Treatment-Resistant DepressionNCT07108257
Magnetic Resonance-Guided Focused Ultrasound Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression
A study testing ExAblate Neuro 4000 in people with Treatment-Resistant Depression and Bipolar Depression, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment-Resistant Depression, Bipolar Depression
- What is being tested?
- ExAblate Neuro 4000
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 25 Jun 2025to 16 Jul 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥18 and ≤65 years of age, inclusive.
- Patients who are competent and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Bipolar Disorder, Type 1 or Type 2.
- A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (at least 2 weeks of major depression at the time the HAMD is conducted).
- Treatment refractory bipolar depression indicated by at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. The minimum duration for being on either of these regimens should be 4 weeks.
- Ability to provide informed consent/competent to make medical decisions.
Who cannot join
- Patients with unstable cardiac status [e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP > 100 on medication)] 2. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- 3. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal International Normalized Ratio) 4. Cerebrovascular disease (e.g. Cerebrovascular Accident within 6 months) or history of intracranial hemorrhage.
- 5. Untreated, uncontrolled sleep apnea. 6. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure.
- 7. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
- 8. Are participating or have participated in another clinical trial in the last 30 days.
- 9. Patients unable to communicate with the investigator and staff. 10. Presence of significant cognitive impairment 11. History of psychosis on clinical evaluation. 12. Catatonic or psychotic or actively suicidal on clinical evaluation. 12. Patients with brain tumors already known or revealed on pretreatment MRI. 13. Currently pregnant (as determined by history and serum Human Chorionic Gonadotropin) or lactating.
- 14. Chemical abuse or dependence within the previous six months
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario
About this study
Official title: Phase I Trial of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression
The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD).
Read the detailed description
This study is a prospective, single arm and nonrandomized phase l study.
Participants will:
- Undergo MRgFUS capsulotomy targeting the anterior limb of the internal capsule.
- Be assessed before and after treatment for adverse events, symptom changes, and quality of life.
- Complete a battery of clinical rating scales including the Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Young Mania Rating Scale (YMRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Columbia-Suicide Severity Rating Scale (C-SSRS), along with the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ).
A total of 10 participants, all patients at Sunnybrook Hospital, are expected to enroll in the study. Each participant will be involved for approximately 26 months, including a 2-month pre-treatment period and 24 months of follow-up. The full study duration is estimated at 3 years, with primary results anticipated within 2 to 3 years.
- Conditions
- Treatment-Resistant Depression, Bipolar Depression
- Being tested
- ExAblate Neuro 4000
- Keywords
- TRBD, FUS, MRgFUS, capsulotomy, Focused Ultrasound, MR-guided Focused Ultrasound, refractory Bipolar Depression
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExAblate Neuro 4000Device
ExAblate Neuro 4000 is an MR-guided focused ultrasound (MRgFUS) device used to perform noninvasive thermal ablation of targeted brain tissue. In this study, ExAblate Neuro 4000 will be used to ablate the anterior limb of the internal capsule (capsulotomy) in patients with treatment-resistant bipolar depression (TRBD). The procedure is conducted under real-time MRI guidance and thermometry to assess safety and initial effectiveness in improving clinical symptoms and quality of life.
| Study group | Role | What they receive |
|---|---|---|
| MR-guided Focused Ultrasound Capsulotomy in Treatment-Resistant Bipolar Depression | Experimental | Participants in this arm will undergo MR-guided focused ultrasound (MRgFUS) capsulotomy targeting the anterior limb of the internal capsule. The procedure is intended to thermally ablate this brain region to assess safety and initial effectiveness in reducing symptoms of treatment-resistant bipolar depression (TRBD). All participants will receive the same intervention and will be followed for 24 months post-treatment to evaluate clinical outcomes, adverse events, and quality of life. Receives: Device: ExAblate Neuro 4000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Magnetic Resonance-guided Focused Ultrasound for patients with Treatment-Resistant Bipolar Disorder
Assessment of the frequency and severity of adverse events associated with ExAblate Transcranial Magnetic Resonance-guided Focused Ultrasound (MRgFUS) in patients with Treatment-Resistant Bipolar Disorder (TRBD). Adverse events, including procedure-related complications and neurological events, will be documented and assessed.
Measured: From the treatment day visit through the 24-month post-treatment time points.
Secondary outcomes (6)
Clinical Efficacy - Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (HAMD-17)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing symptoms of bipolar depression. Clinical efficacy will be assessed by the change in scores on the Hamilton Depression Rating Scale - 17 item version (HAMD-17) from baseline through follow-up visits. The HAMD-17 is a clinician-administered scale that assesses the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating more severe depression.
Measured: Assessed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months post-treatment.
Change in Depressive Symptom Severity Measured by the Beck Depression Inventory (BDI)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing depressive symptom severity using the Beck Depression Inventory, a validated patient-reported scale. Assessments will occur at baseline and at specified follow-up visits. The BDI consists of 21 items assessing symptoms of depression experienced over the past two weeks. Total scores range from 0 to 63, with higher scores indicating more severe depressive symptoms.
Measured: Assessed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months post-treatment.
Clinical Efficacy - Change in Anxiety Symptoms measured by Beck Anxiety Inventory (BAI)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing anxiety symptom severity using the Beck Anxiety Inventory (BAI), a validated patient-reported scale. Assessments will occur at baseline and at specified follow-up visits. The BAI consists of 21 items measuring common symptoms of anxiety experienced over the past week. Each item is rated on a scale from 0 (not at all) to 3 (severely). Total scores range from 0 to 63, with higher scores indicating more severe anxiety symptoms.
Measured: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Clinical Efficacy - Change in Manic Symptoms measured by Young Mania Rating Scale (YMRS)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing manic symptom severity using the Young Mania Rating Scale (YMRS), a validated clinician-administered rating scale. Assessments will occur at baseline and at specified follow-up visits. The YMRS consists of 11 items used to assess the severity of manic symptoms. Total scores range from 0 to 60, with higher scores indicating more severe mania.
Measured: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Clinical Efficacy - Change in Obsessive-Compulsive Symptoms measured by Yale-Brown Obsessive Compulsive Scale (YBOCS)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing obsessive-compulsive symptom severity using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Assessments will occur at baseline and at specified follow-up visits. The Y-BOCS is a clinician-administered instrument that assesses the severity of obsessive and compulsive symptoms. Total scores range from 0 to 40, with higher scores indicating more severe obsessive-compulsive symptoms.
Measured: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment
Change in Suicidal Ideation and Behavior measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
Evaluate the effectiveness of MR-guided Focused Ultrasound (MRgFUS) in reducing suicidal ideation and behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS). Assessments will occur at baseline and at specified follow-up visits. The C-SSRS is a clinician-administered tool that categorizes the severity and intensity of suicidal ideation and records the presence or absence of suicidal behavior. Suicidal ideation is rated on a scale from 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is assessed based on the occurrence of actual, aborted, or interrupted suicide attempts, and preparatory behaviors. Higher scores or presence of behaviors indicate greater severity.
Measured: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2025
- Study start25 Jun 2025
- Primary completion16 Sep 2027 (estimated)
- Study completion16 Jul 2028 (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.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- 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
- NCT07108257
- Sponsor's protocol ID
- 6670
- Status last verified
- Jun 2025
- First submitted
- 20 Jun 2025
- Last updated
- 6 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression
- ClinicalTrials.gov ID
- NCT07108257
- Acronym / sponsor ID
- 6670
- Conditions
- Treatment-Resistant Depression, Bipolar Depression
- Keywords
- TRBD, FUS, MRgFUS, capsulotomy, Focused Ultrasound, MR-guided Focused Ultrasound, refractory Bipolar Depression
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 25 Jun 2025 (actual)
- Primary completion
- 16 Sep 2027 (estimated)
- Study completion
- 16 Jul 2028 (estimated)
- First posted
- 6 Aug 2025 (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.
The goal of this clinical trial is to evaluate the safety and initial effectiveness of MR-guided focused ultrasound (MRgFUS) bilateral capsulotomy in patients with treatment-resistant bipolar depression (TRBD).
Detailed description
This study is a prospective, single arm and nonrandomized phase l study.
Participants will:
- Undergo MRgFUS capsulotomy targeting the anterior limb of the internal capsule.
- Be assessed before and after treatment for adverse events, symptom changes, and quality of life.
- Complete a battery of clinical rating scales including the Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Young Mania Rating Scale (YMRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Columbia-Suicide Severity Rating Scale (C-SSRS), along with the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ).
A total of 10 participants, all patients at Sunnybrook Hospital, are expected to enroll in the study. Each participant will be involved for approximately 26 months, including a 2-month pre-treatment period and 24 months of follow-up. The full study duration is estimated at 3 years, with primary results anticipated within 2 to 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MR-guided Focused Ultrasound Capsulotomy in Treatment-Resistant Bipolar Depression | Experimental | Device: ExAblate Neuro 4000Participants in this arm will undergo MR-guided focused ultrasound (MRgFUS) capsulotomy targeting the anterior limb of the internal capsule. The procedure is intended to thermally ablate this brain region to assess safety and initial effectiveness in reducing symptoms of treatment-resistant bipolar depression (TRBD). All participants will receive the same intervention and will be followed for 24 months post-treatment to evaluate clinical outcomes, adverse events, and quality of life. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women ≥18 and ≤65 years of age, inclusive.
- Patients who are competent and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.
- Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of Bipolar Disorder, Type 1 or Type 2.
- A minimum score of 20 on the Hamilton Depression Rating Scale (HAMD) when depressed (at least 2 weeks of major depression at the time the HAMD is conducted).
- Treatment refractory bipolar depression indicated by at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. The minimum duration for being on either of these regimens should be 4 weeks.
Key exclusion criteria (7 listed)
- Patients with unstable cardiac status [e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP > 100 on medication)] 2. Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
- 3. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy, including risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter or abnormal International Normalized Ratio) 4. Cerebrovascular disease (e.g. Cerebrovascular Accident within 6 months) or history of intracranial hemorrhage.
- 5. Untreated, uncontrolled sleep apnea. 6. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure.
- 7. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
- 8. Are participating or have participated in another clinical trial in the last 30 days.
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 |
|---|---|---|
| ExAblate Neuro 4000ExAblate Neuro 4000 is an MR-guided focused ultrasound (MRgFUS) device used to perform noninvasive thermal ablation of targeted brain tissue. In this study, ExAblate Neuro 4000 will be used to ablate the anterior limb of the internal capsule (capsulotomy) in patients with treatment-resistant bipolar depression (TRBD). The procedure is conducted under real-time MRI guidance and thermometry to assess safety and initial effectiveness in improving clinical symptoms and quality of life. | Device | MR-guided Focused Ultrasound Capsulotomy in Treatment-Resistant Bipolar Depression |
Primary outcome
Safety of Magnetic Resonance-guided Focused Ultrasound for patients with Treatment-Resistant Bipolar Disorder
Time frame: From the treatment day visit through the 24-month post-treatment time points.
Assessment of the frequency and severity of adverse events associated with ExAblate Transcranial Magnetic Resonance-guided Focused Ultrasound (MRgFUS) in patients with Treatment-Resistant Bipolar Disorder (TRBD). Adverse events, including procedure-related complications and neurological events, will be documented and assessed.
6 secondary outcomes
Clinical Efficacy - Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (HAMD-17)
Time frame: Assessed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months post-treatment.
Change in Depressive Symptom Severity Measured by the Beck Depression Inventory (BDI)
Time frame: Assessed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months post-treatment.
Clinical Efficacy - Change in Anxiety Symptoms measured by Beck Anxiety Inventory (BAI)
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Clinical Efficacy - Change in Manic Symptoms measured by Young Mania Rating Scale (YMRS)
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Clinical Efficacy - Change in Obsessive-Compulsive Symptoms measured by Yale-Brown Obsessive Compulsive Scale (YBOCS)
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment
Change in Suicidal Ideation and Behavior measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ExAblate Neuro 4000 in people with Treatment-Resistant Depression and Bipolar 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 6 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 6 Aug 2025. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nir Lipsman, MD, PhD, FRCSC ((416)-480-6954, Nir.Lipsman@sunnybrook.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Magnetic Resonance-guided Focused Ultrasound for patients with Treatment-Resistant Bipolar Disorder (time frame: From the treatment day visit through the 24-month post-treatment time points.). 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 6 Aug 2025.