Healthy VolunteersNCT07662291
Frequency Effects of Transcutaneous Trigeminal Nerve Stimulation (eTNS) on Brain and Autonomic Function
A study testing 2Hz Transcutaneous Trigeminal Nerve Stimulation and 120Hz Transcutaneous Trigeminal Nerve Stimulation in people with Healthy Volunteers and fMRI Research, run by Xidian University at 1 site in China.
Trial summary
This study aims to investigate how different frequencies of transcutaneous Trigeminal Nerve Stimulation (eTNS) affect brain activity and the autonomic nervous system in healthy individuals. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, fMRI Research
- What is being tested?
- 2Hz Transcutaneous Trigeminal Nerve Stimulation and 120Hz Transcutaneous Trigeminal Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteChina
- Study dates
- 6 Aug 2026to 20 Aug 2026
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, trigeminal neuralgia, facial skin lesions, or active skin diseases on the forehead).
- Current or recent (within the past month) use of any medications known to affect the central nervous system or the autonomic nervous system (e.g., antidepressants, beta-blockers, sedatives, or sympathomimetics).
- 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 session.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xidian University
Xi'an, Shaanxi, 71000
Xue-Juan Yang, 13227038185, xjyang@xidian.edu.cn
About this study
Official title: A Randomized, Sham-Controlled, Crossover fMRI Study on the Frequency Effects of Transcutaneous Trigeminal Nerve Stimulation on Central-Autonomic Coupling in Healthy Subjects
This study aims to investigate how different frequencies of transcutaneous Trigeminal Nerve Stimulation (eTNS) affect brain activity and the autonomic nervous system in healthy individuals. Participants will undergo a 3T functional magnetic resonance imaging (fMRI) scan while receiving three different types of nerve stimulation: 2Hz eTNS, 120Hz eTNS, and a sham (inactive) stimulation. The order of these stimulations will be randomly assigned. During the brain scan, researchers will simultaneously monitor the participants' breathing and heart rhythms (using a finger sensor). The main goal is to understand how changing the frequency of eTNS influences the connection between the brain's networks and the body's unconscious physiological responses.
Read the detailed description
This is an exploratory, randomized, sham-controlled, within-subject crossover fMRI study designed to evaluate the frequency-dependent effects of transcutaneous Trigeminal Nerve Stimulation (eTNS) on central-autonomic coupling in healthy volunteers.
Participants will undergo functional neuroimaging in a 3T MRI scanner. The imaging protocol consists of a structural T1-weighted scan and three functional Blood Oxygenation Level-Dependent (BOLD) sequences corresponding to three intervention arms: 2Hz-eTNS, 120Hz-eTNS, and Sham stimulation. The order of the three stimulation conditions will be randomized for each participant. To minimize potential carryover effects, the structural T1 scan will be acquired between the two active (real) stimulation sequences.
Each functional BOLD sequence will last for 7 minutes and 30 seconds and will utilize a block design. This design consists of alternating 30-second "ON" blocks (where the stimulation is active) and 30-second "OFF" blocks (where the stimulation is inactive).
Concurrently with the fMRI acquisition, continuous physiological monitoring will be conducted. This includes recording respiratory effort and photoplethysmography (PPG) via a finger pulse oximeter to capture peripheral autonomic metrics.
The primary and secondary analyses will focus on quantifying BOLD signal responses, evaluating dynamic changes in brain functional connectivity, assessing variations in autonomic nervous system metrics (such as heart rate variability derived from the PPG), and exploring the mechanisms of central-autonomic coupling across the different stimulation frequencies.
- Conditions
- Healthy Volunteers, fMRI Research
- Being tested
- 2Hz Transcutaneous Trigeminal Nerve Stimulation, 120Hz Transcutaneous Trigeminal Nerve Stimulation, Sham Transcutaneous Trigeminal Nerve Stimulation
- Keywords
- Transcutaneous Trigeminal Nerve Stimulation, eTNS, Neuromodulation, Functional Magnetic Resonance Imaging / fMRI, Functional Connectivity, Frequency Effect, Blood Oxygenation Level-Dependent / BOLD, Central-Autonomic Coupling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2Hz Transcutaneous Trigeminal Nerve StimulationDevice
Active electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 2Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography).
120Hz Transcutaneous Trigeminal Nerve StimulationDevice
Active electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 120Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography).
Sham Transcutaneous Trigeminal Nerve StimulationDevice
An inactive or sensory-matched sham electrical stimulation designed to mimic the physical sensation of the device being active without delivering the therapeutic frequencies (2Hz or 120Hz). It is administered synchronously with the fMRI BOLD sequence and physiological monitoring to serve as a baseline comparator.
| Study group | Role | What they receive |
|---|---|---|
| 2Hz-eTNS Condition | Experimental | In this crossover phase, participants will receive 2Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. The stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, which alternates between 30-second "ON" periods (active 2Hz stimulation) and 30-second "OFF" periods (no stimulation). Receives: Device: 2Hz Transcutaneous Trigeminal Nerve Stimulation |
| 120Hz-eTNS Condition | Experimental | In this crossover phase, participants will receive 120Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. Similar to other active conditions, the stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, alternating between 30-second "ON" periods (active 120Hz stimulation) and 30-second "OFF" periods (no stimulation). Receives: Device: 120Hz Transcutaneous Trigeminal Nerve Stimulation |
| Sham-eTNS Condition | Sham comparator | In this crossover phase, participants will undergo the same fMRI scanning procedure and wear the exact same electrode pads as the active conditions, but will receive a sham stimulation. This phase also lasts for 7 minutes and 30 seconds and utilizes a simulated 30-second "ON" / 30-second "OFF" block design to maintain double-blinding. Receives: Device: Sham Transcutaneous Trigeminal Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Blood Oxygenation Level-Dependent (BOLD) Signal Amplitude in the Brainstem
The metric is the percent signal change in BOLD amplitude within predefined Regions of Interest (ROIs) of the brainstem (e.g., trigeminal nuclei, locus coeruleus, nucleus tractus solitarii). It is calculated as the BOLD signal difference between the 30-second stimulation "ON" blocks and the 30-second "OFF" blocks. Data will be aggregated as the mean percentage of BOLD signal change for each stimulation condition.
Measured: During the 7-minute and 30-second fMRI scan for each stimulation condition.
Secondary outcomes (4)
Functional Connectivity (FC) within and outside the Central Autonomic Network
The strength of dynamic and static functional connectivity between key nodes of the CAN and other whole-brain regions. Connectivity matrices will be computed and compared across the 2Hz-eTNS, 120Hz-eTNS, and Sham conditions to evaluate how different stimulation frequencies modulate brain network communications.
Measured: During the 7-minute and 30-second fMRI scan for each stimulation condition.
Change in Heart Rate Variability Assessed by Low Frequency to High Frequency (LF/HF) Ratio
The LF/HF ratio is a frequency-domain measure of heart rate variability derived from PPG data, reflecting the sympathovagal balance. Data will be aggregated as the mean LF/HF ratio during each stimulation condition.
Measured: Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
Change in Respiratory Rate
Respiratory rate is extracted from concurrent respiratory belt signals to assess respiratory patterns. Data will be aggregated as the mean respiratory rate (measured in breaths per minute) during each stimulation condition.
Measured: Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
Central-Autonomic Coupling Index
The degree of synchronization between central neural activity and peripheral autonomic output. This will be quantified by calculating the correlation coefficients or mutual information between the low-frequency fluctuations of the BOLD signals in CAN regions and the concurrent peripheral autonomic time-series data (HRV and respiration). The coupling strength will be compared between the 2Hz and 120Hz conditions.
Measured: Computed from data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2026
- Study start6 Aug 2026 (estimated)
- Primary completion20 Aug 2026 (estimated)
- Study completion20 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xidian University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07662291
- Sponsor's protocol ID
- 20260617
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2026
- Last updated
- 23 Jun 2026
- Results posted
- No
- 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 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Sham-Controlled, Crossover fMRI Study on the Frequency Effects of Transcutaneous Trigeminal Nerve Stimulation on Central-Autonomic Coupling in Healthy Subjects
- ClinicalTrials.gov ID
- NCT07662291
- Acronym / sponsor ID
- 20260617
- Conditions
- Healthy Volunteers, fMRI Research
- Keywords
- Transcutaneous Trigeminal Nerve Stimulation, eTNS, Neuromodulation, Functional Magnetic Resonance Imaging / fMRI, Functional Connectivity, Frequency Effect, Blood Oxygenation Level-Dependent / BOLD, Central-Autonomic Coupling
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Xidian UniversityUniversity, hospital or other
- Study start
- 6 Aug 2026 (estimated)
- Primary completion
- 20 Aug 2026 (estimated)
- Study completion
- 20 Aug 2026 (estimated)
- First posted
- 23 Jun 2026 (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.
This study aims to investigate how different frequencies of transcutaneous Trigeminal Nerve Stimulation (eTNS) affect brain activity and the autonomic nervous system in healthy individuals. Participants will undergo a 3T functional magnetic resonance imaging (fMRI) scan while receiving three different types of nerve stimulation: 2Hz eTNS, 120Hz eTNS, and a sham (inactive) stimulation. The order of these stimulations will be randomly assigned. During the brain scan, researchers will simultaneously monitor the participants' breathing and heart rhythms (using a finger sensor). The main goal is to understand how changing the frequency of eTNS influences the connection between the brain's networks and the body's unconscious physiological responses.
Detailed description
This is an exploratory, randomized, sham-controlled, within-subject crossover fMRI study designed to evaluate the frequency-dependent effects of transcutaneous Trigeminal Nerve Stimulation (eTNS) on central-autonomic coupling in healthy volunteers.
Participants will undergo functional neuroimaging in a 3T MRI scanner. The imaging protocol consists of a structural T1-weighted scan and three functional Blood Oxygenation Level-Dependent (BOLD) sequences corresponding to three intervention arms: 2Hz-eTNS, 120Hz-eTNS, and Sham stimulation. The order of the three stimulation conditions will be randomized for each participant. To minimize potential carryover effects, the structural T1 scan will be acquired between the two active (real) stimulation sequences.
Each functional BOLD sequence will last for 7 minutes and 30 seconds and will utilize a block design. This design consists of alternating 30-second "ON" blocks (where the stimulation is active) and 30-second "OFF" blocks (where the stimulation is inactive).
Concurrently with the fMRI acquisition, continuous physiological monitoring will be conducted. This includes recording respiratory effort and photoplethysmography (PPG) via a finger pulse oximeter to capture peripheral autonomic metrics.
The primary and secondary analyses will focus on quantifying BOLD signal responses, evaluating dynamic changes in brain functional connectivity, assessing variations in autonomic nervous system metrics (such as heart rate variability derived from the PPG), and exploring the mechanisms of central-autonomic coupling across the different stimulation frequencies.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 2Hz-eTNS Condition | Experimental | Device: 2Hz Transcutaneous Trigeminal Nerve StimulationIn this crossover phase, participants will receive 2Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. The stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, which alternates between 30-second "ON" periods (active 2Hz stimulation) and 30-second "OFF" periods (no stimulation). |
| 120Hz-eTNS Condition | Experimental | Device: 120Hz Transcutaneous Trigeminal Nerve StimulationIn this crossover phase, participants will receive 120Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. Similar to other active conditions, the stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, alternating between 30-second "ON" periods (active 120Hz stimulation) and 30-second "OFF" periods (no stimulation). |
| Sham-eTNS Condition | Sham comparator | Device: Sham Transcutaneous Trigeminal Nerve StimulationIn this crossover phase, participants will undergo the same fMRI scanning procedure and wear the exact same electrode pads as the active conditions, but will receive a sham stimulation. This phase also lasts for 7 minutes and 30 seconds and utilizes a simulated 30-second "ON" / 30-second "OFF" block design to maintain double-blinding. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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 transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, trigeminal neuralgia, facial skin lesions, or active skin diseases on the forehead).
- Current or recent (within the past month) use of any medications known to affect the central nervous system or the autonomic nervous system (e.g., antidepressants, beta-blockers, sedatives, or sympathomimetics).
- History of substance abuse, heavy smoking, or excessive daily consumption of alcohol or caffeine.
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 |
|---|---|---|
| 2Hz Transcutaneous Trigeminal Nerve StimulationActive electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 2Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography). | Device | 2Hz-eTNS Condition |
| 120Hz Transcutaneous Trigeminal Nerve StimulationActive electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 120Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography). | Device | 120Hz-eTNS Condition |
| Sham Transcutaneous Trigeminal Nerve StimulationAn inactive or sensory-matched sham electrical stimulation designed to mimic the physical sensation of the device being active without delivering the therapeutic frequencies (2Hz or 120Hz). It is administered synchronously with the fMRI BOLD sequence and physiological monitoring to serve as a baseline comparator. | Device | Sham-eTNS Condition |
Primary outcome
Difference in Blood Oxygenation Level-Dependent (BOLD) Signal Amplitude in the Brainstem
Time frame: During the 7-minute and 30-second fMRI scan for each stimulation condition.
The metric is the percent signal change in BOLD amplitude within predefined Regions of Interest (ROIs) of the brainstem (e.g., trigeminal nuclei, locus coeruleus, nucleus tractus solitarii). It is calculated as the BOLD signal difference between the 30-second stimulation "ON" blocks and the 30-second "OFF" blocks. Data will be aggregated as the mean percentage of BOLD signal change for each stimulation condition.
4 secondary outcomes
Functional Connectivity (FC) within and outside the Central Autonomic Network
Time frame: During the 7-minute and 30-second fMRI scan for each stimulation condition.
Change in Heart Rate Variability Assessed by Low Frequency to High Frequency (LF/HF) Ratio
Time frame: Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
Change in Respiratory Rate
Time frame: Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
Central-Autonomic Coupling Index
Time frame: Computed from data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
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 23 Jun 2026.
- Individual participant dataSharing planned: No
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Screening Protocol
Pain
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 2Hz Transcutaneous Trigeminal Nerve Stimulation and 120Hz Transcutaneous Trigeminal Nerve Stimulation in people with Healthy Volunteers and fMRI Research, run by Xidian University at 1 site in China.
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 5 inclusion and 6 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 23 Jun 2026. 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 China. 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 Xue-Juan Yang (13227038185, xjyang@xidian.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Blood Oxygenation Level-Dependent (BOLD) Signal Amplitude in the Brainstem (time frame: During the 7-minute and 30-second fMRI scan for each stimulation condition.). 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 23 Jun 2026.