Understanding the Effects of Transauricular Vagus Nerve Stimulation on Neural Networks and Autonomic Nervous System

NCT05801809 | Completed Results FDA Device

• 1 other identifier: 2022P003200
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

vagal nerve stimulation; healthy subjects; biomarkers

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Change from baseline to 60 minutes post-taVNS.

Secondary Outcomes (1)

• Heart Rate Variability (HRV)

  Post-intervention (after 60 minutes of taVNS)

Study Arms (2)

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.

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.

Device: Transauricular vagus nerve stimulation (taVNS)

Interventions

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).

Active taVNS; Sham taVNS

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent to participate in the study.
• Subject is older than 18 years.
• Subjects should be naive to the stimulation (taVNS)

You may not qualify if:

• 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)
• 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).

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Study Sites (1)

Spaulding Hospital Cambridge

Cambridge, Massachusetts, 02138, United States

Location

Results Point of Contact

• Title: Felipe Fregni, PI
• Organization: Spaulding Rehabilitation Hospital

fregni.felipe@mgh.harvard.edu

6179526158

Study Officials

• Felipe Fregni, MD, PhD, MPH

  Spaulding Rehabilitation Hospital/Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Spaulding Neuromodulation Center

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: April 6, 2023
• Study Start: April 26, 2023
• Primary Completion: September 23, 2023
• Study Completion: March 1, 2026
• Last Updated: April 24, 2026
• Results First Posted: December 10, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)