Ear Stimulation for Brain Activity

Overseen By Bashar W Badran, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Olanzapine, Chlorpromazine, Lithium, others

Disqualifiers: Seizure, Epilepsy, Psychosis, Mania, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new type of ear stimulation, Transcutaneous Auricular Neurostimulation (tAN), to assess its effects on brain activity. The focus is on stimulating two specific nerves in the ear to determine if this has a greater impact than stimulating just one nerve. Participants will have electrodes placed on their ears during a brain scan. The study seeks adults who can provide their own consent and do not have conditions such as frequent severe headaches or a history of brain surgery.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research in brain stimulation techniques.

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, chlorpromazine, or lithium.

What prior data suggests that this neurostimulation technique is safe?

Research has shown that transcutaneous auricular neurostimulation (tAN) is generally safe for people. Studies have found that tAN is usually well-tolerated, with only mild and short-lasting side effects in some cases. One study found it to be a safe and effective way to reduce symptoms for certain conditions, leading to FDA approval for those uses. Another study reported that tAN is practical and safe for use in hospitals for patients with specific needs. Overall, evidence suggests that tAN is a safe option for participants in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the ear stimulation technique, known as transauricular vagus nerve stimulation (tAN), because it offers a non-invasive approach to modulating brain activity. Unlike traditional treatments for brain disorders that might involve medications or invasive procedures, tAN uses electrical stimulation through electrodes placed on specific parts of the ear. This method could potentially target brain activity with fewer side effects and greater precision. Additionally, the various stimulation patterns being tested—such as different frequencies and ear targets—might offer tailored options for individuals, enhancing the effectiveness of treatment. Overall, tAN represents a promising direction for personalized and less intrusive brain therapy.

What evidence suggests that this trial's treatments could be effective for brain activity?

Research shows that transcutaneous auricular neurostimulation (tAN), which stimulates nerves near the ear, can alter brain signals. Studies have found that tAN reduces pain and alleviates symptoms of opioid withdrawal. Clinical tests have confirmed its safety and effectiveness for these purposes. Additionally, tAN enhances certain brain activities, particularly in the frontal region. This trial will explore various forms of tAN, including active and sham stimulation, to assess its potential benefits for brain health and function. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-65 who can consent to participate. It's not suitable for those with frequent/severe headaches, contraindications for MRI, untreated medical/neurological/psychiatric conditions, psychosis or mania history, metal implants in head/heart/neck, brain surgery or heart issues history, seizure risk factors like family history or certain medications use, significant head injury history, substance abuse problems or if pregnant.

Inclusion Criteria

I can make my own medical decisions and sign consent forms.

Exclusion Criteria

I often have severe headaches.

I have had a serious head injury or concussion in the past.

I have had a heart attack or irregular heartbeat.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo a one-visit, randomized, double-blind, sham-controlled trial involving transcutaneous auricular neurostimulation (tAN) during fMRI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• tAN

Trial Overview

The study tests the effects of transcutaneous auricular neurostimulation (tAN) on two cranial nerves during an fMRI scan. Participants will be randomly assigned to receive tAN targeting different nerve combinations (vagus nerve alone, trigeminal branch alone, both together) versus a sham (fake stimulation), to see which has greater neurological impact.

How Is the Trial Designed?

Group I: Auricular Neurostimulation (Active 3) 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 -Combo stimulation (stimulation of both the 15Hz cymba conchae and 100HZ tragus)

Group II: 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 -ATNS Only stimulation (100Hz stimulation of the tragus)

Group III: 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 -ABVN Only stimulation (15Hz stimulation of cymba conchae)

Group IV: 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)

Group V: Auricular Neurostimulation (Sham 2) 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 (100Hz stimulation of the earlobe)

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Auricular stimulation can trigger acute pupillary responses (PRs), indicating that it may activate noradrenergic pathways in the brain, which are important for therapeutic effects.

The study involved 19 participants and found that higher pulse amplitudes and frequencies led to stronger and quicker pupillary responses, particularly when stimulating the canal area of the ear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans. Urbin, MA., Lafe, CW., Simpson, TW., et al.[2021]

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]

In a study involving 50 young adults, transcutaneous auricular nerve stimulation (taNS) at 130 µA significantly decreased cardiac output, with distinct gender-related responses observed: women experienced a drop in heart rate, while men showed reductions in stroke volume and contractility.

The findings suggest that the taNS protocol may have potential for modulating cardiac autonomic responses, but further research is needed to explore its therapeutic applications in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers. Šinkovec, M., Trobec, R., Kamenski, T., 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) 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 electrical stimulation of the anterior part of the left outer auditory canal effectively activates specific vagal afferents, as indicated by significant decreases in BOLD signals in key brain regions associated with the vagus nerve, suggesting a targeted method for CNS stimulation.

In contrast, stimulation of the posterior part of the auditory canal resulted in less specific changes in brain activity, indicating that the anterior stimulation may be more effective for therapeutic applications in psychiatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study. Kraus, T., Kiess, O., Hösl, K., et al.[2016]

Transcutaneous electrical nerve stimulation (TENS) applied to the auricula significantly reduced tinnitus severity and associated anxiety and stress levels in a study of 60 patients, with results showing a notable difference compared to a placebo group.

Both one-ear and two-ear TENS treatments were effective, but there was no significant difference in efficacy between the two methods, indicating that TENS can be a viable treatment option for chronic subjective tinnitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous electrical nerve stimulation (TENS) on chronic subjective tinnitus. Tutar, B., Atar, S., Berkiten, G., et al.[2020]

In a pilot study involving 46 patients with acute tinnitus, those receiving verum TENS showed significant symptom relief after 4 weeks, as indicated by improvements in the Tinnitus Severity Scale, Tinnitus Questionnaire, and Tinnitus Handicap Inventory.

The study found no adverse events related to TENS treatment, suggesting it is a safe option for managing acute tinnitus symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Randomized Controlled Trial of Transcutaneous Electrical Nerve Stimulation for Patients With Acute Tinnitus. Li, L., Shi, H., Wang, M.[2021]

Transauricular vagus nerve stimulation (taVNS) at specific auricular acupoints (CO10-12, TF4) effectively activates brain regions associated with auditory processing and emotional regulation, as shown by significant changes in blood oxygenation level dependent (BOLD) signals in a study of 24 healthy subjects.

The study suggests that taVNS could be a promising treatment for tinnitus, as it demonstrated the ability to stimulate key areas of the brain involved in hearing and emotional response, indicating its potential therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI. Peng, L., Mu, K., Liu, A., et al.[2022]

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]

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Our findings demonstrate tAN is both safe and feasible in patients admitted to the inpatient psychiatric unit. tAN may be a successful adjunct ...