RM1 Project 2 - tAN fMRI

  • End date
    Oct 1, 2027
  • participants needed
  • sponsor
    Medical University of South Carolina
Updated on 7 April 2023
Accepts healthy volunteers


In this one-visit, randomized, double-blind, sham-controlled trial, we plan to use a novel concurrent transcutaneous auricular neurostimulation (tAN) paradigm during functional magnetic resonance imaging (fMRI) paradigm in 96 individuals to determine whether tAN administered to two cranial nerves simultaneously produces greater neurophysiologic effects than stimulating solely to the auricular branch of the vagus nerve (ABVN) or the auriculotemporal nerve (ATN; branch of trigeminal nerve) alone. Within the MRI scanner, each participant will be connected to a series of electrodes that stimulate 4 targets (ABVN only, ATN only, ABVN plus ATN, and Sham).


The demand for chronic pain treatment has demonstrated an unprecedented increase over the last several decades, in part contributing to an unsustainable surge in opioid prescriptions. Countless patients were escalated to prolonged, high-dose opioid regimens over years of treatment. By 2014, 5.4% of US adults were estimated to use prescription opioids on a long-term basis. As the harms of opioid proliferation became increasingly clear, a dramatic paradigm shift occurred in which these drugs came to be seen as often more dangerous than beneficial for chronic pain. New clinical guidelines highlighted the risks of high-dose regimens as well as limited benefits, particularly insufficient analgesia, associated with long-term use. According to this new perspective, the preferred therapeutic modality for many patients is to significantly reduce, or even completely stop, using opioids.

Stimulation of the ABVN has demonstrated additional benefits for reducing the need for opioids for pain as well as lessening opioid withdrawal symptoms. Clinical trials of ABVN stimulation as an adjunctive treatment for pain have noted decreased intake of tramadol , remifentanil, morphine, as well as naproxen plus tramadol. A pioneering study of electrical stimulation at the cymba conchae in eight persons with opioid use disorder found significantly reduced withdrawal symptoms: first, decreases in anxiety, craving for opioids, chills, nausea; second, reduced bone and joint pain. Results in follow-up clinical trials bolstered the efficacy of ABVN stimulation for opioid withdrawal . More recently, an open-label trial of simultaneous ABVN and trigeminal stimulation found reduced withdrawal symptoms and decreased need for morphine maintenance in newborns with neonatal opioid withdrawal syndrome . This method of simultaneous vagal and trigeminal stimulation via the external ear is known as transcutaneous auricular neurostimulation (tAN), as the targets of electrical stimulation include the ABVN and auriculotemporal nerve (ATN), which is a branch of the mandibular division of the trigeminal nerve. Electrodes applied to select dermatome regions can target ear neural structures and deliver non-invasive vagus nerve stimulation (VNS) and trigeminal nerve stimulation (TNS). See Figure 1.

Use of tAN devices for pain relief is an attractive alternative to pharmacologic and opioid-based approaches because it is safe and effective and presents no addiction liability. In order to increase clinical adoption and optimize efficacy of these devices, the mechanism of action must be fully characterized.

This study is investigating the mechanism behind tAN in a healthy cohort. Using tAN combined with advanced neuroimaging, we hope to begin to understand what parts of the brain are activated during tAN, compared to sham.

Condition Auricular Stimulation
Treatment Transcutaneous Auricular Neruostimulation (tAN)
Clinical Study IdentifierNCT05487664
SponsorMedical University of South Carolina
Last Modified on7 April 2023


Yes No Not Sure

Inclusion Criteria

Age 18-65
Have the capacity and ability to provide one's own consent and sign the informed consent document

Exclusion Criteria

Contraindicated for MRI
Any current or recent untreated medical, neurological, or psychiatric conditions
Metal implant devices in the head, heart or neck
History of brain surgery
History of myocardial infarction or arrhythmia, bradycardia
Personal or family history of seizure or epilepsy or personal use of medications that substantially reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium)
Personal history of head injury, concussion, or self-report of moderate to severe traumatic brain injury
Individuals suffering from frequent/severe headaches
Individuals with a reported history of psychosis or mania, or individuals who are actively manic or psychotic
Moderate to severe alcohol or substance use disorder
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note