Acute PainNCT07827690
Effects of Transcutaneous Vagus Nerve Stimulation on Pain and Brain Activity in Healthy Adults
A study testing Active transcutaneous vagus nerve stimulation and Cold pressor test in people with Acute Pain and Pain Perception, run by David A. Purger at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn whether stimulating a nerve in the neck changes how much pain people feel. It also looks at whether this stimulation changes brain activity. The study is being done in healthy adults ages 18 to 70. The nerve being studied is called the vagus nerve. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Pain, Pain Perception, Healthy Adult Participants
- What is being tested?
- Active transcutaneous vagus nerve stimulation and Cold pressor test
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2026to Jan 2028
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults aged 18 to 70 years
- Healthy, defined as having no history of chronic medical, neurological, or psychiatric conditions
- Not currently experiencing acute illness or chronic pain
- Not currently taking medications that influence the nervous system or pain sensitivity
- Willing and able to provide written informed consent in English
Who cannot join
- History of vagal or vasovagal symptoms
- Respiratory distress
- Cardiac arrhythmia
- Sleep apnea
- Pregnancy
- Substance abuse
Show all 9Show fewer
- Primary psychiatric disorder
- Prior vagus nerve stimulation or any implanted medical device
- Significant acute or chronic neurologic illness that, in the judgment of the Principal Investigator, could compromise participant safety, limit the ability to complete the study, or compromise the objectives of the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Marissa Lowe contact
United States1 site
IU Health Neuroscience Center
Indianapolis, Indiana, 46202
Department of Neurological Surgery, 317-963-1300, dpurger@iu.edu
About this study
Official title: The Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on Acute Pain Perception and Brain Activity in Healthy Adults
The goal of this clinical trial is to learn whether stimulating a nerve in the neck changes how much pain people feel. It also looks at whether this stimulation changes brain activity. The study is being done in healthy adults ages 18 to 70.
The nerve being studied is called the vagus nerve. It runs through the neck and connects to parts of the brain that handle pain. In this study, the nerve is stimulated from outside the body using a small device placed on the skin. There is no surgery, and nothing is implanted.
Read more
The main questions it aims to answer are: (1) Does stimulating the vagus nerve lower the pain people feel during a cold water test? (2) Does stimulating the vagus nerve change the electrical activity in the brain?
Researchers will compare pain ratings and brain activity under three conditions in the same person: no stimulation, real stimulation over the vagus nerve, and sham stimulation placed nearby on the neck. Sham stimulation feels similar but is not aimed at the nerve.
Participants will: (1) Come to one visit that lasts about 90 minutes, with no follow-up visits, (2) Wear a cap that records the brain's natural electrical signals for the whole visit, (3) Place both hands in cold water, about 39 degrees Fahrenheit, up to three times for up to 2 minutes each time, (4) Rate their pain after each cold water test, (5) Wear a stimulation device on the neck during two of the three cold water tests, (6) Not be told which of those two is the real stimulation until the visit is over.
- Conditions
- Acute Pain, Pain Perception, Healthy Adult Participants
- Being tested
- Active transcutaneous vagus nerve stimulation, Sham transcutaneous vagus nerve stimulation, Cold pressor test
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active transcutaneous vagus nerve stimulationDevice
Stimulation applied over the cervical branch of the vagus nerve, anterior to the sternocleidomastoid along the carotid sheath. Pulse width 200 microseconds, frequency 30 Hz, rectangular monophasic waveform, intensity titrated between 17.8 and 39.5 volts to a mild tingling sensation below the threshold of discomfort. Stimulation is maintained for 20 minutes before the cold pressor test and continues throughout it.
Sham transcutaneous vagus nerve stimulationDevice
Identical device, parameters, and duration as the active condition, differing only in placement. The device is positioned slightly posterior on the neck, away from the cervical branch of the vagus nerve.
Cold pressor testOther
Immersion of both hands up to the wrist in water maintained at 4 degrees Celsius with ice for up to two minutes or as long as tolerated. Performed three times per participant: once with no stimulation, once during active stimulation, and once during sham stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Active Stimulation First, Then Sham | Experimental | Participants complete a cold pressor test with no stimulation, then a second cold pressor test during active transcutaneous vagus nerve stimulation, then a third during sham stimulation. Receives: Device: Active transcutaneous vagus nerve stimulation; Device: Sham transcutaneous vagus nerve stimulation; Other: Cold pressor test |
| Sham Stimulation First, Then Active | Experimental | Participants complete a cold pressor test with no stimulation, then a second cold pressor test during sham stimulation, then a third during active transcutaneous vagus nerve stimulation. Receives: Device: Active transcutaneous vagus nerve stimulation; Device: Sham transcutaneous vagus nerve stimulation; Other: Cold pressor test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity measured by the Numerical Pain Rating Scale
Participant-reported pain intensity on an 11-point scale from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Higher scores indicate greater pain. Rated immediately after each cold pressor test.
Measured: Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Pain intensity measured by the Visual Analogue Scale
Participant-reported pain intensity is marked on a 100 mm line anchored at 0 mm for no pain and 100 mm for the worst imaginable pain. The distance in millimeters from the left anchor is recorded as the score. Higher scores indicate greater pain. Rated immediately after each cold pressor test.
Measured: Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Pain threshold during cold pressor test
Time in seconds from hand immersion to the participant's first verbalized sensation of pain, recorded separately for each hand.
Measured: During each of the three cold pressor tests within a single visit, approximately 90 minutes.
Secondary outcomes (2)
Change in EEG spectral power
Change in spectral power within canonical frequency bands (delta 1 to 4 Hz, theta 4 to 8 Hz, alpha 8 to 12 Hz, beta 13 to 30 Hz, gamma above 30 Hz), measured by continuous 16-channel electroencephalography, compared across resting baseline, stimulation without noxious stimulus, and stimulation during cold pressor test.
Measured: Continuously throughout a single visit, approximately 90 minutes.
Change in EEG functional connectivity
Change in functional connectivity between brain regions, derived from continuous 16-channel electroencephalography. Phase locking values are computed for each pair of EEG channels within canonical frequency bands, and connectivity metrics are derived from those values. Coherence is assessed in the frequency domain. Analyses are restricted to predefined, theory-driven regions and frequency bands. Compared across resting baseline, stimulation without noxious stimulus, and stimulation during the cold pressor test.
Measured: Continuously throughout a single visit, approximately 90 minutes.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute PainStudies 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
- Model description
- Each participant completes three cold pressor tests in a single session. The first is always performed with no stimulation and serves as a within-subject control. Participants are then randomized to receive either active or sham stimulation first, followed by the alternate condition. Randomization uses a computer-generated allocation sequence producing two equal groups. Participants are blinded to which condition is active. Study personnel are not blinded, because condition assignment determines device placement.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David A. Purger
- Sponsor type
- University, hospital or other
- Collaborators
- Indiana University Health, Indiana University Health Methodist Hospital, Purdue University
- Responsible party
- Sponsor-investigator, David A. Purger, Indiana University
- Investigators
- David A Purger, MD, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07827690
- Sponsor's protocol ID
- 27960
- Other IDs
- SNEU-IIR-TVNS-ADULTS
- Status last verified
- Sep 2026
- First submitted
- 14 Sep 2026
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: This is a small exploratory pilot study in healthy volunteers, designed to generate preliminary effect size estimates rather than definitive findings. With a target enrollment of 20 participants at a single site, the dataset is small enough that a decision about sharing individual participant data has been deferred. The current informed consent form does not specifically address sharing de-identified individual participant data with researchers outside the study team. Any future data sharing would require review of participant consent and approval by the Indiana University Institutional Review Board. The study team will revisit this decision before study completion.
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on Acute Pain Perception and Brain Activity in Healthy Adults
- ClinicalTrials.gov ID
- NCT07827690
- Acronym / sponsor ID
- 27960
- Conditions
- Acute Pain, Pain Perception, Healthy Adult Participants
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- David A. PurgerUniversity, hospital or other
- Collaborators
- Indiana University Health, Indiana University Health Methodist Hospital, Purdue University
- Study start
- Sep 2026 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 18 Sep 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.
The goal of this clinical trial is to learn whether stimulating a nerve in the neck changes how much pain people feel. It also looks at whether this stimulation changes brain activity. The study is being done in healthy adults ages 18 to 70.
The nerve being studied is called the vagus nerve. It runs through the neck and connects to parts of the brain that handle pain. In this study, the nerve is stimulated from outside the body using a small device placed on the skin. There is no surgery, and nothing is implanted.
The main questions it aims to answer are: (1) Does stimulating the vagus nerve lower the pain people feel during a cold water test? (2) Does stimulating the vagus nerve change the electrical activity in the brain?
Researchers will compare pain ratings and brain activity under three conditions in the same person: no stimulation, real stimulation over the vagus nerve, and sham stimulation placed nearby on the neck. Sham stimulation feels similar but is not aimed at the nerve.
Participants will: (1) Come to one visit that lasts about 90 minutes, with no follow-up visits, (2) Wear a cap that records the brain's natural electrical signals for the whole visit, (3) Place both hands in cold water, about 39 degrees Fahrenheit, up to three times for up to 2 minutes each time, (4) Rate their pain after each cold water test, (5) Wear a stimulation device on the neck during two of the three cold water tests, (6) Not be told which of those two is the real stimulation until the visit is over.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Each participant completes three cold pressor tests in a single session. The first is always performed with no stimulation and serves as a within-subject control. Participants are then randomized to receive either active or sham stimulation first, followed by the alternate condition. Randomization uses a computer-generated allocation sequence producing two equal groups. Participants are blinded to which condition is active. Study personnel are not blinded, because condition assignment determines device placement.
| Arm | Type | Receives |
|---|---|---|
| Active Stimulation First, Then Sham | Experimental | Device: Active transcutaneous vagus nerve stimulation, Device: Sham transcutaneous vagus nerve stimulation, Other: Cold pressor testParticipants complete a cold pressor test with no stimulation, then a second cold pressor test during active transcutaneous vagus nerve stimulation, then a third during sham stimulation. |
| Sham Stimulation First, Then Active | Experimental | Device: Active transcutaneous vagus nerve stimulation, Device: Sham transcutaneous vagus nerve stimulation, Other: Cold pressor testParticipants complete a cold pressor test with no stimulation, then a second cold pressor test during sham stimulation, then a third during active transcutaneous vagus nerve stimulation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18 to 70 years
- Healthy, defined as having no history of chronic medical, neurological, or psychiatric conditions
- Not currently experiencing acute illness or chronic pain
- Not currently taking medications that influence the nervous system or pain sensitivity
- Willing and able to provide written informed consent in English
Key exclusion criteria (9 listed)
- History of vagal or vasovagal symptoms
- Respiratory distress
- Cardiac arrhythmia
- Sleep apnea
- Pregnancy
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 |
|---|---|---|
| Active transcutaneous vagus nerve stimulationStimulation applied over the cervical branch of the vagus nerve, anterior to the sternocleidomastoid along the carotid sheath. Pulse width 200 microseconds, frequency 30 Hz, rectangular monophasic waveform, intensity titrated between 17.8 and 39.5 volts to a mild tingling sensation below the threshold of discomfort. Stimulation is maintained for 20 minutes before the cold pressor test and continues throughout it. | Device | Active Stimulation First, Then Sham, Sham Stimulation First, Then Active |
| Sham transcutaneous vagus nerve stimulationIdentical device, parameters, and duration as the active condition, differing only in placement. The device is positioned slightly posterior on the neck, away from the cervical branch of the vagus nerve. | Device | Active Stimulation First, Then Sham, Sham Stimulation First, Then Active |
| Cold pressor testImmersion of both hands up to the wrist in water maintained at 4 degrees Celsius with ice for up to two minutes or as long as tolerated. Performed three times per participant: once with no stimulation, once during active stimulation, and once during sham stimulation. | Other | Active Stimulation First, Then Sham, Sham Stimulation First, Then Active |
Primary outcome
Pain intensity measured by the Numerical Pain Rating Scale
Time frame: Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Participant-reported pain intensity on an 11-point scale from 0 to 10, where 0 is no pain and 10 is the worst pain imaginable. Higher scores indicate greater pain. Rated immediately after each cold pressor test.
Pain intensity measured by the Visual Analogue Scale
Time frame: Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.
Participant-reported pain intensity is marked on a 100 mm line anchored at 0 mm for no pain and 100 mm for the worst imaginable pain. The distance in millimeters from the left anchor is recorded as the score. Higher scores indicate greater pain. Rated immediately after each cold pressor test.
Pain threshold during cold pressor test
Time frame: During each of the three cold pressor tests within a single visit, approximately 90 minutes.
Time in seconds from hand immersion to the participant's first verbalized sensation of pain, recorded separately for each hand.
2 secondary outcomes
Change in EEG spectral power
Time frame: Continuously throughout a single visit, approximately 90 minutes.
Change in EEG functional connectivity
Time frame: Continuously throughout a single visit, approximately 90 minutes.
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 Sep 2026.
- Individual participant dataSharing planned: No. This is a small exploratory pilot study in healthy volunteers, designed to generate preliminary effect size estimates rather than definitive findings. With a target enrollment of 20 participants at a single site, the dataset is small enough that a decision about sharing individual participant data has been deferred. The current informed consent form does not specifically address sharing de-identified individual participant data with researchers outside the study team. Any future data sharing would require review of participant consent and approval by the Indiana University Institutional Review Board. The study team will revisit this decision before study completion.
Related trials for Acute Pain
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruitingPhase 2
A Clinical Trial of MK-6916 in Participants With Pain After Bunion Removal Surgery (MK-6916-007)
Pain Management
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
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.
Marissa Lowe contact
David A Purger, MD, PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active transcutaneous vagus nerve stimulation and Cold pressor test in people with Acute Pain and Pain Perception, run by David A. Purger 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 5 inclusion and 9 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: opening soon, as of the sponsor's last update on 18 Sep 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. 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 Caliel Hines (317-963-7010, calhines@iu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain intensity measured by the Numerical Pain Rating Scale (time frame: Immediately after each of the three cold pressor tests during a single visit, approximately 90 minutes.). The study lists 3 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 18 Sep 2026.