Auricular Stimulation for Healthy Subjects

(NIRAS Trial)

Overseen By Amy Monroe, MPH, MBA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Opioids, Marijuana, Psychoactives, others

Disqualifiers: Chronic pain, Neuropathy, Substance abuse, others

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

Compensation: Varies

Number of Visits: 1

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use opioids, marijuana, or psychoactive prescription medications regularly. If you are using these, you would need to stop before participating.

What data supports the effectiveness of the treatment Auricular Stimulation for healthy subjects?

Research shows that auricular stimulation, like auricular acupuncture, can help reduce body weight in both mildly obese and healthy individuals. Additionally, auricular stimulation has been found effective in reducing preoperative anxiety and managing chronic pain, suggesting it may have broader benefits for health and well-being. ^{1 2 3 4 5}

Is auricular stimulation generally safe for humans?

The research articles provided do not contain specific safety data on auricular stimulation, but they discuss cardiac monitoring and arrhythmias in healthy volunteers during drug trials. These studies highlight the importance of monitoring heart rhythms, as some arrhythmias can occur even in healthy individuals, but they do not directly address the safety of auricular stimulation. ^{6 7 8 9 10}

How does auricular stimulation differ from other treatments for cardiovascular conditions?

Auricular stimulation is unique because it involves non-invasive electrical stimulation of the ear's vagus nerve, which can influence heart function without the need for surgery. This method offers a simpler and potentially more cost-effective alternative to traditional vagus nerve stimulation, which typically requires a surgical procedure. ^{1 11 12 13 14}

What is the purpose of this trial?

This is a single-visit non-invasive study of healthy volunteer subjects. Brain activity will be measured with infra-red light sensors attached to a cap worn on the head, while both ears are gently stimulated with plastic filaments.

Research Team

Keith Vogt, MD, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This clinical trial is open to healthy volunteers who want to participate in a single-visit study. There are no specific inclusion or exclusion criteria provided, which suggests that the trial may have broad eligibility.

Exclusion Criteria

I have active skin issues on one or both ears.

History of substance misuse/abuse

Current or recent (<1 month) opioid or marijuana use

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Single-visit Study

Participants undergo a single session where brain activity is measured using fNIRS while auricular points are stimulated

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate adverse effects post-study

1 week

Treatment Details

Interventions

• Auricular Stimulation

Trial Overview The study is testing how brain activity responds to auricular stimulation (gentle stimulation of both ears with plastic filaments) while measuring it using Near-InfraRed Spectroscopy sensors attached to a cap.

Participant Groups

Group I: Auricular stim with fNIRS Experimental Treatment 1 Intervention

Points on the ear that correspond to the the shoulder, thumb, and lumbar spine (within an accepted cartography for auriculotherapy) will be stimulated repeatedly with flexible plastic (von Frey) filaments. A functional near-infrared spectroscopy cap will be worn, and brain responses to the stimulation will be recorded.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Findings from Research

Auricular stimulation (AS) has been shown to significantly reduce heart rate (HR) and alter heart rate variability (HRV) by decreasing the LF/HF ratio, indicating increased vagal activity, based on a systematic review of 78 trials.

The reduction in HR from AS is considered clinically safe, with only minor side effects reported, suggesting potential for further research into its use for managing conditions like tachycardia or autonomic imbalance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials. Hua, K., Cummings, M., Bernatik, M., et al.[2023]

Auricular stimulation (AS) significantly reduces preoperative anxiety scores compared to sham controls and no intervention, based on a systematic review of 15 studies involving 1603 patients, indicating its potential effectiveness in managing anxiety before surgery.

There were no serious adverse effects reported from AS, suggesting it is a safe option; however, its efficacy is comparable to benzodiazepines, and further research is needed to confirm its benefits due to varying levels of evidence quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular stimulation for preoperative anxiety - A systematic review and meta-analysis of randomized controlled clinical trials. Usichenko, TI., Hua, K., Cummings, M., et al.[2022]

In a study of 156 healthy volunteers undergoing 24-hour ambulatory cardiac monitoring, only 13% showed normal sinus rhythm, highlighting a significant prevalence of cardiac abnormalities in this population.

The most common finding was supraventricular ectopics (83%), with other issues like ventricular ectopics and sinus pauses also noted, suggesting the need for clear guidelines to evaluate cardiac health before trials of new drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of 24 h ambulatory ECG recordings in the assessment of new chemical entities in healthy volunteers. Stinson, JC., Pears, JS., Williams, AJ., et al.[2020]

Digoxin is effective for controlling ventricular rate in patients with chronic atrial fibrillation, especially when combined with beta-blockers or calcium channel antagonists, but is less effective as a standalone treatment during exercise.

While digoxin is generally considered safe for patients with atrial fibrillation, its safety profile may not be fully understood due to limited studies, particularly in patients with heart failure, and potential adverse effects like cardiac arrhythmias should be monitored closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of digoxin as a pharmacological treatment of atrial fibrillation. Tamargo, J., Delpón, E., Caballero, R.[2019]

A comprehensive database of 396,985 drug-related cardiac adverse effects (AEs) linked to 1,632 approved drugs was created, revealing significant clusters of AEs affecting heart function, such as arrhythmias and heart failure.

The study identified that cardiac AEs are highly correlated with drugs targeting cardiovascular functions and specific mechanisms of action, including interactions with various receptors like alpha- and beta-adrenergic receptors, which may help predict and understand these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence. Matthews, EJ., Frid, AA.[2013]

Auricular vagal nerve stimulation (AVNS) is a promising neuromodulation technique with potential therapeutic applications, but its mechanisms of action may involve more complex neural networks than previously thought, including connections beyond the auricular branch of the vagus nerve.

The review highlights the importance of understanding the intricate anatomy and neural connections in the auricular region, which could lead to improved interpretations of AVNS research and better future studies in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concerning Auricular Vagal Nerve Stimulation: Occult Neural Networks. Cakmak, YO.[2020]

The auricular branch of the vagus nerve (ABVN), located in the ear, has potential for non-invasive electrical stimulation to improve heart function, offering a simpler alternative to traditional vagus nerve stimulation (VNS) that requires surgery.

This review highlights the growing interest and evidence supporting the use of ABVN stimulation as a cost-effective method for modulating cardiac activity, which could lead to new treatment options for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. Murray, AR., Atkinson, L., Mahadi, MK., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of auricular stimulation -a systematic review and meta-analysis of randomized controlled clinical trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Auricular therapy for chronic pain management in adults: A synthesis of evidence. [2022]

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

Auricular stimulation for preoperative anxiety - A systematic review and meta-analysis of randomized controlled clinical trials. [2022]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical and experimental analysis of the use of the Analgedent electrostimulator for dental analgesia]. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Effects of bilateral auricular acupuncture stimulation on body weight in healthy volunteers and mildly obese patients. [2019]

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

Arrhythmias Seen in Baseline 24-Hour Holter ECG Recordings in Healthy Normal Volunteers During Phase 1 Clinical Trials. [2020]

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

Use of 24 h ambulatory ECG recordings in the assessment of new chemical entities in healthy volunteers. [2020]

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

Cardiovascular Monitoring in Normal Healthy Adults: A Literature Review and Recommendations for the Reporting of Disturbances of Cardiac Rhythm. [2019]

9. England pubmed.ncbi.nlm.nih.gov

The safety of digoxin as a pharmacological treatment of atrial fibrillation. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence. [2013]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Concerning Auricular Vagal Nerve Stimulation: Occult Neural Networks. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. [2018]

13. France pubmed.ncbi.nlm.nih.gov

Norepinephrine and acetylcholine changes during electrically-induced atrial fibrillation episodes in canine models. [2017]

14. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of auricular vagus nerve stimulation on electroencephalography and electromyography measurements in healthy persons. [2023]