stimulation treatments remotely and have the ability to report on symptom changes.

Inclusion Criteria

I can complete daily tasks with little to no help.

I am between 25 and 65 years old.

SymptoMScreen Score ≥12

Exclusion Criteria

I have had surgery on my vagus nerve.

Nicotine use in the past 6 months (smoking/vaping)

I have been diagnosed with POTS.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either taVNS, tcVNS, or tDCS for symptom management in MS

4 weeks

20 daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Remotely Supervised Transcranial Direct Current Stimulation (RS - tDCS)
• Remotely Supervised Transcutaneous Auricular Vagus Nerve Stimulation (RS - taVNS)
• Remotely Supervised Transcutaneous Cervical Vagus Nerve Stimulation (RS - tcVNS)

Trial Overview The study tests two types of vagal nerve stimulation: one applied at the ear (taVNS) and another at the neck (tcVNS), against a control method using brain stimulation (tDCS). The goal is to see which method is more feasible and effective in reducing MS symptoms.

How Is the Trial Designed?

Group I: Active tcVNS Experimental Treatment 1 Intervention

20 daily 20-minute sessions of active tcVNS.

Group II: Active taVNS Experimental Treatment 1 Intervention

20 daily 60-minute sessions of active taVNS.

Group III: Active DLPFC tDCS Active Control 1 Intervention

20 daily 20-minute sessions of active tDCS.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive and less expensive alternative to invasive vagus nerve stimulation (VNS), which is used to treat conditions like epilepsy and depression, but requires further research to optimize stimulation sites and parameters.

tVNS has the potential to activate various brain areas and may be effective for a wide range of conditions, including medication-refractory epilepsy, depression, migraines, and more, suggesting it could become a standard treatment for enhancing autonomic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. Hilz, MJ.[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]

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]

The study demonstrated that remote supervised administration of transcutaneous auricular vagus nerve stimulation (taVNS) at home is feasible for 12 patients with autism spectrum disorder (ASD), achieving an 88.5% completion rate over 132 sessions.

Initial results indicated improvements in anxiety and sleep measures after 2 weeks of treatment, suggesting potential efficacy that warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy. Black, B., Hunter, S., Cottrell, H., et al.[2023]

Vagus nerve stimulation (VNS) showed promising results in improving postural cerebellar tremor and dysphagia in three patients with multiple sclerosis over a period of two to three months.

The improvements are likely linked to VNS's effect on the nucleus tractus solitarius, which plays a role in controlling swallowing and motor functions, suggesting VNS could be a novel treatment option for severe MS symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagal nerve stimulation improves cerebellar tremor and dysphagia in multiple sclerosis. Marrosu, F., Maleci, A., Cocco, E., et al.[2007]

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 FDA-approved treatment for conditions like drug-refractory epilepsy and treatment-refractory major depressive disorders, working by influencing both the brain and internal organs through its effects on the autonomic and neuroendocrine systems.

VNS operates via the cholinergic anti-inflammatory pathway, which helps regulate immune responses and reduce inflammation, highlighting its potential for treating a variety of neuropsychiatric and systemic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications. Fang, YT., Lin, YT., Tseng, WL., et al.[2023]

Cervical vagus nerve stimulation (VNS) can potentially treat various disorders, and this study developed models to estimate the engagement of different nerve fiber types (A, B, and C fibers) based on physiological responses like EMG, heart rate, and breathing intervals in anesthetized rats.

The findings suggest that specific physiological markers correlate with the activation of different fiber types, which could allow for noninvasive monitoring of VNS therapy in humans, enhancing the precision of treatment calibration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. Chang, YC., Cracchiolo, M., Ahmed, U., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06816004?cond=multiple+sclerosis&aggFilters=status%3A

NCT06816004 | Noninvasive Vagal Nerve Stimulation Growing evidence suggests that vagal nerve stimulation (VNS) may be novel and effective in the management of the symptom burden of multiple sclerosis (MS) ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06816004/noninvasive-vagal-nerve-stimulation

Noninvasive Vagal Nerve Stimulation | Clinical Research ... Growing evidence suggests that vagal nerve stimulation (VNS) may be novel and effective in the management of the symptom burden of multiple ...

3. withpower.com withpower.com/trial/vagal-nerve-stimulation-for-multiple-sclerosis-0a7c5

Vagal Nerve Stimulation for Multiple Sclerosis Growing evidence suggests that vagal nerve stimulation (VNS) may be novel and effective in the management of the symptom burden of multiple sclerosis (MS) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9402278/

A pilot randomized controlled trial of supervised, at-home, self ... This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945725002540

Transcutaneous auricular vagus nerve stimulation (taVNS ... taVNS significantly improved sleep quality, insomnia severity, and overall quality of life compared to sham.

6. tandfonline.com tandfonline.com/doi/full/10.1080/09638288.2024.2313123

Clinical application of transcutaneous auricular vagus ... This study aimed to explore the therapeutic use of taVNS, optimal stimulation parameters, effective sham protocols, and safety.