Investigating the Transcutaneous vs. Transcranial Mechanisms of Trigeminal Nerve Stimulation (eTN… (NCT07657260) | Clinical Trial Compass
RecruitingNot Applicable
Investigating the Transcutaneous vs. Transcranial Mechanisms of Trigeminal Nerve Stimulation (eTNS) Using fMRI
China25 participantsStarted 2026-06-21
Plain-language summary
Transcutaneous Trigeminal Nerve Stimulation (eTNS) is a non-invasive technique that modulates brain activity by applying electrical currents to the forehead. However, it remains unclear whether its effects are primarily driven by activating peripheral nerves in the skin (the transcutaneous pathway) or by the electrical current passing directly through the skull into the brain (the transcranial pathway).
This study aims to differentiate these two mechanisms in healthy volunteers. Participants will complete two separate MRI scanning sessions. In one session, a local anesthetic (lidocaine) will be applied to numb the skin over the forehead (specifically the supraorbital nerve branch) to temporarily block the peripheral nerve signals. In the other session, no anesthesia will be used. During both sessions, participants will receive active direct current eTNS (DC-eTNS) and a sham (inactive) stimulation while inside a 3T MRI scanner.
Researchers will simultaneously measure brain activity (fMRI) and physiological signals (breathing and heart rate). By comparing the brain and bodily responses between the anesthetized and non-anesthetized conditions, the study seeks to determine exactly how eTNS signals travel to and affect the brainstem, cortex, and autonomic nervous system.
Who can participate
Age range
18 Years – 35 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Healthy volunteers, aged 18 to 40 years old.
. Right-handed.
. Generally healthy with no history of neurological, psychiatric, or severe cardiovascular diseases.
. Normal physical and neurological examinations.
. Capable of understanding the study procedures and voluntarily signing the written informed consent form.
Exclusion criteria
. Known allergy, hypersensitivity, or adverse reactions to Lidocaine or other amide-type local anesthetics. (Crucial for this specific study design)
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This study involves stimulating the trigeminal nerve either through the skin or directly through the skull while inside an MRI scanner — what should I know about how those two stimulation methods feel physically, and are there any discomfort or safety concerns I should discuss before agreeing to participate?
2Since this trial is enrolling healthy volunteers and is measuring brain activity patterns in the brainstem using fMRI, does my own health history — for example, any neurological conditions, metal implants, or medications — affect whether participating would be appropriate for me?
3The study is measuring something called Amplitude of Low-Frequency Fluctuations in the brainstem, which sounds quite technical — can you help me understand what researchers are hoping to learn from that measurement, and how this basic science research might eventually connect to treatments for real conditions?
4Since this is listed as Phase NA, which typically means it's a non-drug mechanistic or device study rather than a treatment trial, what does that mean in terms of what's already known about the safety of this type of nerve stimulation, and what unknowns still exist?
5What does participation actually involve in terms of time, number of visits, and what happens inside the MRI scanner, and are there any people who should be especially cautious about this kind of study based on their personal circumstances?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Amplitude of Low-Frequency Fluctuations (ALFF) in the Brainstem
Timeframe: Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
. Contraindications to MRI scanning (e.g., claustrophobia, cardiac pacemakers, artificial cochlea, metallic braces, or any other ferromagnetic implants).
. Female participants who are pregnant, lactating, or suspect they might be pregnant.
. Contraindications to transcranial or transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, implanted brain stimulators).
. Any active skin disease, inflammation, lesions, cuts, or abrasions on the forehead (specifically over the supraorbital area), which could alter electrical impedance or anesthetic absorption.
. History of trigeminal neuralgia, facial nerve palsy, or chronic facial pain. Current or recent (within the past month) use of any medications known to affect the central nervous system, autonomic nervous system, or pain perception (e.g., analgesics, antidepressants, beta-blockers, or sedatives).
. History of substance abuse, heavy smoking, or excessive daily consumption of alcohol or caffeine.
. Irregular sleep patterns, shift work, or severe sleep deprivation within 24 hours prior to the scanning sessions.