Treatment Resistant DepressionPhase 1/2NCT04009928
Deep Brain Stimulation for Treatment Resistant Depression
A Phase 1/2 study testing Active stimulation of the medial forebrain bundle or subcallosal cingulate in people with Treatment Resistant Depression, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Active stimulation of the medial forebrain bundle or subcallosal cingulate
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 15 Jun 2019to 13 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Anusha Baskaran, PhD contact
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Center
Toronto, Ontario, M4N 3M5
Benjamin Davidson, MD, benjamin.davidson@mail.utoronto.ca
Sachie Sharma, BSc, 416-480-6100 x3254, sachie.sharma@sunnybrook.ca
About this study
Official title: Deep Brain Stimulation of the Medial Forebrain Bundle and Subcallosal Cingulate for the Treatment of Treatment Resistant Depression
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.
Read the 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.
- Conditions
- Treatment Resistant Depression
- Being tested
- Active stimulation of the medial forebrain bundle or subcallosal cingulate, Sham stimulation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active stimulation of the medial forebrain bundle or subcallosal cingulateDevice
Deep brain stimulation of the medial forebrain bundle or subcallosal cingulate
Sham stimulationDevice
Sham stimulation for 2 weeks (Cross-over design)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate; Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
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.
Measured: 6 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start15 Jun 2019
- Primary completion13 Dec 2024 (estimated)
- Study completion13 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Nir Lipsman, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009928
- Sponsor's protocol ID
- 277-2018
- Status last verified
- Dec 2023
- First submitted
- 3 Jul 2019
- Last updated
- 5 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation of the Medial Forebrain Bundle and Subcallosal Cingulate for the Treatment of Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT04009928
- Acronym / sponsor ID
- 277-2018
- Conditions
- Treatment Resistant Depression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 15 Jun 2019 (actual)
- Primary completion
- 13 Dec 2024 (estimated)
- Study completion
- 13 Dec 2024 (estimated)
- First posted
- 5 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active followed by sham stimulation | Experimental | Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate, Device: Sham stimulation2 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 comparator | Device: Active stimulation of the medial forebrain bundle or subcallosal cingulate, Device: Sham stimulation2 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. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active stimulation of the medial forebrain bundle or subcallosal cingulateDeep brain stimulation of the medial forebrain bundle or subcallosal cingulate | Device | Active followed by sham stimulation, Sham followed by active stimulation |
| Sham stimulationSham stimulation for 2 weeks (Cross-over design) | Device | Active followed by sham stimulation, Sham followed by active stimulation |
Primary outcome
Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively
Time frame: 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
Time frame: 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.
5 secondary outcomes
Mean Hamilton Depression Score (17-item version) at the end of the sham-stimulation compared with at the end of the true-stimulation
Time frame: 6 months
Hamilton Depression score (17-item version) at 12 months
Time frame: 12 months
Montgomery Asberg Depression Depression Rating Scale at 12 months
Time frame: 12 months
Beck Depression Inventory at 12 months
Time frame: 12 months
Short Form (36) Health Survey (SF-36) at 12 months
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anusha Baskaran, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Active stimulation of the medial forebrain bundle or subcallosal cingulate in people with Treatment Resistant Depression, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anusha Baskaran, PhD (Anusha.baskaran@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Qualitative report of any adverse events occurring up until 6 months postoperatively (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.