Effects of non-invasive vagus nerve stimulation on stress response in depression

Sex-Dependent Impact of Transcutaneous Vagal Nerve Stimulation on the Stress Response Circuitry and Autonomic Dysregulation in Major Depression

Not applicable Interventional Massachusetts General Hospital · NCT04448327

This study is testing if a new type of nerve stimulation can help people with depression manage stress better, while also looking at how this might differ between men and women.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment80 (estimated)
Ages50 Years to 65 Years
SexAll
SponsorMassachusetts General Hospital Academic / other
Locations1 site (Charlestown, Massachusetts)
Trial IDNCT04448327 on ClinicalTrials.gov

What this trial studies

This study investigates how expiratory-gated transcutaneous vagus nerve stimulation (tVNS) affects the stress response circuitry in individuals with major depressive disorder (MDD), focusing on potential sex differences. A total of 80 adults with recurrent MDD will be randomized to receive either active or sham tVNS during functional magnetic resonance imaging (fMRI) sessions, where their mood and physiological responses will be assessed. The goal is to determine if tVNS can modulate specific brain pathways related to stress and improve physiological outcomes in a sex-dependent manner.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 50 and older with a current or past diagnosis of recurrent major depressive disorder.

Not a fit: Patients with a history of psychosis, severe substance use disorder, or significant cardiovascular or cerebrovascular diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a non-invasive treatment option for managing stress responses in patients with major depressive disorder.

How similar studies have performed: While tVNS has shown beneficial effects in previous studies, this specific approach focusing on sex differences and stress circuitry is novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Current or past diagnosis of recurrent Major Depressive Disorder

Exclusion Criteria:

* 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

Where this trial is running

Charlestown, Massachusetts

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive DisorderAutonomic Nervous SystemTranscutaneous Vagus Nerve StimulationStress Response CircuitryFunctional Magnetic Resonance ImagingSex Differences
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.