Deep Brain Stimulation for Treatment Resistant Depression

NCT ID: NCT04009928

Last Updated: 2023-12-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-15

Study Completion Date

2024-12-13

Brief Summary

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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

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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.

Conditions

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Treatment Resistant Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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 Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
An independent researcher will perform the randomization and institute the sham/active stimulation, allowing for continued blinding of participants/care providers/investigators/outcomes assessors.

Study Groups

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Active followed by 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

Group Type EXPERIMENTAL

Active stimulation of the medial forebrain bundle or subcallosal cingulate

Intervention Type DEVICE

Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate

Sham stimulation

Intervention Type DEVICE

Sham stimulation for 2 weeks (Cross-over design)

Sham followed by active 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.

Group Type SHAM_COMPARATOR

Active stimulation of the medial forebrain bundle or subcallosal cingulate

Intervention Type DEVICE

Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate

Sham stimulation

Intervention Type DEVICE

Sham stimulation for 2 weeks (Cross-over design)

Interventions

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Active stimulation of the medial forebrain bundle or subcallosal cingulate

Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate

Intervention Type DEVICE

Sham stimulation

Sham stimulation for 2 weeks (Cross-over design)

Intervention Type DEVICE

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sunnybrook Health Sciences Centre

OTHER

Sponsor Role lead

Responsible Party

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Dr. Nir Lipsman

Surgeon-Scientist

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Sunnybrook Health Sciences Center

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Anusha Baskaran, PhD

Role: CONTACT

Email: [email protected]

Facility Contacts

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Benjamin Davidson, MD

Role: primary

Sachie Sharma, BSc

Role: backup

Other Identifiers

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277-2018

Identifier Type: -

Identifier Source: org_study_id