Vagus Nerve Stimulation: Integration of Behavior and Cardiac Modulation

NCT04467164 | Completed Results

• 2 other identifiers: 2013P001259R21MH103468
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study characterized the impact of respiratory-gated transcutaneous vagus nerve stimulation (tVNS) on the modulation of the stress response circuitry, vagal tone and depressed mood in patients with major depressive disorder (MDD). Twenty premenopausal women with recurrent MDD in an active episode were recruited into a single-blind cross-over study that included two functional MRI visits within a one week period with simultaneous mood and physiological assessments. Randomization to exhalatory- or inhalatory-gated tVNS was performed to control for order effects. The study hypothesis was that exhalatory-gated tVNS would have a significantly greater impact on the regulation of brain activity in stress response circuitry, vagal tone and depressed mood in MDD patients compared to inhalation-gated tVNS. This is not a clinical trial aimed to test a medical device, but a basic experimental study oriented to understand the effects of vagal afference modulation on brain and cardiovagal physiological response to stress in major depression.

Conditions

Major Depressive Disorder

Keywords

Transcutaneous vagus nerve stimulation; Stress response circuitry; functional magnetic resonance imaging; respiration; depression

Outcome Measures

Primary Outcomes (1)

• Brain Activity Changes (Average Differences in Beta Weights From Significantly Activated Regions: Post-stimulation Minus Pre-stimulation) Evaluated Using Functional Magnetic Resonance Imaging.

  A functional magnetic resonance imaging (fMRI) analysis was used to evaluate changes in brain activity \[blood oxygenation level-dependent (BOLD) signal\] in response to a visual stress challenge (post- and pre-stimulation). For this analysis a General Lineal Model analsysis with the statistical parametrical software (SPM) was used to model the change in BOLD signals during exposure to negative vs neutral images of the stress tasks. A voxel-wise height threshold of p \< 0.001, and a cluster correction with FWE p-value\<0.05 was used to identify brain areas with significant activation in response to the task. Mean beta weights within each significant cluster were extracted for each participant, and average differences in beta weights (Post minus Pre stimulation) were estimated for each group. A positive difference indicates increased activation of a particular brain region in response to the stimulation, whereas a negative difference indicates a reduction in brain activity.

  1 hour

Secondary Outcomes (2)

• Change in Depressive Symptoms Assessed by the Beck Depression Inventory (1 Hour Post Intervention Minus Baseline)

  2 hours

• Changes in Cardiac Autonomic Function (Percent Change in Normalized High-frequency Power of Heart Rate Variability (HFn-HRV): Post-stimulation Versus Pre-stimulation)

  1 hour

Study Arms (2)

Exhalatory-gated tVNS

EXPERIMENTAL

exhalatory-gated tVNS on the left auricle

Other: exhalatory-gated transcutaneous vagus nerve stimulation (e-RAVANS)

Inhalatory-gated tVNS

ACTIVE COMPARATOR

inhalatory-gated tVNS on the left auricle

Other: Inhalatory-gated transcutaneous vagus nerve stimulation (i-RAVANS)

Interventions

exhalatory-gated transcutaneous vagus nerve stimulation (e-RAVANS) OTHER

Non-painful exhalatory-gated electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session.

Also known as: e-RAVANS

Exhalatory-gated tVNS

Inhalatory-gated transcutaneous vagus nerve stimulation (i-RAVANS) OTHER

Non-painful inhalatory-gated electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session.

Also known as: i-RAVANS

Inhalatory-gated tVNS

Eligibility Criteria

• Age: 25 Years - 40 Years
• Gender Eligibility Details: premenopausal women only
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• History of Axis I psychiatric diagnosis other than MDD or anxiety disorder - e.g., substance use disorder, psychotic disorder, or bipolar disorder.
• Current Suicidal Ideation with intent and/or plan or history of suicide attempt within the last year
• Use of psychotropic medications within four weeks prior to study with the exception of Selective Serotonin Reuptake Inhibitors (SSRIs) and Selective Norepinephrine Reuptake Inhibitors (SNRIs) class of antidepressant medication only
• Use of Tricyclic antidepressants (TCAs), Monoamine oxidase inhibitors (MAOIs), and Atypical agents
• History of cardiovascular disease
• History of neuroleptic use
• Past history of substance abuse or dependence within the past 12 months (excludes nicotine)
• Bleeding disorder or use of anticoagulants.
• Pregnancy
• Metallic implants or devices contraindicating magnetic resonance imaging.
• Use of beta blockers

Sponsors & Collaborators

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

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Respiratory Aspiration; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Jill M. Goldstein
• Organization: Massachusetts General Hospital, Harvard Medical School

jill_goldstein@hms.harvard.edu

617-724-3776

Study Officials

• Jill M Goldstein, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Exec. Dir. Innovation Center on Sex Differences in Medicine

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 10, 2020
• Study Start: April 15, 2015
• Primary Completion: September 15, 2018
• Study Completion: September 22, 2018
• Last Updated: March 27, 2025
• Results First Posted: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)