Vagus Nerve Stimulation for Healthy Subjects

Overseen By Gabriel Gonzalez, DPT

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Miami

Must not be taking: Buprenorphine

Disqualifiers: Chronic pain, Unstable medical condition, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two types of gentle electrical stimulation on the ear might affect comfort and tolerability. The study will test both biphasic and monophasic forms of stimulation, which have different wave patterns. Participants will help researchers understand the sensations and effectiveness of these treatments. English speakers without chronic pain or unstable medical conditions might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to innovative research and potentially improve future treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking Buprenorphine or have stopped taking it within the last month.

What prior data suggests that this method is safe for healthy subjects?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. This treatment, in both forms, typically causes only mild and short-lasting side effects. Studies suggest that taVNS is a safe and non-invasive method. It has been used to help with conditions like epilepsy and to improve cognitive function, without major safety concerns. Although the FDA has not yet approved it for any specific condition, the evidence so far supports its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments being studied in vagus nerve stimulation (VNS) for healthy subjects because these techniques offer a non-invasive way to potentially harness the power of the nervous system for various therapeutic benefits. Unlike traditional treatments that might involve medication or surgical procedures, biphasic and monophasic transcutaneous auricular VNS deliver electrical stimulation through the skin of the outer ear, targeting the vagus nerve. This novel delivery method is particularly interesting because it could modulate nerve activity without the risks associated with more invasive procedures. By exploring these distinct stimulation patterns, researchers hope to uncover new insights into how VNS can be optimized for therapeutic use.

What evidence suggests that this trial's treatments could be effective for vagus nerve stimulation?

Research has shown that stimulating the vagus nerve through the skin of the ear, known as transcutaneous auricular vagus nerve stimulation (taVNS), can affect heart rate variability, a sign of a healthy heart. Notably, 86% of studies have found significant effects on heart rate variability in healthy individuals. In this trial, participants will receive either biphasic taVNS, which can improve brain functions like focus and attention, or monophasic taVNS, which may aid memory and learning by activating certain parts of the nervous system. Both types of taVNS might also lower heart rate during exercise, promoting calmness without significantly altering blood pressure. ^{2 6 7 8 9}

Who Is on the Research Team?

Marlon Wong, PT, PhD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for healthy English-speaking adults aged 18-80 who can consent and complete interviews in English. It's designed to see how comfortable and effective different types of gentle electrical ear stimulation are.

Inclusion Criteria

I can speak English and consent to interviews in English.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive transcutaneous auricular vagus nerve stimulation (taVNS) with different waveforms to assess comfort and tolerability

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Biphasic transcutaneous auricular vagus nerve stimulation
• Monophasic transcutaneous auricular vagus nerve stimulation

Trial Overview The study tests two kinds of transcutaneous auricular vagus nerve stimulation (taVNS): monophasic and biphasic. Participants will experience these mild electrical waves through the ear to determine comfort levels and effectiveness.

How Is the Trial Designed?

Group I: Biphasic followed by monophasic taVNS group Experimental Treatment 2 Interventions

Participants in the group "Biphasic followed by monophasic taVNS" will be in this group for up to 6 hours.

Group II: Monophasic followed by biphasic taVNS group Active Control 2 Interventions

Participants in the group "monophasic followed by biphasic" will be in this group for up to 6 hours.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

Vagus nerve stimulation (VNS), particularly through non-invasive methods like transcutaneous VNS (tVNS), shows promise for treating various clinical disorders, including heart failure and migraines, by stimulating the auricular branch of the vagus nerve without the need for surgical implantation.

Current research highlights the need for more detailed studies on the neuroanatomy of the auricular branch of the vagus nerve (ABVN) to better understand its therapeutic effects and optimize stimulation parameters, as existing literature lacks consensus on the most effective stimulation sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anatomical basis for transcutaneous auricular vagus nerve stimulation. Butt, MF., Albusoda, A., Farmer, AD., et al.[2022]

Tactile stimulation at the auricular branch of the vagus nerve using air pressure significantly enhances parasympathetic activity, as evidenced by changes in heart rate and heart rate variability metrics in 22 healthy participants.

The study found significant differences in heart rate and heart rate variability between baseline and stimulation periods, suggesting that this method could have potential clinical applications, although further research is needed to optimize stimulation parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory Investigation of the Effects of Tactile Stimulation Using Air Pressure at the Auricular Vagus Nerve on Heart Rate Variability. Lee, HJ., Wi, S., Park, S., 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]

Acupuncture at the auricular branch of the vagus nerve (ABVN) significantly reduced heart rate by approximately 4%-6% and increased heart rate variability (HRV) as measured by SDNN by about 19% in a study of 24 healthy male volunteers.

These results suggest that ABVN acupuncture may activate the parasympathetic nervous system, although the overall effects on other HRV parameters were modest and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acupuncture at the auricular branch of the vagus nerve enhances heart rate variability in humans: An exploratory study. Boehmer, AA., Georgopoulos, S., Nagel, J., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) showed significant effects on heart rate variability in healthy individuals, with 86% of studies reporting improvements in standard deviation of NN intervals and other heart rate metrics.

Baroreflex sensitivity results were less consistent, with only one out of six studies showing significant changes, indicating that the effectiveness of taVNS may vary based on individual autonomic function and the need for standardized study designs in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the effects of transcutaneous auricular vagus nerve stimulation on baroreflex sensitivity and heart rate variability in healthy subjects. Soltani, D., Azizi, B., Sima, S., et al.[2023]

Noninvasive transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) significantly reduces spontaneous ventricular arrhythmias in beagle dogs after myocardial infarction, indicating its potential as an antiarrhythmic treatment.

AB-VNS enhances ventricular electrical stability and reduces ventricular interstitial fibrosis, although it does not improve overall cardiac function or reverse structural changes in the heart after 4 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. Nasi-Er, BG., Wenhui, Z., HuaXin, S., et al.[2019]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12113213/

Investigation of the Effectiveness of Transcutaneous Auricular ... The aim of our study was to investigate the effect of transcutaneous auricular VNS (taVNS) on the vestibular symptoms of unilateral vestibular hypofunction ( ...

2. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1549167/full

Effects of off-line auricular transcutaneous vagus nerve ... In this pilot study we investigated the effects of a taVNS off-line stimulation paradigm over a digit span task in healthy volunteers. Our ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666956025000364

Exploring the impact of transcutaneous vagus nerve ... Active tVNS resulted in partly accelerated neural processing in the context of response inhibition in both groups and enhanced EF performance in subjects ...

4. nature.com nature.com/articles/s41598-024-72179-4

Evaluating phasic transcutaneous vagus nerve stimulation ... Phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals.

5. withpower.com withpower.com/trial/phase-healthy-subjects-hs-10-2024-946e7

Vagus Nerve Stimulation for Healthy Subjects Transcutaneous auricular vagus nerve stimulation (taVNS) showed significant effects on heart rate variability in healthy individuals, with 86% of studies ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772204/

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07090668

Trans-auricular Vagal Nerve Stimulation as an Innovative ... The goal of this study is to evaluate the effects of transauricular vagal nerve stimulation on the treatment of pain in children with Sickle Cell Disease.

8. nature.com nature.com/articles/s41598-021-87032-1

Transcutaneous auricular vagus nerve stimulation induces ... taVNS is a novel non-invasive brain stimulation technique considered as a potential supplementary treatment option for subjects with refractory epilepsy.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1566070225000803

Symmetric projection attractor reconstruction Here, we examined the neuromodulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) – a non-invasive brain stimulation tool – on autonomic ...