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Effects of Respiratory-Gated Transcutaneous Vagal Nerve Stimulation in Major Depression (Phase 1)

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active transcutaneous vagus nerve stimulation
Sham transcutaneous vagus nerve stimulation
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Major Depressive Disorder focused on measuring Transcutaneous Vagus Nerve Stimulation, Cardiac autonomic function, Depressive symptomatology

Eligibility Criteria

24 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of recurrent Major Depressive Disorder with a current active depressive episode
  • Currently not taking psychiatric medications or on a stable therapeutic dose of psychiatric medication for at least 30 days prior to entering the study

Exclusion Criteria:

  • History of cardio-, cerebro-, or peripheral vascular disease, diabetes mellitus, morbid obesity (BMI > 40 kg/m2), kidney or liver failure, history of unexplained fainting spells
  • Any psychiatric disorder involving a history of psychosis (e.g. schizophrenia, bipolar disorders, severe personality disorders)
  • Any chronic condition affecting movement, speech and/or ability to read or follow written instructions
  • Substance use disorder, either mild, moderate, or severe within the past 12 months (excludes nicotine)
  • History of suicide attempt within the last year or current active suicidal ideation
  • History of a clinically defined neurological disorder including, but not limited to: Any condition likely to be associated with increased intracranial pressure; space occupying brain lesion; History of cerebrovascular accident; Transient ischemic attack within two years; Cerebral aneurysm; Dementia; Parkinson's Disease; Huntington's chorea; or Multiple sclerosis.
  • Pregnant or nursing
  • Metallic implants or devices contraindicating tVNS

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Sham Comparator

Arm Label

Active tVNS - 2 Hz

Active tVNS - 8 Hz

Active tVNS - 30 Hz

Active tVNS - 100 Hz

Sham tVNS

Arm Description

Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 2 Hz stimulation frequency

Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 8 Hz stimulation frequency

Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 30 Hz stimulation frequency

Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 100 Hz stimulation frequency

Sham transcutaneous vagus nerve stimulation on the left auricle

Outcomes

Primary Outcome Measures

Cardiac autonomic function
Changes in cardiac autonomic function (High Frequency power-Heart Rate Variability) between active and sham tVNS.
Change in depressive symptoms assessed by the Beck Depression Inventory
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)

Secondary Outcome Measures

Change in serum levels of pro-inflammatory cytokines
Changes in serum levels of proinflammatory cytokines (Interleukin 1B, Interleukin 6, Tumor necrosis factor alfa) from baseline to post-stimulation will be assessed and compared between active and sham tVNS

Full Information

First Posted
October 22, 2020
Last Updated
July 28, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Brain & Behavior Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04607226
Brief Title
Effects of Respiratory-Gated Transcutaneous Vagal Nerve Stimulation in Major Depression (Phase 1)
Official Title
A Translational Approach to Cardiorespiratory-Gated Stimulation of the Auricular Branch of the Vagus Nerve for the Treatment of Major Depression
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
November 2, 2020 (Actual)
Primary Completion Date
October 12, 2022 (Actual)
Study Completion Date
October 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Brain & Behavior Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate the short term effects of respiratory-gated transcutaneous vagus nerve stimulation on the regulation of cardiovagal activity, depressive symptomatology and immune function in subjects with major depression and determine the optimal stimulation frequency for this population.
Detailed Description
This study will compare the acute effects of respiratory-gated transcutaneous vagus nerve stimulation (tVNS) at different stimulation frequencies and sham stimulation during five sessions within a 2 week period. Heart rate variability (HRV) point process adaptive filtering estimation algorithms will be used to evaluate changes in cardiac autonomic physiology in subjects with major depression in response to tVNS. The effects of tVNS on cardiovagal regulation will be evaluated at rest and in response to an emotion reactivity task. Depression rating scales (Beck's Depression Inventory) will be used to evaluate short term effects of tVNS on depressive symptoms in these subjects. In addition, the study will evaluate the acute effects of the stimulation on serum levels of pro-inflammatory cytokines. The stimulation frequency that produces the greatest regulatory effects on depressive symptoms and physiological variables in this population will be used in a second longitudinal phase of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Transcutaneous Vagus Nerve Stimulation, Cardiac autonomic function, Depressive symptomatology

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active tVNS - 2 Hz
Arm Type
Experimental
Arm Description
Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 2 Hz stimulation frequency
Arm Title
Active tVNS - 8 Hz
Arm Type
Experimental
Arm Description
Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 8 Hz stimulation frequency
Arm Title
Active tVNS - 30 Hz
Arm Type
Experimental
Arm Description
Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 30 Hz stimulation frequency
Arm Title
Active tVNS - 100 Hz
Arm Type
Experimental
Arm Description
Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 100 Hz stimulation frequency
Arm Title
Sham tVNS
Arm Type
Sham Comparator
Arm Description
Sham transcutaneous vagus nerve stimulation on the left auricle
Intervention Type
Other
Intervention Name(s)
Active transcutaneous vagus nerve stimulation
Other Intervention Name(s)
Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), transcutaneous vagus nerve stimulation
Intervention Description
respiratory-gated non-painful electrical stimulation of the auricle for 30 minutes
Intervention Type
Other
Intervention Name(s)
Sham transcutaneous vagus nerve stimulation
Other Intervention Name(s)
transcutaneous vagus nerve stimulation
Intervention Description
stimulation of the auricle for 30 minutes
Primary Outcome Measure Information:
Title
Cardiac autonomic function
Description
Changes in cardiac autonomic function (High Frequency power-Heart Rate Variability) between active and sham tVNS.
Time Frame
1 hour
Title
Change in depressive symptoms assessed by the Beck Depression Inventory
Description
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)
Time Frame
1 hour
Secondary Outcome Measure Information:
Title
Change in serum levels of pro-inflammatory cytokines
Description
Changes in serum levels of proinflammatory cytokines (Interleukin 1B, Interleukin 6, Tumor necrosis factor alfa) from baseline to post-stimulation will be assessed and compared between active and sham tVNS
Time Frame
2 hours

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
24 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of recurrent Major Depressive Disorder with a current active depressive episode Currently not taking psychiatric medications or on a stable therapeutic dose of psychiatric medication for at least 30 days prior to entering the study Exclusion Criteria: History of cardio-, cerebro-, or peripheral vascular disease, diabetes mellitus, morbid obesity (BMI > 40 kg/m2), kidney or liver failure, history of unexplained fainting spells Any psychiatric disorder involving a history of psychosis (e.g. schizophrenia, bipolar disorders, severe personality disorders) Any chronic condition affecting movement, speech and/or ability to read or follow written instructions Substance use disorder, either mild, moderate, or severe within the past 12 months (excludes nicotine) History of suicide attempt within the last year or current active suicidal ideation History of a clinically defined neurological disorder including, but not limited to: Any condition likely to be associated with increased intracranial pressure; space occupying brain lesion; History of cerebrovascular accident; Transient ischemic attack within two years; Cerebral aneurysm; Dementia; Parkinson's Disease; Huntington's chorea; or Multiple sclerosis. Pregnant or nursing Metallic implants or devices contraindicating tVNS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald G Garcia, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Charlestown
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Effects of Respiratory-Gated Transcutaneous Vagal Nerve Stimulation in Major Depression (Phase 1)

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