Auricular StimulationNCT05487664
RM1 Project 2 - tAN fMRI
A study testing Transcutaneous Auricular Neruostimulation (tAN) in people with Auricular Stimulation, run by Medical University of South Carolina at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Auricular Stimulation
- What is being tested?
- Transcutaneous Auricular Neruostimulation (tAN)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2023to 1 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-65
- Have the capacity and ability to provide one's own consent and sign the informed consent document
Who cannot join
- 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).
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- 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.
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Medical University of South Carolina Institute of Psychiatry
Charleston, South Carolina, 29425
Bashar W Badran, PhD, 843-792-6076, badran@musc.edu
About this study
Official title: Determining the Independent and Synergistic Effects of Transcutaneous Auricular Neurostimulation (tAN) on Direct Brain Activation in Healthy Individuals
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).
Read the detailed description
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.
- Conditions
- Auricular Stimulation
- Being tested
- Transcutaneous Auricular Neruostimulation (tAN)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Auricular Neruostimulation (tAN)Device
The intervention we are studying is called transcutaneous auricular neurostimulation (tAN). tAN is simply electrical nerve stimulation administered at the ear which targets both the auricular branch of the vagus nerve (ABVN) and the auriculotemporal nerve (ATN, a branch of the trigeminal nerve).
| Study group | Role | What they receive |
|---|---|---|
| Auricular Neurostimulation (Active 1) | Active comparator | •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) Receives: Device: Transcutaneous Auricular Neruostimulation (tAN) |
| Auricular Neurostimulation (Active 2) | Active comparator | •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) Receives: Device: Transcutaneous Auricular Neruostimulation (tAN) |
| Auricular Neurostimulation (Active 3) | Active comparator | •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) Receives: Device: Transcutaneous Auricular Neruostimulation (tAN) |
| Auricular Neurostimulation (Sham 1) | Sham comparator | •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) Receives: Device: Transcutaneous Auricular Neruostimulation (tAN) |
| Auricular Neurostimulation (Sham 2) | Sham comparator | •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) Receives: Device: Transcutaneous Auricular Neruostimulation (tAN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD signal changes during stimulation relative to no stimulation
. tAN will will be administered to participants within the bore of the MRI scanner while we acquire high resolution functional neuroimaging. Both a general linear model and SNM approach will be used to examine BOLD signal changes during stimulation relative to rest blocks, comparing each of the four stimulation targets within- and between subjects to determine whether stimulating two cranial nerves produces a more robust neurophysiological effect than either single nerve or sham stimulation alone.
Measured: During tAN
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2022
- Study start17 Mar 2023
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Auricular StimulationStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Borckardt, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05487664
- Sponsor's protocol ID
- Pro00122682
- Status last verified
- Dec 2025
- First submitted
- 2 Aug 2022
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Independent and Synergistic Effects of Transcutaneous Auricular Neurostimulation (tAN) on Direct Brain Activation in Healthy Individuals
- ClinicalTrials.gov ID
- NCT05487664
- Acronym / sponsor ID
- Pro00122682
- Conditions
- Auricular Stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- 17 Mar 2023 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 4 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Auricular Neurostimulation (Active 1) | Active comparator | Device: Transcutaneous Auricular Neruostimulation (tAN)•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) |
| Auricular Neurostimulation (Active 2) | Active comparator | Device: Transcutaneous Auricular Neruostimulation (tAN)•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) |
| Auricular Neurostimulation (Active 3) | Active comparator | Device: Transcutaneous Auricular Neruostimulation (tAN)•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) |
| Auricular Neurostimulation (Sham 1) | Sham comparator | Device: Transcutaneous Auricular Neruostimulation (tAN)•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) |
| Auricular Neurostimulation (Sham 2) | Sham comparator | Device: Transcutaneous Auricular Neruostimulation (tAN)•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 may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18-65
- Have the capacity and ability to provide one's own consent and sign the informed consent document
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous Auricular Neruostimulation (tAN)The intervention we are studying is called transcutaneous auricular neurostimulation (tAN). tAN is simply electrical nerve stimulation administered at the ear which targets both the auricular branch of the vagus nerve (ABVN) and the auriculotemporal nerve (ATN, a branch of the trigeminal nerve). | Device | Auricular Neurostimulation (Active 1), Auricular Neurostimulation (Active 2), Auricular Neurostimulation (Active 3), Auricular Neurostimulation (Sham 1), Auricular Neurostimulation (Sham 2) |
Primary outcome
BOLD signal changes during stimulation relative to no stimulation
Time frame: During tAN
. tAN will will be administered to participants within the bore of the MRI scanner while we acquire high resolution functional neuroimaging. Both a general linear model and SNM approach will be used to examine BOLD signal changes during stimulation relative to rest blocks, comparing each of the four stimulation targets within- and between subjects to determine whether stimulating two cranial nerves produces a more robust neurophysiological effect than either single nerve or sham stimulation alone.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Auricular Neruostimulation (tAN) in people with Auricular Stimulation, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bashar Badran, PhD (843-792-6076, badran@musc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD signal changes during stimulation relative to no stimulation (time frame: During tAN). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.