Phase I Trial of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Safety of Magnetic Resonance-guided Focused Ultrasound for patients with Treatment-Resistant Bipolar Disorder
Study Overview
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).
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
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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)]
- •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)
- •Cerebrovascular disease (e.g. Cerebrovascular Accident within 6 months) or history of intracranial hemorrhage.
- •Untreated, uncontrolled sleep apnea.
- •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.
- •Presence of significant cognitive impairment
- •History of psychosis on clinical evaluation.
- •Catatonic or psychotic or actively suicidal on clinical evaluation.
- •Patients with brain tumors already known or revealed on pretreatment MRI.
- •Currently pregnant (as determined by history and serum Human Chorionic Gonadotropin) or lactating.
- •Chemical abuse or dependence within the previous six months
Arms & Interventions
MR-guided Focused Ultrasound Capsulotomy in Treatment-Resistant Bipolar Depression
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.
Intervention: ExAblate Neuro 4000 (Device)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Change in Suicidal Ideation and Behavior measured by Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post-treatment.)
- 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)
Investigators
Dr. Nir Lipsman
Principal Investigator
Sunnybrook Health Sciences Centre