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

30 Participants Needed

Trial Summary

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 data supports the idea that Vagus Nerve Stimulation in Healthy Subjects is an effective treatment?

The available research shows that transcutaneous vagus nerve stimulation (tVNS) is a promising treatment for various conditions. It is non-invasive, meaning it doesn't require surgery, and is less expensive compared to other methods. Studies have shown that tVNS can help with conditions like epilepsy, depression, and headaches, including migraines. It works by affecting the nervous system, which can lead to improvements in heart rate and mood. Additionally, it has been found to be safe and well-tolerated, even in children. This makes it a good alternative to more invasive treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Vagus Nerve Stimulation in healthy subjects?

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive treatment that has shown promise in treating various conditions like epilepsy, depression, and migraines. It is considered safe and well-tolerated, with potential applications in both adults and children for a range of physical and mental health issues. ^{1 2 3 4 6}

What safety data exists for vagus nerve stimulation?

Vagus nerve stimulation (VNS), particularly the non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe. A systematic review and meta-analysis of 177 studies involving 6322 subjects found that taVNS has a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, with no severe adverse events linked to the treatment. Non-invasive VNS systems, which do not require surgery, improve safety and tolerability compared to surgically implanted VNS. These findings support the use of taVNS as a safe and feasible option for clinical intervention. ^{1 2 3 7 8}

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation, especially the non-invasive transcutaneous method, is generally considered safe with only mild and temporary side effects like ear pain, headache, and tingling. Serious adverse effects are rare, and the non-invasive approach avoids the risks associated with surgical implantation. ^{1 2 3 7 8}

Is the treatment ABVN stimulation a promising treatment?

Yes, ABVN stimulation, also known as transcutaneous vagus nerve stimulation (tVNS), is a promising treatment. It is non-invasive, meaning it doesn't require surgery, and is considered safe and affordable. It has potential benefits for treating various health conditions, including those affecting the brain and body. Additionally, it is portable, making it convenient for future use. ^{1 2 3 6 9}

How is the treatment ABVN stimulation different from other treatments for this condition?

ABVN stimulation, also known as transcutaneous vagus nerve stimulation (tVNS), is unique because it is a non-invasive method that stimulates the vagus nerve through the skin, specifically targeting the ear or neck area. Unlike traditional vagus nerve stimulation, which requires surgical implantation, tVNS is safe, portable, and does not involve surgery, making it more accessible and easier to use. ^{1 2 3 6 9}

What is the purpose of this trial?

The vagus nerve is a largely-internal nerve that controls many bodily functions, including stomach function. Investigators hope that electrically stimulating the nerve around the external ear will also stimulate the internal vagus nerve. If it does, then investigators hope that this will help the treatment of patients with nausea and vomiting and disordered stomach function. Investigators also hope to be able to measure the activity of the vagus nerve when it is stimulated in other ways. This could help investigators learn more about studying this nerve in the future.

Research Team

Thomas Nowak, MD

Principal Investigator

Indiana University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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) 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 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]

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 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]

References

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

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

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

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]

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

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020). [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cardiovascular responses to low-level transcutaneous vagus nerve stimulation. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

9. Switzerland 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. [2023]