Vagus Nerve Stimulation for Multiple Sclerosis

Overseen By Pamela David Gerecht

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Clemastine, Bexarotene, others

Disqualifiers: Seizures, Brain trauma, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 4 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if stimulating the vagus nerve in combination with a motor task in people with multiple sclerosis can improve motor function. The main questions it aims to answer are: * Is stimulating the vagus nerve safe and feasible after demyelinating episodes? * Does a paired motor task with vagus nerve stimulation improve motor function with someone who has multiple sclerosis? Researchers will compare active vagus nerve stimulation to a sham stimulation to see if the paired vagus nerve stimulation can improve motor control. Participants will: * Come in for study visits over a six month period. Study visits are three times weekly for the first month, then single follow up visits at two, three, and six months. * During study visits, participants will complete 30 minutes of the paired vagus nerve stimulation with a motor task, specifically the grooved peg test. * At various timepoints in the study, motor and disability tests will be administered to see if there are any changes in motor control for that participants. These tests include the timed 25 foot walk test, expanded disability scale, the upper extremity portion of the Fugl-Meyer Assessment, and the Multiple Sclerosis Impact Scale - 29.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you are allowed to continue or start disease-modifying therapy to help manage multiple sclerosis during the study.

What data supports the effectiveness of the treatment Closed Loop Trans-Auricular Vagus Nerve Stimulation System for Multiple Sclerosis?

Vagus nerve stimulation (VNS) has been shown to be effective in treating epilepsy and depression, and it is being explored for various inflammatory and systemic diseases due to its ability to modulate the immune system and reduce inflammation. This suggests potential benefits for conditions like Multiple Sclerosis, which involves immune system dysfunction. ^{1 2 3 4 5}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation (VNS) is generally considered safe, with most side effects being mild and temporary, such as voice changes, tingling, or ear pain. Serious issues are rare, especially with non-invasive methods, which avoid surgery and allow patients to control the stimulation themselves. ^{1 6 7 8 9}

How does the Closed Loop Trans-Auricular Vagus Nerve Stimulation System treatment for Multiple Sclerosis differ from other treatments?

This treatment is unique because it uses a non-invasive method to stimulate the vagus nerve through the ear, and it operates in a closed-loop system that adjusts stimulation based on real-time physiological data, potentially offering a more personalized therapy compared to traditional methods. ^{1 2 3 10 11}

Research Team

Jeffrey Bennett, MD

Principal Investigator

Anschutz Campus - School of Medicine - Neurology

Eligibility Criteria

This trial is for individuals with Multiple Sclerosis who can attend study visits over six months. They will perform a motor task paired with vagus nerve stimulation to see if it improves their motor function.

Inclusion Criteria

I have noticeable difficulty using my dominant hand or my disability score is 2.5 or higher.

Ability to sign informed consent

Baseline grooved peg test time greater than or equal to 108 seconds for completion of the task (1 standard deviation below mean multiple sclerosis score)

Exclusion Criteria

I do not have any uncontrolled serious health issues.

Pregnancy, lactation, or lack of use of contraception

I have a history of seizures or epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham vagus nerve stimulation paired with a motor task, specifically the grooved peg test, three times weekly for the first month

4 weeks

12 visits (in-person)

Follow-up

Participants have follow-up visits to monitor motor function and disability changes at two, three, and six months

5 months

3 visits (in-person)

Treatment Details

Interventions

• Closed Loop Trans-Auricular Vagus Nerve Stimulation System
• Placebo

Trial Overview The trial tests whether stimulating the vagus nerve while doing a movement task (like the grooved peg test) is safe and helps improve motor control in people with MS, compared to sham stimulation.

Participant Groups

Group I: Experimental - Active Stimulation Experimental Treatment 1 Intervention

Participants in this arm will receive active stimulation during the paired motor task.

Group II: Control - Sham Stimulation Placebo Group 1 Intervention

Participants in this arm will receive sham stimulation during the paired motor task to create a control to the experimental group.

Closed Loop Trans-Auricular Vagus Nerve Stimulation System is already approved in United States, European Union for the following indications:

Approved in United States as Vagus Nerve Stimulation for:

• Epilepsy

Approved in European Union as Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

Vagus nerve stimulation (VNS) is an effective therapy for adults and adolescents (12 years and older) with partial onset seizures that do not respond to traditional antiepileptic medications, with over 50,000 patients having received the treatment worldwide.

In addition to epilepsy, VNS is also approved for treatment-resistant depression and shows potential for treating other medical conditions, highlighting its versatility as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. Terry, R.[2020]

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]

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]

Transcutaneous auricular vagus nerve stimulation (ta-VNS) was found to be effective in reducing symptoms of mild to moderate Crohn's disease and ulcerative colitis in a study of 22 pediatric patients, with 50% of Crohn's patients and 33% of ulcerative colitis patients achieving clinical remission by week 16.

The therapy also led to significant reductions in fecal calprotectin levels, with 64.7% of patients showing at least a 50% decrease, indicating a positive impact on inflammation without any safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial. Sahn, B., Pascuma, K., Kohn, N., et al.[2023]

Vagus nerve stimulation (VNS) is being explored as a treatment for various inflammatory conditions beyond neuropsychiatric disorders, including heart failure and rheumatoid arthritis, indicating its potential broad therapeutic applications.

The review emphasizes the importance of specific experimental parameters, such as stimulation techniques and electrode design, in optimizing VNS for effective treatment outcomes in pre-clinical studies, particularly in rodent models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations. Noller, CM., Levine, YA., Urakov, TM., 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 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]

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 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]

A novel closed-loop system for auricular vagus nerve stimulation (aVNS) was developed, which continuously monitors physiological parameters like heart rate and respiration to optimize therapy for individual patients.

The system demonstrated high precision in synchronizing aVNS stimulation with respiratory and cardiac cycles, achieving over 90% accuracy in identifying these cycles, which could lead to more effective and personalized treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular vagus nerve stimulator for closed-loop biofeedback-based operation. Dabiri, B., Zeiner, K., Nativel, A., et al.[2022]

References

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

Vagus nerve stimulation: a proven therapy for treatment of epilepsy strives to improve efficacy and expand applications. [2020]

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

Quantitative estimation of nerve fiber engagement by vagus nerve stimulation using physiological markers. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial. [2023]

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

Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations. [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. United States pubmed.ncbi.nlm.nih.gov

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

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]

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

Auricular vagus nerve stimulator for closed-loop biofeedback-based operation. [2022]