Magnetic Resonance-Guided Focused Ultrasound Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression

NCT07108257 | Recruiting

• 1 other identifier: 6670
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Treatment-Resistant Depression; Bipolar Depression

Keywords

TRBD; FUS; MRgFUS; capsulotomy; Focused Ultrasound; MR-guided Focused Ultrasound; refractory Bipolar Depression

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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)

  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)

  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)

  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)

  Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment

Study Arms (1)

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.

Device: ExAblate Neuro 4000

Interventions

ExAblate Neuro 4000 DEVICE

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.

MR-guided Focused Ultrasound Capsulotomy in Treatment-Resistant Bipolar Depression

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \. 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.
• \. 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.
• \. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
• \. Are participating or have participated in another clinical trial in the last 30 days.
• \. 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.
• \. Chemical abuse or dependence within the previous six months

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Bipolar Disorder

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Central Study Contacts

Nir Lipsman, MD, PhD, FRCSC

CONTACT

(416)-480-6954; Nir.Lipsman@sunnybrook.ca

Anusha Baskaran, PhD

CONTACT

416-480-6100; anusha.baskaran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: August 6, 2025
• Study Start: June 25, 2025
• Primary Completion (Estimated): September 16, 2027
• Study Completion (Estimated): July 16, 2028
• Last Updated: August 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)