Impact of Transcutaneous Vagal Nerve Stimulation on Stress Response in Major Depression

NCT04448327 | Completed FDA Device

• 2 other identifiers: 2020P0012121U54MH118919-01A1
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This study will identify the sex-dependent impact of expiratory-gated transcutaneous vagus nerve stimulation (tVNS) on the modulation of the stress response circuitry and associated physiology in major depressive disorder (MDD). We will evaluate a sample of 80 adults with recurrent MDD randomized to receive active or sham expiratory-gated tVNS during a functional magnetic resonance imaging (fMRI) session, with simultaneous mood and physiological assessments. We hypothesize that expiratory-gated tVNS will effectively modulate, in a sex-dependent manner, specific brainstem-cortical pathways of the stress circuitry and attenuate physiological deficits in MDD.

Conditions

Major Depressive Disorder

Keywords

Autonomic Nervous System; Transcutaneous Vagus Nerve Stimulation; Stress Response Circuitry; Functional Magnetic Resonance Imaging; Sex Differences

Outcome Measures

Primary Outcomes (2)

• Brain activity during functional magnetic resonance imaging (fMRI)

  Changes in fMRI BOLD signal (percent BOLD signal change) of the stress response circuitry between active and sham tVNS.

  1 hour

• Cardiac autonomic function during functional magnetic resonance imaging (fMRI)

  Changes in cardiac autonomic function (High Frequency power-Heart Rate Variability) between active and sham tVNS.

  1 hour

Secondary Outcomes (3)

• Change in serum cortisol levels

  2 hours

• Change in serum levels of pro-inflammatory cytokines

  2 hours

• Change in depressive symptoms assessed by the Beck Depression Inventory

  2 hours

Study Arms (2)

Active tVNS

EXPERIMENTAL

Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle

Device: active tVNS

Sham tVNS

SHAM COMPARATOR

Sham transcutaneous vagus nerve stimulation on the left auricle

Device: Sham tVNS

Interventions

active tVNS DEVICE

non-painful electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session

Also known as: transcutaneous vagus nerve stimulation

Active tVNS

Sham tVNS DEVICE

Sham stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session

Also known as: transcutaneous vagus nerve stimulation

Sham tVNS

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current or past diagnosis of recurrent Major Depressive Disorder

You may not qualify if:

• History of neuroleptic use
• Any psychiatric disorder involving a history of psychosis (e.g. schizophrenia, bipolar I disorder)
• Active suicidal ideation with intent and/or plan or history of a suicide attempt within the last year
• Moderate or severe substance use disorder within the past 12 months
• Diagnosis of significant cardiovascular or cerebrovascular disease (e.g. congestive heart failure, stroke, cardiac conduction disorders, history of asystole or non-sustained ventricular tachycardia)
• Diseases affecting the CNS (e.g. MS, epilepsy, neurodegenerative diseases, etc.)
• Traumatic brain injury with cognitive sequelae
• MRI or tVNS contraindications (e.g. claustrophobia, metallic implants or devices)
• Pregnancy (uncommon, given the age of this cohort is 50+ years) due to unknown health risks for the fetus

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Ronald G Garcia, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 25, 2020
• Study Start: January 29, 2021
• Primary Completion: June 13, 2025
• Study Completion: June 14, 2025
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)