Major Depressive DisorderNCT04607226
Effects of Respiratory-Gated Transcutaneous Vagal Nerve Stimulation in Major Depression (Phase 1)
A study testing Active transcutaneous vagus nerve stimulation in people with Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 45 years, women only
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Active transcutaneous vagus nerve stimulation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2020to 12 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
About this study
Official title: A Translational Approach to Cardiorespiratory-Gated Stimulation of the Auricular Branch of the Vagus Nerve for the Treatment of Major Depression
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.
Read the 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.
- Conditions
- Major Depressive Disorder
- Being tested
- Active transcutaneous vagus nerve stimulation, Sham transcutaneous vagus nerve stimulation
- Keywords
- Transcutaneous Vagus Nerve Stimulation, Cardiac autonomic function, Depressive symptomatology
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active transcutaneous vagus nerve stimulationOther
Also called Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), transcutaneous vagus nerve stimulation
respiratory-gated non-painful electrical stimulation of the auricle for 30 minutes
Sham transcutaneous vagus nerve stimulationOther
Also called transcutaneous vagus nerve stimulation
stimulation of the auricle for 30 minutes
| Study group | Role | What they receive |
|---|---|---|
| Active tVNS - 2 Hz | Experimental | Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 2 Hz stimulation frequency Receives: Other: Active transcutaneous vagus nerve stimulation |
| Active tVNS - 8 Hz | Experimental | Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 8 Hz stimulation frequency Receives: Other: Active transcutaneous vagus nerve stimulation |
| Active tVNS - 30 Hz | Experimental | Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 30 Hz stimulation frequency Receives: Other: Active transcutaneous vagus nerve stimulation |
| Active tVNS - 100 Hz | Experimental | Expiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 100 Hz stimulation frequency Receives: Other: Active transcutaneous vagus nerve stimulation |
| Sham tVNS | Sham comparator | Sham transcutaneous vagus nerve stimulation on the left auricle Receives: Other: Sham transcutaneous vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac autonomic function
Changes in cardiac autonomic function (High Frequency power-Heart Rate Variability) between active and sham tVNS.
Measured: 1 hour
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)
Measured: 1 hour
Secondary outcomes (1)
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
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start2 Nov 2020
- Primary completion12 Oct 2022
- Study completion12 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Responsible party
- Principal investigator, Ronald Garcia, Massachusetts General Hospital
- Investigators
- Ronald G Garcia, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04607226
- Sponsor's protocol ID
- 2019P003698
- Other IDs
- 26236
- Status last verified
- Jul 2023
- First submitted
- 22 Oct 2020
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Translational Approach to Cardiorespiratory-Gated Stimulation of the Auricular Branch of the Vagus Nerve for the Treatment of Major Depression
- ClinicalTrials.gov ID
- NCT04607226
- Acronym / sponsor ID
- 2019P003698
- Conditions
- Major Depressive Disorder
- Keywords
- Transcutaneous Vagus Nerve Stimulation, Cardiac autonomic function, Depressive symptomatology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 12 Oct 2022 (actual)
- First posted
- 29 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Active tVNS - 2 Hz | Experimental | Other: Active transcutaneous vagus nerve stimulationExpiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 2 Hz stimulation frequency |
| Active tVNS - 8 Hz | Experimental | Other: Active transcutaneous vagus nerve stimulationExpiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 8 Hz stimulation frequency |
| Active tVNS - 30 Hz | Experimental | Other: Active transcutaneous vagus nerve stimulationExpiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 30 Hz stimulation frequency |
| Active tVNS - 100 Hz | Experimental | Other: Active transcutaneous vagus nerve stimulationExpiratory-gated transcutaneous vagus nerve stimulation on the left auricle with 100 Hz stimulation frequency |
| Sham tVNS | Sham comparator | Other: Sham transcutaneous vagus nerve stimulationSham transcutaneous vagus nerve stimulation on the left auricle |
Who may qualify
- Ages
- 24 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active transcutaneous vagus nerve stimulationAlso: Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS), transcutaneous vagus nerve stimulationrespiratory-gated non-painful electrical stimulation of the auricle for 30 minutes | Other | Active tVNS - 100 Hz, Active tVNS - 2 Hz, Active tVNS - 30 Hz, Active tVNS - 8 Hz |
| Sham transcutaneous vagus nerve stimulationAlso: transcutaneous vagus nerve stimulationstimulation of the auricle for 30 minutes | Other | Sham tVNS |
Primary outcome
Cardiac autonomic function
Time frame: 1 hour
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
Time frame: 1 hour
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)
1 secondary outcome
Change in serum levels of pro-inflammatory cytokines
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald G Garcia, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active transcutaneous vagus nerve stimulation in people with Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac autonomic function (time frame: 1 hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.