Effects of Transcutaneous Vagus Nerve Stimulation on Pain and Brain Activity in Healthy Adults

NCT07827690 | Not Yet Recruiting FDA Device

• 2 other identifiers: 27960SNEU-IIR-TVNS-ADULTS
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pain Perception; Acute Pain; Healthy Adult Participants

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  During each of the three cold pressor tests within a single visit, approximately 90 minutes.

Secondary Outcomes (2)

• Change in EEG spectral power

  Continuously throughout a single visit, approximately 90 minutes.

• Change in EEG functional connectivity

  Continuously throughout a single visit, approximately 90 minutes.

Study Arms (2)

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.

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.

Device: Active transcutaneous vagus nerve stimulation; Device: Sham transcutaneous vagus nerve stimulation; Other: Cold pressor test

Interventions

Active transcutaneous vagus nerve stimulation DEVICE

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.

Active Stimulation First, Then Sham; Sham Stimulation First, Then Active

Sham transcutaneous vagus nerve stimulation DEVICE

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.

Active Stimulation First, Then Sham; Sham Stimulation First, Then Active

Cold pressor test OTHER

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.

Active Stimulation First, Then Sham; Sham Stimulation First, Then Active

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of vagal or vasovagal symptoms
• Respiratory distress
• Cardiac arrhythmia
• Sleep apnea
• Pregnancy
• Substance abuse
• 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

Sponsors & Collaborators

• David A. Purger: lead
• Indiana University Health: collaborator
• Purdue University: collaborator
• Indiana University Health Methodist Hospital: collaborator

Study Sites (1)

IU Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• David A Purger, MD, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caliel Hines

CONTACT

317-963-7010; calhines@iu.edu

Marissa Lowe

CONTACT

lowemj@iu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurological Surgery, Adjunct Assistant Professor of Psychiatry Indiana University School of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 18, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)