Major Depressive DisorderNCT04990687

Vagal Nerve Stimulation for Treatment Resistant Major Depression

A study testing gammaCore™ in people with Major Depressive Disorder, run by University of Alabama at Birmingham at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to 1) explore whether vagal nerve stimulation (nVNS) using a hand- held non-invasive device (gammaCore™) works to treat depression and 2) to confirm gammaCore™'s safety profile. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: gammaCore™
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 1 Jan 2022to 3 Apr 2024
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18-75 years old
Sufficient fluency in English to understand testing procedures and provide written informed consent
A Hamilton Depression Rating Scale total score greater than or equal 18
A DSM 5 diagnosis of MDD based on the MINI

Who cannot join

Evidence of alcohol or other substance use disorder in the past 3 months
For females: current pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy test at screening).
Depressed patients who have failed at least one adequate antidepressant trial during the current depressive episode based on the ATRQ.
Diagnosis of other primary psychiatric disorder (defined in this case as being the main focus of treatment) as determined by the MINI, such as: bipolar disorder, personality disorders, psychotic disorders, post-traumatic stress disorder, obsessive-compulsive disorder, dissociative disorders, eating disorder, or cognitive task due to neurological conditions
Systolic blood pressure < 150 and/or diastolic blood pressure < 90 at screening
Post-partum state (being within 2 months of delivery or miscarriage)

Show all 19Show fewer

Imminent suicide or homicide risk as determined by the investigator
Being treated with one of the following medications: benzodiazepines or other CNS depressants.
No clinically significant neurological disease based on medical history (e.g., epilepsy) or significant head injury.
Any of the following disorders are exclusionary: Rheumatoid arthritis; Lupus erythematosus; Autoimmune hepatitis; Autoimmune peripheral neuropathy; Autoimmune pancreatitis; Behcet's disease; Crohn's disease; Autoimmune glomerulonephritis; Grave's disease; Guillain-Barre syndrome; Hashimoto's thyroiditis; Autoimmune polymyositis or polymyalgia; Myasthenia gravis; Narcolepsy; Polyarteritis nodosa; Scleroderma; Sjogren's syndrome; Transverse myelitis; Wegener's granulomatosis; History of seizures (only childhood febrile seizures are allowed)
The presence of clinically significant laboratory findings in the opinion of the investigator including, but not limited to, clinically significant anemia or transaminase elevation is considered exclusionary.
If the UDS is positive, the subject would be excluded if, in the opinion of the investigator, the positive UDS meant the subject has an active substance use disorder.
Patients with prior exposure to VNS therapy whether using an implantable or external device will be excluded.
An active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device
A metallic device, such as a stent, bone plate, or bone screw, implanted at or near the neck
An open wound, rash, infection, swelling, cut, sore, drug patch, or surgical scar(s) on the neck at the treatment location
Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy)
Patients with clinically significant hypertension, hypotension, bradycardia, or tachycardia

Trial locations and contacts

1 site in 1 country.

United States1 site

The University of Alabama at Birmingham
Birmingham, Alabama, 35294

Other trials in United States

About this study

Read the detailed description

The study will be up to 7 visits, which will occur for up to a 6 month period. The first visit is a screening visit, which will take about one hour to determine eligibility. If participants are eligible, participants will be scheduled for a baseline visit and 6 monthly visits to determine the antidepressant effects and possible side effects.

Conditions: Major Depressive Disorder
Being tested: gammaCore™
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.

gammaCore™Device
Implantable VNS (iVNS), the electrical stimulation of the nervous system to modulate or modify function, has been FDA approved in the United States since the late 1990s. Implantable VNS therapy has been approved for use in epilepsy and depression.
When treating major depression with implanted VNS, the widely held belief is that chronic stimulation is required for therapeutic effect. In trials of implantable VNS in major depression, more patients respond at 12 months than at 3 months. Once depressed patients respond to VNS, the effects have been demonstrated to continue for up to five years with continued stimulation. This finding suggests that VNS gradually changes brain function through neuroplasticity.

Study groups in NCT04990687
Study group	Role	What they receive
Intervention Group	Experimental	Treatment effects will be measured using standard rating scales including the HDRS-17, MADRS, SF-36, CSSR-S, CGI-I, CGI-S, which will be completed at each visit. The following scales will be completed at every other visit following the screening visit: Social Anhedonia Scale, the Motivation and Energy Inventory and the Physical Anhedonia Scale. At each study visit safety assessments including vital sign assessment and adverse event assessment will be completed. Subjects will also undergo physical examination and an ECG for safety during screening, after 8 weeks of treatment and at the end of 12 weeks of treatment. Receives: Device: gammaCore™

What is being measured

The primary outcome is the main question the study is designed to answer.

Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months
Calculated by the Montgomery-Asberg Depression Rating Scale (MADRS): Each item has a severity scale from 0 to 6, with higher scores reflecting more severe symptoms. Ratings can be added to form an overall score (from 0 to 60). Snaith, Harrop, Newby, and Teale (1986) proposed the following cut-offs: scores of 0-6 indicate an absence of symptoms; 7-19 represent mild Depression; 20-34 moderate; 35-60 indicate severe Depression.
Measured: 3 months
Number of Participants With Adverse Events
gammaCore (nVNS) activates the vagus nerve with patented, gentle electrical stimulation. Adverse events were collected for each study participant, and assessed for relatedness to study treatment.
Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 20223 Apr 2024

First posted4 Aug 2021
Study start1 Jan 2022
Primary completion8 Sep 2023
Study completion3 Apr 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by University of Alabama at BirminghamThe 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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04990687
Sponsor's protocol ID: IRB-300007636
Status last verified: Jun 2024
First submitted: 12 Jul 2021
Last updated: 1 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No: To be Determined

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vagal Nerve Stimulation for Treatment Resistant Major Depression
ClinicalTrials.gov ID: NCT04990687
Acronym / sponsor ID: IRB-300007636
Conditions: Major Depressive Disorder
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: University of Alabama at BirminghamUniversity, hospital or other
Study start: 1 Jan 2022 (actual)
Primary completion: 8 Sep 2023 (actual)
Study completion: 3 Apr 2024 (actual)
First posted: 4 Aug 2021 (actual)
Results: Posted 1 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intervention Group	Experimental	Device: gammaCore™Treatment effects will be measured using standard rating scales including the HDRS-17, MADRS, SF-36, CSSR-S, CGI-I, CGI-S, which will be completed at each visit. The following scales will be completed at every other visit following the screening visit: Social Anhedonia Scale, the Motivation and Energy Inventory and the Physical Anhedonia Scale. At each study visit safety assessments including vital sign assessment and adverse event assessment will be completed. Subjects will also undergo physical examination and an ECG for safety during screening, after 8 weeks of treatment and at the end of 12 weeks of treatment.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Age 18-75 years old
Sufficient fluency in English to understand testing procedures and provide written informed consent
A Hamilton Depression Rating Scale total score greater than or equal 18
A DSM 5 diagnosis of MDD based on the MINI

Key exclusion criteria (19 listed)

Evidence of alcohol or other substance use disorder in the past 3 months
For females: current pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy test at screening).
Depressed patients who have failed at least one adequate antidepressant trial during the current depressive episode based on the ATRQ.
Diagnosis of other primary psychiatric disorder (defined in this case as being the main focus of treatment) as determined by the MINI, such as: bipolar disorder, personality disorders, psychotic disorders, post-traumatic stress disorder, obsessive-compulsive disorder, dissociative disorders, eating disorder, or cognitive task due to neurological conditions
Systolic blood pressure < 150 and/or diastolic blood pressure < 90 at screening

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
gammaCore™Implantable VNS (iVNS), the electrical stimulation of the nervous system to modulate or modify function, has been FDA approved in the United States since the late 1990s. Implantable VNS therapy has been approved for use in epilepsy and depression. When treating major depression with implanted VNS, the widely held belief is that chronic stimulation is required for therapeutic effect. In trials of implantable VNS in major depression, more patients respond at 12 months than at 3 months. Once depressed patients respond to VNS, the effects have been demonstrated to continue for up to five years with continued stimulation. This finding suggests that VNS gradually changes brain function through neuroplasticity.	Device	Intervention Group

Primary outcome

Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months
Time frame: 3 months
Calculated by the Montgomery-Asberg Depression Rating Scale (MADRS): Each item has a severity scale from 0 to 6, with higher scores reflecting more severe symptoms. Ratings can be added to form an overall score (from 0 to 60). Snaith, Harrop, Newby, and Teale (1986) proposed the following cut-offs: scores of 0-6 indicate an absence of symptoms; 7-19 represent mild Depression; 20-34 moderate; 35-60 indicate severe Depression.
Number of Participants With Adverse Events
Time frame: 3 months
gammaCore (nVNS) activates the vagus nerve with patented, gentle electrical stimulation. Adverse events were collected for each study participant, and assessed for relatedness to study treatment.

Results and safety

Results posted to the registry on 1 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Intervention Group	5	5

Primary outcome: Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months

Time frame: 3 months. Mean (Standard Deviation). Unit: score on a scale

Measure	Intervention Group n = 5
Value	12.3 (8.6)

Primary outcome: Number of Participants With Adverse Events

Time frame: 3 months. Count of participants. Unit: Participants

Measure	Intervention Group n = 5
Value	1

Population analysed: There were no serious adverse events related to nVNS. One participant required surgery that was unrelated to nVNS and was lost to follow-up after month five. The only adverse event reported was one instance of mild neck soreness which resolved after changing the side to which stimulation was administered.

Adverse events

Time frame: Adverse events data was collected over a 6 month period of enrollment.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Intervention Group	0 of 5 (0%)	1 of 5 (20%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No. To be Determined

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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.

Matthew Macaluso, M.D. principal investigator

The University of Alabama at Birmingham

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing gammaCore™ in people with Major Depressive Disorder, run by University of Alabama at Birmingham 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 4 inclusion and 19 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 Jul 2024. 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. 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?

Yes. Results are posted in the registry (first posted 1 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months (time frame: 3 months). 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?

On the ClinicalTrials.gov record for NCT04990687.

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 Jul 2024.