Deep Brain Stimulation for Treatment Resistant Depression

Phase 1

Recruiting

• Conditions: Treatment Resistant Depression
• Interventions: Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate; Device: Sham stimulation

• Registration Number: NCT04009928
• Lead Sponsor: Sunnybrook Health Sciences Centre

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.

Study Timeline

• Study Start: 2019-06-15
• Study First Submitted: 2019-07-03
• Study First Submitted QC: 2019-07-03
• Study First Posted: 2019-07-05
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-05
• Primary Completion: 2024-12-13
• Study Completion: 2024-12-13

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active followed by sham stimulation	Active stimulation of the medial forebrain bundle or subcallosal cingulate	2 weeks of active stimulation of the medial forebrain bundle or subcallosal cingulate at the optimized stimulation settings derived during the open-label phase. After 1 week of washout period (with no stimulation), subjects undergo 2 weeks of sham stimulation
Active followed by sham stimulation	Sham stimulation	2 weeks of active stimulation of the medial forebrain bundle or subcallosal cingulate at the optimized stimulation settings derived during the open-label phase. After 1 week of washout period (with no stimulation), subjects undergo 2 weeks of sham stimulation
Sham followed by active stimulation	Sham stimulation	2 weeks of sham-stimulation, followed by 2 weeks of active stimulation, separated with 1 week washout period. This is a crossover study, patients will undergo both arms, the order of which they do is randomized.
Sham followed by active stimulation	Active stimulation of the medial forebrain bundle or subcallosal cingulate	2 weeks of sham-stimulation, followed by 2 weeks of active stimulation, separated with 1 week washout period. This is a crossover study, patients will undergo both arms, the order of which they do is randomized.

Primary Outcome Measures

Name	Time	Method
Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively	6 months	Report of all adverse events (minor and major), including perioperative, followup, and stimulation-related
Proportion of responders as measured by the Hamilton Depression Score (17-item version) at 6 months	6 months	Proportion of patients who have a 40% or greater reduction in their Hamilton Depression Score at 6 months compared to their preoperative baseline score.; The Hamilton Depression score is a 17-item score ranging from 0-50, with lower numbers being less severe.

Secondary Outcome Measures

Name	Time	Method
Mean Hamilton Depression Score (17-item version) at the end of the sham-stimulation compared with at the end of the true-stimulation	6 months	At 6 months there is a blinded crossover portion of the study. The Hamilton depressions score will be measured at the end of each of the arms. The score after each arm will be compared.; The Hamilton Depression score is a 17-item score ranging from 0-50, with lower numbers being less severe.
Beck Depression Inventory at 12 months	12 months	Mean Beck Depression Inventory at 12 months compared to mean beck depression inventory at baseline. The Beck Depression Inventory is a 21-item scale with total scores ranging from 0-63, with lower numbers being more severe than higher.
Montgomery Asberg Depression Depression Rating Scale at 12 months	12 months	Proportion of patients with 40% or greater reduction in their Montgomery Asberg Depression Depression Rating Scale at 12 months compared to preoperative baseline. This scale is a 10-item scale with total scores ranging from 0-60, higher numbers being more severe.
Hamilton Depression score (17-item version) at 12 months	12 months	Proportion of patients with 40% or greater decrease in Hamilton Depression Score at 12 months compared to baseline. The Hamilton Depression score is a 17-item score ranging from 0-50, with lower numbers being less severe.
Short Form (36) Health Survey (SF-36) at 12 months	12 months	Comparing mean SF-36 score at 12 months to baseline. The Short-form health survey (36) is a 36-item survey, which produces a total score which is normalized to a score of 0-100 (mean 50), with higher scores indicating a higher quality of life.

Trial Locations

Locations (1)

Sunnybrook Health Sciences Center; 🇨🇦 Toronto, Ontario, Canada