Vagus Nerve Stimulation in Healthy Subjects

(ABVN1 Trial)

Overseen By Maureen Schilling

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Must not be taking: Gastric motility drugs

Disqualifiers: Gastric motility issues, Pregnancy, Prisoners, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how stimulating the vagus nerve, a key nerve affecting stomach function, might help treat nausea and vomiting. Researchers are testing whether electrical stimulation on the nerve near the external ear can also affect the internal vagus nerve. This approach seeks to enhance understanding of the nerve's function and future measurement methods. Healthy individuals willing to have electrodes placed in their external ear and perform certain maneuvers are encouraged to participate. As an unphased trial, this study offers participants the chance to contribute to foundational research that could lead to new treatments for nausea and vomiting.

Do I need to stop taking my current medications for this trial?

Yes, if you are taking medications that affect gastric motility, you cannot participate in this trial.

Do I need to stop my current medications for the trial?

If you are taking medications that affect stomach movement, you may need to stop them to participate in this trial.

What prior data suggests that this vagus nerve stimulation is safe for healthy subjects?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. In past studies, most side effects were mild and temporary, indicating that people usually tolerate the treatment well.

The device for this stimulation is non-invasive, as it does not involve surgery. It works by sending electrical signals through the skin. Previous studies using this method have demonstrated its safety, with few serious side effects.

The FDA has already approved vagus nerve stimulation, including methods like taVNS, for treating conditions such as depression and epilepsy. This approval suggests a level of safety for similar methods, such as ABVN stimulation.

Overall, the evidence indicates that ABVN stimulation is a safe option for those considering participation in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about vagus nerve stimulation because it explores a novel approach that goes beyond traditional drug therapies. Most treatments rely on medications to manage symptoms, but this technique uses electrical stimulation of the vagus nerve, which is thought to influence brain activity and improve various bodily functions. This non-invasive method could offer a unique alternative or complement to existing treatment options by potentially enhancing mental and physical health through direct nerve activation.

What evidence suggests that vagus nerve stimulation is effective for nausea and vomiting?

Research has shown that stimulating the vagus nerve can help treat conditions like depression and epilepsy. The FDA has approved this treatment for these uses. Studies have found that transcutaneous auricular vagus nerve stimulation (taVNS), which stimulates the nerve through the skin of the ear, can influence brain activity and improve some body functions, such as mood and sleep. Recent research suggests it might also help with stomach issues, like nausea, by regulating stomach function. This trial will explore the effects of vagus nerve stimulation in healthy subjects, making it a promising area for understanding its potential benefits. ^{1 4 5 6 7}

Who Is on the Research Team?

Thomas Nowak, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for healthy volunteers aged 18-80 who are willing to have electrodes placed on their external ear and perform vagal maneuvers. It's not suitable for those unable to consent, pregnant women, prisoners, or individuals with gastric motility issues or on related medications.

Inclusion Criteria

I am willing to do a specific exercise to test my nerve function.

You are a person who is generally healthy and not currently experiencing any medical issues.

I am willing to have electrodes placed in my external ear.

Exclusion Criteria

Prisoners

You have problems with how your stomach moves, as determined by the study doctor or another doctor involved in the study.

You are pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ear Stimulation Group

Participants undergo a one-time visit for baseline and test procedures involving transcutaneous stimulation of the auricular branch of the vagus nerve.

1 visit

1 visit (in-person)

Vagal Maneuver Group

Participants undergo various vagal maneuvers to measure vagal response, potentially over multiple visits.

1-2 visits

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedures.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABVN stimulation
• Vagal Maneuvers

Trial Overview The study tests if stimulating the vagus nerve at the ear can affect stomach function. One method uses transcutaneous auricular stimulation; another involves performing specific maneuvers that activate the vagus nerve.

How Is the Trial Designed?

Group I: Healthy Subjects Experimental Treatment 2 Interventions

Healthy volunteers aged 18-80 years old who will undergo vagus nerve stimulation.

ABVN stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Vagus Nerve Stimulation for:

• Epilepsy
• Treatment-resistant depression
• Stroke rehabilitation

Approved in European Union as Vagus Nerve Stimulation for:

• Epilepsy
• Treatment-resistant depression

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Purdue University

Collaborator

Trials

239

Recruited

72,200+

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]

Transcutaneous cervical vagus nerve stimulation (tcVNS) significantly increased motor cortex excitability in healthy adults, as evidenced by a notable increase in motor-evoked potential (MEP) amplitude after real stimulation compared to sham stimulation.

The study involved 28 healthy participants and demonstrated that real tcVNS not only increased MEP amplitude but also decreased MEP latency, indicating a faster response time in the motor cortex, while no significant changes were observed in the resting motor threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study. Wang, MX., Wumiti, A., Zhang, YW., et al.[2023]

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]

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 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 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) effectively increases heart rate variability (HRV), indicating a shift towards parasympathetic dominance, with the most significant effects observed at the cymba conchae and fossa triangularis targets.

The study found that HRV increases in a charge-dependent manner, with optimal stimulation parameters being bursts of taVNS at a pulse duration of 100 μs and a current intensity of 2 mA, suggesting these parameters are both comfortable and effective for enhancing HRV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets. Machetanz, K., Berelidze, L., Guggenberger, R., et al.[2021]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7199464/

Critical Review of Transcutaneous Vagus Nerve Stimulation Vagus nerve stimulation (VNS) is an FDA-approved treatment for both pharmacoresistant depression and epilepsy and can produce clinically ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1566070222000972

Review Transcutaneous vagus nerve stimulation - A brief ... Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07080749

The Effect of Vagus Nerve Stimulation on Pain and ... This study compares the effectiveness of these two intervention methods with a control group that receives no treatment during the study period.

4. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1693907/full

Transcutaneous auricular vagus nerve stimulation in ... taVNS could regulate brain activity, motor and mental functions, and autonomic nervous system activity in patients with stroke and Parkinson's ...

5. aging-us.com aging-us.com/article/102074/text

Effects of transcutaneous vagus nerve stimulation in ... Two weeks of daily tVNS improved measures of autonomic function, and some aspects of QoL, mood and sleep.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06009159

Vagus Nerve Stimulation(VNS) As Treatment For ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... tVNS (transcutaneous VNS) via auricular branches of vagus nerve (ABVN). The ...

7. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1539416/full

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.