Vagus Nerve Stimulation for Physiological Response Study

Overseen By Rodney W Roosevelt, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Arkansas Tech University

Must not be taking: Stimulants, Caffeine, Nicotine

Disqualifiers: Mood disorders, Drug use, others

Compensation: Varies

Number of Visits: 1

Duration: 1 hour

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how stimulating the vagus nerve through the ear using Transdermal Vagus Nerve Stimulation (tVNS) might affect brain activity and eye response, potentially impacting various health conditions. Participants will experience different levels of stimulation, including some without real stimulation, to compare outcomes. It is ideal for individuals who are generally healthy and do not regularly use mood-altering substances or stimulants like caffeine or nicotine. As an unphased trial, this study allows participants to contribute to groundbreaking research that could lead to significant health advancements.

Will I have to stop taking my current medications?

The trial excludes participants who use prescription and non-prescription drugs, including stimulants like caffeine and nicotine, so you may need to stop taking these if you want to participate.

What prior data suggests that transdermal vagus nerve stimulation is safe?

Studies have shown that transdermal vagus nerve stimulation (tVNS) on the ear is generally safe. Research involving many participants identified mild skin irritation at the electrode site as the most common side effect, occurring in about 18% of people. Less common side effects included headaches in about 4% of participants and cold-like symptoms, such as a sore throat or runny nose, in about 2%.

Overall, the treatment's side effects are usually mild and resolve on their own. Studies have found no serious side effects, indicating that tVNS is generally well-tolerated and considered safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Vagus Nerve Stimulation for Physiological Response because it explores a unique approach to influencing the body's physiological responses. Unlike medications that typically target specific symptoms, this method uses transdermal vagus nerve stimulation (tVNS) to potentially modulate the nervous system directly through the skin. This non-invasive technique could offer a new way to manage conditions by harnessing the body's natural pathways, reducing the need for more invasive procedures or medications with significant side effects. By focusing on nerve stimulation, this trial may uncover new insights into treating various health issues with greater precision and fewer complications.

What evidence suggests that transdermal vagus nerve stimulation is effective for altering physiological responses?

Research has shown that using a device on the skin to stimulate the vagus nerve can positively affect brain function. In this trial, participants may receive different types of transdermal vagus nerve stimulation (tVNS), including active stimulation, sham stimulation, or nonstimulation. One study found that this method improved thinking and performance, especially in tasks requiring self-control. Another study showed that it activated parts of the brain that help balance its activity, which might be beneficial for treatment. Additionally, it improved sleep quality in people with insomnia and reduced related symptoms. These findings suggest that this technique could change brain activity and potentially help with various conditions. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18 or older. It's not suitable for those with mood disorders or who use stimulants, including everyday substances like caffeine and nicotine.

Exclusion Criteria

I use prescription, non-prescription drugs, caffeine, or nicotine.

I have been diagnosed with a mood disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo non-invasive vagus nerve stimulation or placebo for a single session

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transdermal Vagus Nerve Stimulation (tVNS)

Trial Overview

The study tests if non-invasive vagus nerve stimulation (tVNS) at the ear can change brain activity and pupil size, which could have implications for both science and potential treatments.

How Is the Trial Designed?

Group I: Active Stimulation 0.5 Experimental Treatment 1 Intervention

0.5mA, 30Hz intermittent transdermal vagus nerve stimulation of the auricle vagus. Stimulation 30 second on/30 seconds off for five cycles.

Group II: Nonstimulation Placebo Group 1 Intervention

Placement of electrode without any stimulation.

Group III: Sham Stimulation Placebo Group 1 Intervention

0.5mA, 5Hz intermittent transdermal vagus nerve stimulation of the auricle vagus. Stimulation 30 second on/30 seconds off for five cycles.

Group IV: Lobe Control Placebo Group 1 Intervention

0.5mA, 30Hz intermittent transdermal vagus nerve stimulation of the earlobe. Stimulation 30 second on/30 seconds off for five cycles.

Who Is Running the Clinical Trial?

Arkansas Tech University

Lead Sponsor

Trials

2

Recruited

160+

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]

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]

Transcutaneous low-level vagus nerve stimulation (tVNS) in 15 male volunteers showed significant reductions in left ventricular contractility and output, indicating a potential for cardiac autonomic modulation.

While tVNS reduced heart workload, it also led to increased blood pressure and total peripheral resistance, suggesting a reflex response that needs further investigation to understand its therapeutic implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation. Sinkovec, M., Trobec, R., Meglic, B.[2021]

Transcutaneous vagus nerve stimulation (tVNS) is gaining interest for its non-invasive application in research and clinical settings, but there is a need for better reporting practices to ensure safety and comparability across studies.

The review proposes a set of minimal reporting items for future tVNS studies, including technical details, participant criteria, and outcome measures, to enhance the reliability and effectiveness of this therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020). Farmer, AD., Strzelczyk, A., Finisguerra, A., 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]

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., 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]

Repeated vagal nerve stimulation (VNS) in rats showed significant antidepressant and anxiolytic effects, comparable to the effects of standard antidepressants desipramine and sertraline, as measured by behavioral tests.

The antidepressant effects of VNS were found to depend on serotonergic nerve activity, while noradrenergic nerves also contributed to its anxiolytic effects, indicating a complex mechanism of action for VNS in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats. Furmaga, H., Shah, A., Frazer, A.[2022]

Citations

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Specifically, the high-frequency group experienced a 25% reduction in seizures, while the low-frequency group's seizures decreased by 6%.

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frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00284/full

Critical Review of Transcutaneous Vagus Nerve Stimulation

This review presents the current status of tVNS with a focus on stimulation parameters, stimulation sites, and available devices.

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The effects of non-invasive transcutaneous auricular vagus ...

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Transcutaneous Auricular Vagus Nerve Stimulation for ...

Previous studies have demonstrated that taVNS cannot only effectively improve sleep quality in patients with insomnia, but also alleviate accompanying symptoms ...

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The most common side effects were: local skin irritation from electrode placement (240 participants, 18.2%), headache (47, 3.6%) and nasopharyngitis (23, 1.7%).

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nature.com

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Safety of transcutaneous auricular vagus nerve stimulation ...

Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet ...

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Safety. No major side effects or bad experiences were found in the study. Only two participants (both in the ta-VNS group) reported skin redness ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11841445/

A pooled analysis of the side effects of non-invasive ...

These findings demonstrate a favorable safety profile of taVNS, with mostly mild and transient effects, supporting its use as a suitable non-invasive tool.