Deep Brain Stimulation for Treatment Resistant Depression

NCT04009928 | Unknown Phase 1

• 1 other identifier: 277-2018
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (2)

• 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

  6 months

• 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.

  6 months

Secondary Outcomes (5)

• 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

• Hamilton Depression score (17-item version) at 12 months

  12 months

• Montgomery Asberg Depression Depression Rating Scale at 12 months

  12 months

• Beck Depression Inventory at 12 months

  12 months

• Short Form (36) Health Survey (SF-36) at 12 months

  12 months

Study Arms (2)

Active followed by sham stimulation

EXPERIMENTAL

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

Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate; Device: Sham stimulation

Sham followed by active stimulation

SHAM COMPARATOR

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.

Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate; Device: Sham stimulation

Interventions

Active stimulation of the medial forebrain bundle or subcallosal cingulate DEVICE

Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate

Active followed by sham stimulation; Sham followed by active stimulation

Sham stimulation DEVICE

Sham stimulation for 2 weeks (Cross-over design)

Active followed by sham stimulation; Sham followed by active stimulation

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Center

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Anusha Baskaran, PhD

CONTACT

Anusha.baskaran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An independent researcher will perform the randomization and institute the sham/active stimulation, allowing for continued blinding of participants/care providers/investigators/outcomes assessors.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgeon-Scientist

Model Details: 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.

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 5, 2019
• Study Start: June 15, 2019
• Primary Completion: December 13, 2024
• Study Completion: December 13, 2024
• Last Updated: December 5, 2023

Record last verified: 2023-12

Locations

CA (1)