Ear Stimulation for Brain Activity

Overseen By Falon Sutton

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Seizure threshold reducers

Disqualifiers: MRI contraindications, Metal implants, Epilepsy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 30 minutes

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to explore whether stimulating different outer parts of the ear using a non-invasive form of ear stimulation called transcutaneous auricular vagus nerve stimulation (taVNS) will create different brain activation images. Investigators will recruit 24 healthy participants. The ear stimulation will be delivered while taking brain images using a magnetic resonance imaging (MRI) machine.

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 use medications that lower the seizure threshold, like olanzapine or lithium.

What data supports the effectiveness of the treatment Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)?

Research shows that taVNS is a non-invasive and cost-effective treatment that has been used to help with various conditions, including disorders of consciousness and gastric symptoms. It works by applying a small electrical current to the ear, which can influence the vagus nerve and potentially improve health outcomes. ^{1 2 3 4 5}

Is ear stimulation for brain activity safe for humans?

Ear stimulation, specifically transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe for humans. Most studies report only mild and temporary side effects like ear pain, headache, and tingling, with no severe adverse events linked to the treatment. ^{3 4 5 6 7}

How does the treatment Transcutaneous Auricular Neurostimulation (tAN) differ from other treatments for brain activity?

Transcutaneous Auricular Neurostimulation (tAN) is unique because it is a non-invasive treatment that uses low-intensity electrical currents applied to the ear to stimulate the vagus nerve, unlike other treatments that may require surgery or medication. This method is appealing due to its safety, portability, and cost-effectiveness, making it a promising alternative for various conditions without the need for invasive procedures. ^{1 3 4 8 9}

Research Team

Xiaolong Peng

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

This trial is for 24 healthy individuals interested in participating in a study to explore brain activation. Participants will undergo non-invasive ear stimulation while their brain images are taken using MRI.

Inclusion Criteria

I am between 18 and 65 years old.

I can understand and sign the consent form in English by myself.

Exclusion Criteria

I have had brain surgery in the past.

I cannot communicate in English.

I have an ear infection, skin irritation, or abnormal ear anatomy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive transcutaneous auricular vagus nerve stimulation (taVNS) at different ear sites while undergoing MRI scanning

30 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Transcutaneous Auricular Neurostimulation (tAN)

Trial Overview The study is testing the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on different outer parts of the ear and how it influences brain activity as seen on MRI scans.

Participant Groups

Group I: Auricular Neurostimulation (Active 2) Active Control 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Mastoid stimulation (15Hz stimulation of mastoid process)

Group II: Auricular Neurostimulation (Active 1) Active Control 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Cymba stimulation (15Hz stimulation of cymba conchae)

Group III: Auricular Neurostimulation (Sham 1) Placebo Group 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Sham (15Hz stimulation of the earlobe)

Transcutaneous Auricular Neurostimulation (tAN) is already approved in United States for the following indications:

Approved in United States as Transcutaneous Auricular Neurostimulation (tAN) for:

• Relief of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive treatment method that applies electrical current to the outer ear to stimulate the vagus nerve, which has been explored for its therapeutic potential in various diseases.

Over the past two decades, taVNS has gained attention as an alternative to drug treatments, but the field also faces limitations that need to be addressed for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Wang, Y., Li, SY., Wang, D., et al.[2022]

This study will investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 15 patients with a minimally conscious state, using five different frequencies (1, 10, 25, 50, and 100 Hz) to determine the optimal stimulation parameters.

The goal is to achieve stable improvements in consciousness levels in patients with disorders of consciousness by optimizing the taVNS neuromodulation technique, with results measured through the coma recovery scale-revised (CRS-R) and resting EEG assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. Zhai, W., Jiao, H., Zhuang, Y., 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]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and well-tolerated method for treating conditions like drug-resistant epilepsy, but a recent randomized double-blind trial found no significant difference in outcomes between high- and low-stimulation groups.

The most common side effect of taVNS is a tingling sensation or pain at the stimulation site, and while it shows promise, further research is needed to fully understand its efficacy and to potentially gain approval for insurance coverage in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. Yamamoto, T.[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]

The study demonstrates that millimeter wave (MMW) stimulation can selectively activate the auricular branch of the vagus nerve (ABVN) without affecting nearby non-vagal nerves, as shown by significant increases in local field potential (LFP) power in the nucleus tractus solitarii (NTS) during targeted stimulation.

In contrast, non-vagal nerve stimulation resulted in decreased LFP power, indicating that MMW can effectively differentiate between vagal and non-vagal responses, paving the way for a new clinical treatment approach for conditions like depression and epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. Song, HY., Shin, DW., Jung, SM., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) is a promising non-invasive alternative to traditional vagus nerve stimulation (VNS) for treating conditions like epilepsy and depression, which can be invasive and have side effects.

There is ongoing research into the best stimulation parameters and sites for tVNS, particularly focusing on stimulation at the outer ear, to optimize its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. Hilz, MJ., Bolz, A.[2022]

References

1. Singapore pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. [2023]

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

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

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

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

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

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. [2022]

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

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. [2022]