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Deep Brain Stimulation for Treatment Resistant Depression

Primary Purpose

Treatment Resistant Depression

Status
Unknown status
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Active stimulation of the medial forebrain bundle or subcallosal cingulate
Sham stimulation
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Treatment Resistant Depression

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sunnybrook Health Sciences CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active followed by sham stimulation

Sham followed by active stimulation

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively
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
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

Mean Hamilton Depression Score (17-item version) at the end of the sham-stimulation compared with at the end of the true-stimulation
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.
Hamilton Depression score (17-item version) at 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.
Montgomery Asberg Depression Depression Rating Scale at 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.
Beck Depression Inventory at 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.
Short Form (36) Health Survey (SF-36) at 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.

Full Information

First Posted
July 3, 2019
Last Updated
March 15, 2021
Sponsor
Sunnybrook Health Sciences Centre
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1. Study Identification

Unique Protocol Identification Number
NCT04009928
Brief Title
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 15, 2019 (Actual)
Primary Completion Date
December 13, 2021 (Anticipated)
Study Completion Date
December 13, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
An independent researcher will perform the randomization and institute the sham/active stimulation, allowing for continued blinding of participants/care providers/investigators/outcomes assessors.
Allocation
Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active followed by sham stimulation
Arm Type
Experimental
Arm Description
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
Arm Title
Sham followed by active stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Active stimulation of the medial forebrain bundle or subcallosal cingulate
Intervention Description
Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate
Intervention Type
Device
Intervention Name(s)
Sham stimulation
Intervention Description
Sham stimulation for 2 weeks (Cross-over design)
Primary Outcome Measure Information:
Title
Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively
Description
Report of all adverse events (minor and major), including perioperative, followup, and stimulation-related
Time Frame
6 months
Title
Proportion of responders as measured by the Hamilton Depression Score (17-item version) at 6 months
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Mean Hamilton Depression Score (17-item version) at the end of the sham-stimulation compared with at the end of the true-stimulation
Description
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.
Time Frame
6 months
Title
Hamilton Depression score (17-item version) at 12 months
Description
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.
Time Frame
12 months
Title
Montgomery Asberg Depression Depression Rating Scale at 12 months
Description
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.
Time Frame
12 months
Title
Beck Depression Inventory at 12 months
Description
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.
Time Frame
12 months
Title
Short Form (36) Health Survey (SF-36) at 12 months
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women ≥20 and ≤80 years of age. 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. DSM-V diagnosis of major depressive disorder or bipolar II, 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. A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed) 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: Failed to respond or tolerate adequate trial of three or more medications accepted as first line in the treatment of depression Failed to respond or tolerate augmentation with or combination of at least 2 medications known to be first line treatments for depression An adequate trial of cognitive behavioural therapy or other evidence-supported psychotherapy, delivered by a therapist experienced in treating depression A consistent dose of any and all medications in the 30 days prior to study entry. Women of childbearing potential must agree to use a contraception method throughout the study. Exclusion Criteria: Past or current evidence of psychosis or mania Active neurologic disease, such as epilepsy Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine Current active suicidal ideation Any contraindication to MRI scanning Presence of significant cognitive impairment Likely to relocate or move out of the country during the study's duration Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anusha Baskaran, PhD
Email
Anusha.baskaran@sunnybrook.ca
Facility Information:
Facility Name
Sunnybrook Health Sciences Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Davidson, MD
Email
benjamin.davidson@mail.utoronto.ca
First Name & Middle Initial & Last Name & Degree
Sachie Sharma, BSc
Phone
416-480-6100 x3254
Email
sachie.sharma@sunnybrook.ca

12. IPD Sharing Statement

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Deep Brain Stimulation for Treatment Resistant Depression

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