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

Official title

Phase I Trial of Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Bipolar Depression

Overview

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.

Interventions

• Device ExAblate Neuro 4000
  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.

Primary outcome measures

• 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.]

Secondary outcome measures (6)

• 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.]

Eligibility criteria

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 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.

Exclusion criteria

Patients with unstable cardiac status \[e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP > 100 on medication)\] 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre — Toronto

Identifiers

NCT: NCT07108257 · 6670

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗