Major Depressive Disorder
Conditions
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.
Interventions
DEVICEgammaCore™
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.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
Potential study participant pre-screening and recruitment activities were initiated January 1, 2022. The first study participant was screened May 5, 2022, and enrolled May 27, 2022. The last study participant was screened March 7, 2023, and enrolled March 10, 2023. Potential participants were recruited from the outpatient clinic at UAB and in the surrounding community.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Intervention Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
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.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Montgomery-Asberg Depression Rating Scale (MADRS) at 3 Months | 12.3 score on a scale | Standard Deviation 8.6 |
Primary
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.
Time frame: 3 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Number of Participants With Adverse Events | 1 Participants |