- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04448327
Impact of Transcutaneous Vagal Nerve Stimulation on Stress Response in Major Depression (tVNS_MDD_Sex)
March 13, 2023 updated by: Ronald Garcia, Massachusetts General Hospital
Sex-Dependent Impact of Transcutaneous Vagal Nerve Stimulation on the Stress Response Circuitry and Autonomic Dysregulation in Major Depression
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
Major depressive disorder (MDD) is a leading cause of morbidity and disability worldwide with abnormalities in the stress response circuitry and central autonomic network.
Many of these regions are sexually dimorphic and related with sex differences in mood and hypothalamic-pituitary-adrenal (HPA) axis modulation, the dysregulation of which is associated with alterations of hormone and immune responses to stress, autonomic dysfunction and increased cardiovascular risk.
The primary goal of this study is to use non-invasive neuromodulatory stimulation of the vagus to target the circuitry associated with stress-immune function and map its neuroanatomic and physiological effects in MDD by sex.
Vagal nerve stimulation (VNS), FDA-approved for MDD, modulates brain circuitry implicated in mood/anxiety and autonomic regulation, however, it is implanted and thus invasive.
We propose the use of a physiologically-enhanced transcutaneous VNS (tVNS) as a low risk, non-invasive, and inexpensive alternative.
While tVNS has had beneficial effects on depressive symptomatology and autonomic regulation, current stimulation parameters are based on historical iVNS data that included mostly male populations.
We propose that tVNS effects on the regulation of specific brainstem-cortical pathways is modulated by sex.
Moreover, as the dorsal medullary vagal system operates in tune with respiration, we recently demonstrated that tVNS can be optimized by gating stimulation to respiration.
Thus, this study proposes to identify the sex-dependent impact of expiratory-gated tVNS on the modulation of stress response circuitry alterations and physiological dysregulation of recurrent MDD.
We will evaluate a sample of 80 adults with recurrent MDD randomized to receive active tVNS or sham stimulation during a functional magnetic resonance imaging (fMRI) session.
The fMRI session will include a stress challenge designed to elicit a sympatho-excitatory state, with simultaneous mood and physiological assessments, including hormonal and dynamic cardiovagal heart rate variability (HRV) evaluations.
We hypothesize that expiratory-gated tVNS will effectively modulate specific brainstem-cortical pathways of the stress response circuitry and will attenuate physiological deficits of recurrent MDD patients.
We further hypothesize that tVNS will impact brain activity and physiology in sex-dependent ways.
Study Type
Interventional
Enrollment (Anticipated)
80
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Ronald G Garcia, MD, PhD
- Phone Number: 617-643-4265
- Email: rgarciagomez@mgh.harvard.edu
Study Contact Backup
- Name: Vitaly Napadow, PhD
- Phone Number: 617-724-3402
- Email: vitaly@mgh.harvard.edu
Study Locations
-
-
Massachusetts
-
Charlestown, Massachusetts, United States, 02129
- Recruiting
- Massachusetts General Hospital
-
Contact:
- Ronald G Garcia, MD, PhD
- Phone Number: 617-643-4265
- Email: rgarciagomez@mgh.harvard.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active tVNS
Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle
|
non-painful electrical stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session
Other Names:
|
Sham Comparator: Sham tVNS
Sham transcutaneous vagus nerve stimulation on the left auricle
|
Sham stimulation of the auricle for 30 minutes during a functional magnetic resonance imaging session
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain activity during functional magnetic resonance imaging (fMRI)
Time Frame: 1 hour
|
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)
Time Frame: 1 hour
|
Changes in cardiac autonomic function (High Frequency power-Heart Rate Variability) between active and sham tVNS.
|
1 hour
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in serum cortisol levels
Time Frame: 2 hours
|
Changes in serum cortisol levels from baseline to post-stimulation will be assessed and compared between active and sham tVNS
|
2 hours
|
Change in serum levels of pro-inflammatory cytokines
Time Frame: 2 hours
|
Changes in serum levels of proinflammatory cytokines (IL1B, IL6, TNF alfa) from baseline to post-stimulation will be assessed and compared between active and sham tVNS
|
2 hours
|
Change in depressive symptoms assessed by the Beck Depression Inventory
Time Frame: 2 hours
|
Changes from baseline to post-stimulation in the score of the Beck Depression Inventory will be compared between active and sham tVNS.
(Beck depression inventory minimum score= 0, maximum score= 63; higher total scores indicate more severe depressive symptoms)
|
2 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Ronald G Garcia, MD, PhD, Massachusetts General Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 29, 2021
Primary Completion (Anticipated)
July 15, 2024
Study Completion (Anticipated)
November 15, 2024
Study Registration Dates
First Submitted
June 17, 2020
First Submitted That Met QC Criteria
June 24, 2020
First Posted (Actual)
June 25, 2020
Study Record Updates
Last Update Posted (Actual)
March 15, 2023
Last Update Submitted That Met QC Criteria
March 13, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2020P001212
- 1U54MH118919-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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