Vagal Nerve Stimulation for Treatment Resistant Major Depression

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: gammaCore™

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	3 months

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Matthew Macaluso, M.D., The University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): September 8, 2023
• Study Completion (Actual): April 3, 2024

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 27, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: IRB-300007636

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To be Determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes