Vagal Nerve Stimulation for Treatment Resistant Major Depression

NCT ID: NCT04990687

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2024-04-03

Brief 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention Group

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.

Group Type: EXPERIMENTAL

gammaCore™

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Age 18-75 years old

2. Sufficient fluency in English to understand testing procedures and provide written informed consent

3. A Hamilton Depression Rating Scale total score greater than or equal 18

4. A DSM 5 diagnosis of MDD based on the MINI

Exclusion Criteria

1. Evidence of alcohol or other substance use disorder in the past 3 months

2. For females: current pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy test at screening).

3. Depressed patients who have failed at least one adequate antidepressant trial during the current depressive episode based on the ATRQ.

4. 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

5. Systolic blood pressure < 150 and/or diastolic blood pressure < 90 at screening

6. Post-partum state (being within 2 months of delivery or miscarriage)

7. Imminent suicide or homicide risk as determined by the investigator

8. Being treated with one of the following medications: benzodiazepines or other CNS depressants.

9. No clinically significant neurological disease based on medical history (e.g., epilepsy) or significant head injury.

10. 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)

11. 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.

12. 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.

13. Patients with prior exposure to VNS therapy whether using an implantable or external device will be excluded.

14. An active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device

15. A metallic device, such as a stent, bone plate, or bone screw, implanted at or near the neck

16. An open wound, rash, infection, swelling, cut, sore, drug patch, or surgical scar(s) on the neck at the treatment location

17. Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)

18. Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy)

19. Patients with clinically significant hypertension, hypotension, bradycardia, or tachycardia

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Matthew Macaluso

Bee McWane Reid Professor, Department of Psychiatry and Behavioral Neurobiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matthew Macaluso, M.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Alabama at Birmingham

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IRB-300007636

Identifier Type: -

Identifier Source: org_study_id