Healthy VolunteersNCT05801809
Understanding the Effects of Transauricular Vagus Nerve Stimulation on Neural Networks and Autonomic Nervous System
A study testing Transauricular vagus nerve stimulation (taVNS) in people with Healthy Volunteers, run by Spaulding Rehabilitation Hospital at 1 site in United States.
Trial summary
This trial aims to perform an exploratory, mechanistic, randomized double-blind sham-control trial in healthy participants to assess the physiologic effects of a single 60 minutes session of bilateral taVNS, on neural networks and autonomic function. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Transauricular vagus nerve stimulation (taVNS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Apr 2023to 1 Mar 2026
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Able to provide informed consent to participate in the study.
- Subject is older than 18 years.
- Subjects should be naive to the stimulation (taVNS)
Who cannot join
- Pregnancy.
- Subjects who have had a neuropsychiatric or a cardiac disorder diagnosis and have received treatment and chronic medication in the past six months, or who have functional deficits as a result.
- History of alcohol or drug abuse within the past 6 months as self-reported.
- Presence of the following contraindication to transauricular vagus nerve stimulation
- Ferromagnetic metal in the head and in the cranium (e.g., plates or pins, bullets, shrapnel)
- Implanted cranial electronic medical devices (e.g., cochlear implants)
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- Implanted cardiac devices (e.g., pacemaker)
- Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure, or chronic obstructive pulmonary disease).
- Uncontrolled epilepsy, as defined by previous clinical seizures in the past 3 months in patients with treatment for epilepsy.
- Suffering from severe depression (as defined by a score of >30 in the Beck Depression Inventory).
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Hospital Cambridge
Cambridge, Massachusetts, 02138
About this study
Official title: Understanding the Effects of Non-invasive Transauricular Vagus Nerve Stimulation (taVNS) on Neural Networks and Autonomic Nervous System: a Randomized Double-blind Sham-control Mechanistic Trial in Healthy Participants
This trial aims to perform an exploratory, mechanistic, randomized double-blind sham-control trial in healthy participants to assess the physiologic effects of a single 60 minutes session of bilateral taVNS, on neural networks and autonomic function.
Read the detailed description
Several studies have shown promising results of taVNS to treat various disorders such as depression, anxiety, Alzheimer's disease, headache, obesity, and diabetes. However, no mechanistic studies have investigated the taVNS neural network and autonomic nervous system effects of this technique. Therefore, we aim to assess how taVNS can affect EEG metrics and HRV and assess its safety. Also, we aim to evaluate predictors that can influence the response to taVNS, so understanding the variables associated with response to taVNS can help the design of future clinical trials to maximize the effects of this intervention.
- Conditions
- Healthy Volunteers
- Being tested
- Transauricular vagus nerve stimulation (taVNS)
- Keywords
- vagal nerve stimulation, healthy subjects, biomarkers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transauricular vagus nerve stimulation (taVNS)Device
Transauricular vagus nerve stimulation (taVNS) is a simple technique in which small surface electrodes are placed over the skin of the ear that are thought to be innervated by the auricular branch of the vagus nerve (ABVN).
| Study group | Role | What they receive |
|---|---|---|
| Active taVNS | Experimental | TaVNS will be administered by an earset, with conductive eartips placed on the auricular concha of the ears, connected to a stimulator, and during active stimulation, we stimulate both the cymba conchae and external auditory canal of both left and right ears with the following parameters: 30Hz, 200-250 us, and with adjustable intensity for 60 min. Receives: Device: Transauricular vagus nerve stimulation (taVNS) |
| Sham taVNS | Sham comparator | Sham condition will have the same device, with an earset, and conductive eartips placed in the same location of the active stimulation; however during 60 min there will be no current and the device will be turned off. Receives: Device: Transauricular vagus nerve stimulation (taVNS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting-state Electroencephalogram (EEG)
Resting-state EEG was recorded using a 64-channel high-density EGI system (Electrical Geodesics, Inc., Eugene, USA) under the eyes closed condition. Data was filtered into standard frequency bands using short-time Fourier transformation (STFT): delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-80 Hz).
Frontal asymmetry was computed as the difference in power between homologous left and right frontal electrodes (e.g., F3-F4) in the alpha band.
Measured: Change from baseline to 60 minutes post-intervention.
Conditioned Pain Modulation (CPM) Response - Change in Pain Ratings on the Pain-6 Scale (0-10)
Pain intensity was measured using the Numeric Pain Scale (NPS; 0 = no pain, 10 = worst pain). Higher scores indicate worse pain. A "pain-6 temperature" was first identified (temperature that elicits NPS = 6).
Test stimulus: Pain-6 temperature applied for 30s; participants rated pain at 10, 20, and 30s. The test-stimulus score is the average of the three NPS ratings.
Conditioned stimulus: After 5 minutes, the left hand was immersed in 10-12°C water for 30s while the same pain-6 temperature was applied again. Pain was rated the same way, and the conditioned-stimulus score is the average of the three NPS ratings.
CPM calculation = (test-stimulus average) - (conditioned-stimulus average). Positive values = better endogenous pain inhibition; negative values = worse.
Measured: Change from baseline to 60 minutes post-taVNS.
Secondary outcomes (1)
Heart Rate Variability (HRV)
HRV from ECG on non-dominant hand. High-frequency HRV calculated from 5-min resting recordings; higher values indicate greater parasympathetic activity. Post-stimulation values (60 min) were analyzed.
Measured: Post-intervention (after 60 minutes of taVNS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2023
- Study start26 Apr 2023
- Primary completion23 Sep 2023
- Study completion1 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spaulding Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital
- Investigators
- Felipe Fregni, MD, PhD, MPH, Principal investigator, Spaulding Rehabilitation Hospital/Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05801809
- Sponsor's protocol ID
- 2022P003200
- Status last verified
- Apr 2026
- First submitted
- 27 Feb 2023
- Last updated
- 24 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Effects of Non-invasive Transauricular Vagus Nerve Stimulation (taVNS) on Neural Networks and Autonomic Nervous System: a Randomized Double-blind Sham-control Mechanistic Trial in Healthy Participants
- ClinicalTrials.gov ID
- NCT05801809
- Acronym / sponsor ID
- 2022P003200
- Conditions
- Healthy Volunteers
- Keywords
- vagal nerve stimulation, healthy subjects, biomarkers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Spaulding Rehabilitation HospitalUniversity, hospital or other
- Study start
- 26 Apr 2023 (actual)
- Primary completion
- 23 Sep 2023 (actual)
- Study completion
- 1 Mar 2026 (actual)
- First posted
- 6 Apr 2023 (actual)
- Results
- Posted 10 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial aims to perform an exploratory, mechanistic, randomized double-blind sham-control trial in healthy participants to assess the physiologic effects of a single 60 minutes session of bilateral taVNS, on neural networks and autonomic function.
Detailed description
Several studies have shown promising results of taVNS to treat various disorders such as depression, anxiety, Alzheimer's disease, headache, obesity, and diabetes. However, no mechanistic studies have investigated the taVNS neural network and autonomic nervous system effects of this technique. Therefore, we aim to assess how taVNS can affect EEG metrics and HRV and assess its safety. Also, we aim to evaluate predictors that can influence the response to taVNS, so understanding the variables associated with response to taVNS can help the design of future clinical trials to maximize the effects of this intervention.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active taVNS | Experimental | Device: Transauricular vagus nerve stimulation (taVNS)TaVNS will be administered by an earset, with conductive eartips placed on the auricular concha of the ears, connected to a stimulator, and during active stimulation, we stimulate both the cymba conchae and external auditory canal of both left and right ears with the following parameters: 30Hz, 200-250 us, and with adjustable intensity for 60 min. |
| Sham taVNS | Sham comparator | Device: Transauricular vagus nerve stimulation (taVNS)Sham condition will have the same device, with an earset, and conductive eartips placed in the same location of the active stimulation; however during 60 min there will be no current and the device will be turned off. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Able to provide informed consent to participate in the study.
- Subject is older than 18 years.
- Subjects should be naive to the stimulation (taVNS)
Key exclusion criteria (10 listed)
- Pregnancy.
- Subjects who have had a neuropsychiatric or a cardiac disorder diagnosis and have received treatment and chronic medication in the past six months, or who have functional deficits as a result.
- History of alcohol or drug abuse within the past 6 months as self-reported.
- Presence of the following contraindication to transauricular vagus nerve stimulation
- Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure, or chronic obstructive pulmonary disease).
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 |
|---|---|---|
| Transauricular vagus nerve stimulation (taVNS)Transauricular vagus nerve stimulation (taVNS) is a simple technique in which small surface electrodes are placed over the skin of the ear that are thought to be innervated by the auricular branch of the vagus nerve (ABVN). | Device | Active taVNS, Sham taVNS |
Primary outcome
Resting-state Electroencephalogram (EEG)
Time frame: Change from baseline to 60 minutes post-intervention.
Resting-state EEG was recorded using a 64-channel high-density EGI system (Electrical Geodesics, Inc., Eugene, USA) under the eyes closed condition. Data was filtered into standard frequency bands using short-time Fourier transformation (STFT): delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-80 Hz). Frontal asymmetry was computed as the difference in power between homologous left and right frontal electrodes (e.g., F3-F4) in the alpha band.
Conditioned Pain Modulation (CPM) Response - Change in Pain Ratings on the Pain-6 Scale (0-10)
Time frame: Change from baseline to 60 minutes post-taVNS.
Pain intensity was measured using the Numeric Pain Scale (NPS; 0 = no pain, 10 = worst pain). Higher scores indicate worse pain. A "pain-6 temperature" was first identified (temperature that elicits NPS = 6). Test stimulus: Pain-6 temperature applied for 30s; participants rated pain at 10, 20, and 30s. The test-stimulus score is the average of the three NPS ratings. Conditioned stimulus: After 5 minutes, the left hand was immersed in 10-12°C water for 30s while the same pain-6 temperature was applied again. Pain was rated the same way, and the conditioned-stimulus score is the average of the three NPS ratings. CPM calculation = (test-stimulus average) - (conditioned-stimulus average). Positive values = better endogenous pain inhibition; negative values = worse.
1 secondary outcome
Heart Rate Variability (HRV)
Time frame: Post-intervention (after 60 minutes of taVNS)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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. This study is not recruiting at the moment.
Felipe Fregni, MD, PhD, MPH principal investigator
Spaulding Rehabilitation Hospital/Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transauricular vagus nerve stimulation (taVNS) in people with Healthy Volunteers, run by Spaulding Rehabilitation Hospital 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 3 inclusion and 10 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: finished, as of the sponsor's last update on 24 Apr 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 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?
Yes. Results are posted in the registry (first posted 10 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting-state Electroencephalogram (EEG) (time frame: Change from baseline to 60 minutes post-intervention.). The study lists 2 primary outcomes in all. 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 24 Apr 2026.