Vagal Nerve Stimulation for Treatment Resistant Major Depression

Major Depressive Disorder Clinical Trial

Official title:

Vagal Nerve Stimulation for Treatment Resistant Major Depression

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04990687
• Other study ID #: IRB-300007636
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: April 1, 2024

Study information

• Verified date: January 2024
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: April 1, 2024
• Est. primary completion date: September 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	The University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antidepressant effects of nVNS in humans	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
Primary	Incidence of gammaCore™ Adverse Events	gammaCore (nVNS) activates the vagus nerve with patented, gentle electrical stimulation.; To assess potential changes in cognition, three computerized tests of cognition will the administered at baseline, Week 8, and Week 12. The Relational & Item Specific Encoding task (RISE) will probe any potential neural abnormalities. The Probabilistic Learning Task will be used to examine neural circuits related to reward processing in major depression disorder. For the working memory task, participants will be shown two images with objects and asked to decide whether the two images differ or not.	3 months