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

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This study investigates the capacity of non-invasive vagus nerve stimulation, applied at the ear, to alter to measures of locus coeruleus output pupil diameter and EEG alpha power. Non-invasive alteration in locus coeruleus output is of interest in regard to basic science and has potential clinical implications in a number of conditions.

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 data supports the effectiveness of this treatment?

Research suggests that transcutaneous vagus nerve stimulation (tVNS) may help with various neurological and psychiatric conditions due to its non-invasive nature and good safety profile. It has shown potential in both adults and pediatric patients, with studies indicating it could be effective for conditions like depression and anxiety. ^{1 2 3 4 5}

Is transcutaneous vagus nerve stimulation (tVNS) safe for humans?

Transcutaneous vagus nerve stimulation (tVNS) is generally considered safe for humans, with only mild and temporary side effects like ear pain, headache, and tingling. There is no evidence of serious adverse effects, making it a safe option for clinical use. ^{2 4 6 7 8}

How is transdermal vagus nerve stimulation (tVNS) different from other treatments?

Transdermal vagus nerve stimulation (tVNS) is unique because it is a non-invasive method that stimulates the vagus nerve through the skin, unlike traditional methods that require surgical implantation. This makes it safer, more affordable, and easier to use, especially for children and those who prefer non-surgical options. ^{1 2 4 7 9}

Eligibility Criteria

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.

Inclusion Criteria

I am 18 or older and in good health.

Exclusion Criteria

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

I have been diagnosed with a mood disorder.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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) 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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects. [2021]

4. 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]

5. United States 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

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