Clinical trial NCT04009928: Deep Brain Stimulation for Treatment Resistant Depression
Official title: Deep Brain Stimulation of the Medial Forebrain Bundle and Subcallosal Cingulate for the Treatment of Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Treatment Resistant Depression
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: After 6 months of open-label stimulation, patients will enter a blinded, randomized, crossover phase. After a 1 week washout phase with stimulation turned OFF, patients will randomly be assigned to receive 2 weeks of sham stimulation followed by 2 weeks of active stimulation (at their optimized settings), or vice versa.
Primary purpose: TREATMENT

Brief summary: Treatment resistant depression (TRD) is a major global health concern, and there is a crucial need to develop novel effective treatments.

The medial forebrain bundle (MFB) is a recently described DBS target, with reported rapid onset of antidepressant effects. A recent small randomized trial reported a 100% response rate. The subcallosal cingulate cortex (SCC) is the most commonly used target in DBS for depression.

Herein, the investigators will conduct a sham-controlled randomized trial of DBS to the MFB or SCC for TRD.

Detailed description: Eight patients with TRD will be treated with DBS to the MFB. At approximately 2 weeks postoperartively, stimulation will be initiated in all patients. Voltage and contact position will be altered initially, looking for optimal and stabilized responses in depressive symptoms, while trying to minimize any side effects.

Following this 6 month open-label optimization phase, patients will be then undergo randomization to receive 2 weeks of stimulation followed by 2 weeks of sham stimulation, or vice versa. These 2 week phases will be separated by a 1 week washout period. Depressive symptoms will be evaluated at the end of each 2 week phase, then patients will resume open-label stimiulation.

Eligibility criteria: Inclusion Criteria:

1. Men and women ≥20 and ≤80 years of age.
2. Patients who are able and willing to give consent and physically and practically able to attend study visits, as determined by both study Psychiatrist and the surgeon.
3. DSM-V diagnosis of major depressive disorder or bipolar II,
4. At least 5-year illness history of the primary disorder and at least 6 months since the onset of the first episode of major depression.
5. A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed)
6. Medication-refractoriness as determined by an adequate dose and duration of standard psychiatric treatments (including psychotherapy and/or pharmacology) as determined by two psychiatrists associated with the study. Including specifically:

   1. Failed to respond or tolerate adequate trial of three or more medications accepted as first line in the treatment of depression
   2. Failed to respond or tolerate augmentation with or combination of at least 2 medications known to be first line treatments for depression
   3. An adequate trial of cognitive behavioural therapy or other evidence-supported psychotherapy, delivered by a therapist experienced in treating depression
7. A consistent dose of any and all medications in the 30 days prior to study entry.
8. Women of childbearing potential must agree to use a contraception method throughout the study.

Exclusion Criteria:

1. Past or current evidence of psychosis or mania
2. Active neurologic disease, such as epilepsy
3. Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine
4. Current active suicidal ideation
5. Any contraindication to MRI scanning
6. Presence of significant cognitive impairment
7. Likely to relocate or move out of the country during the study's duration
8. Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure.
9. Currently pregnant (as determined by history and serum HCG) or lactating; for females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation

Primary outcomes:
measure: Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively
timeFrame: 6 months
measure: Proportion of responders as measured by the Hamilton Depression Score (17-item version) at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Mean Hamilton Depression Score (17-item version) at the end of the sham-stimulation compared with at the end of the true-stimulation
timeFrame: 6 months
measure: Hamilton Depression score (17-item version) at 12 months
timeFrame: 12 months
measure: Montgomery Asberg Depression Depression Rating Scale at 12 months
timeFrame: 12 months
measure: Beck Depression Inventory at 12 months
timeFrame: 12 months
measure: Short Form (36) Health Survey (SF-36) at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
Study officials:
References: