Magnetic Resonance-Guided Focused Ultrasound Bilateral Capsulotomy for Refractory Anorexia Nervosa With Comorbid Obsessive Compulsive Disorder or Major Depressive Disorder

NCT07113665 | Recruiting Phase 1 DMC

• 1 other identifier: 6590
• 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 clinical effectiveness of MRI-guided focused ultrasound (MRgFUS) thermal ablation (capsulotomy) in patients with treatment-refractory anorexia nervosa (AN) and comorbid obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). The main questions it aims to answer are:

1. 1.Can MR-guided focused ultrasound capsulotomy be safely delivered through an intact skull in patients with treatment-refractory anorexia nervosa and comorbid OCD and/or MDD, with a safety and side-effect profile comparable to traditional radiofrequency neurosurgical approaches?
2. 2.Does MRgFUS capsulotomy produce clinical outcomes comparable to open surgical ablative procedures-specifically, improvements in anxiety, mood, quality of life, anorexia nervosa psychopathology, habit formation, and weight-in patients with treatment-refractory anorexia nervosa?
3. 3.Undergo baseline imaging and clinical assessments
4. 4.Receive a single MRgFUS capsulotomy targeting the ALIC
5. 5.Be monitored for 24 months post-treatment to assess adverse events, quality of life, and symptom changes using standardized clinical and neuropsychiatric measures

Conditions

Anorexia Nervosa (DSM-IV Revised Criteria)

Keywords

Anorexia Nervosa; MR-guided Focused Ultrasound; bilateral capsulotomy; Obsessive Compulsive Disorder; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Safety and Feasibility of MRgFUS Capsulotomy in Patients with Treatment-Refractory Anorexia Nervosa

  The frequency and severity of adverse events associated with ExAblate Transcranial Magnetic Resonance-guided Focused Ultrasound (MRgFUS) will be evaluated in patients with treatment-refractory anorexia nervosa and comorbid obsessive-compulsive disorder (OCD) and/or major depressive disorder (MDD). All adverse events-including procedure-related complications, neurological events, and other safety concerns-will be systematically documented, monitored, and assessed throughout the study duration.

  From day of treatment through 24 months post-treatment with evaluations at immediate post-op, 1, 3, 6, 12, 18 and 24 months.

Secondary Outcomes (6)

• Change in Body Mass Index Following MRgFUS Capsulotomy

  Assessments will be conducted at baseline, 1, 3, 6, 12, 18, and 24 months following the procedure.

• Change in Depressive Symptoms Using the Beck Depression Inventory

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

• Change in Anxiety Symptoms Using the Beck Anxiety Inventory

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

• Change in Quality of Life Using the Quality of Life Enjoyment and Satisfaction Questionnaire

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

• Change in Obsessive-Compulsive Symptoms Using the Obsessive Compulsive Inventory

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

Study Arms (1)

MR- guided Focused Ultrasound Capsulotomy

EXPERIMENTAL

Participants in this arm will undergo a single MRI-guided focused ultrasound (MRgFUS) thermal ablation procedure targeting the anterior limb of the internal capsule (ALIC). The procedure is performed using the ExAblate 4000 MRgFUS system, with real-time MR thermometry to ensure precise lesioning. This intervention is intended for individuals with treatment-refractory anorexia nervosa (AN) and comorbid obsessive-compulsive disorder (OCD) and/or major depressive disorder (MDD) who meet surgical eligibility criteria. All participants will complete standardized psychiatric and quality of life assessments at baseline and follow-up time points up to 24 months post-treatment to evaluate safety, feasibility, and preliminary clinical efficacy.

Device: ExAblate Neuro 4000

Interventions

ExAblate Neuro 4000 DEVICE

The ExAblate Neuro 4000 is an MRI-guided focused ultrasound (MRgFUS) system designed to perform noninvasive thermal ablation of targeted brain tissue. In this study, the ExAblate Neuro 4000 will be used to perform a bilateral capsulotomy by ablating the anterior limb of the internal capsule (ALIC) in patients with treatment-refractory anorexia nervosa (AN) and comorbid obsessive-compulsive disorder (OCD) and/or major depressive disorder (MDD). The procedure will be conducted under real-time MRI guidance and thermometry to ensure accurate targeting and controlled thermal delivery. This study aims to evaluate the safety, feasibility, and preliminary clinical benefit of MRgFUS in improving psychiatric symptoms and quality of life in this patient population.

MR- guided Focused Ultrasound Capsulotomy

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.
• DSM-V diagnosis of Anorexia Nervosa, with co-morbid diagnosis of OCD and/or Major depressive disorder.
• Treatment refractoriness indicated by any of:
• Duration of illness more than 10 years with no more than three months of remission in terms of weight;
• At least three attempts at expert hospital based treatment that were not successful or where there was no sustained response to treatment;
• A pattern of increased medical instability requiring at least two episodes of emergency/involuntary re-feeding and lasting at least two years;
• Ability to provide informed consent/competent to make medical decisions.

You may not qualify if:

• Patients with unstable cardiac status \[e.g. Unstable angina pectoris on medication, Patients with documented myocardial infarction within six months, Congestive heart failure requiring medication (other than diuretic), Patients on anti-arrhythmic drugs, Severe hypertension (diastolic BP \> 100 on medication)\]
• 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 INR)
• Cerebrovascular disease (e.g. CVA 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.
• Patients with brain tumors already known or revealed on pretreatment MRI
• Currently pregnant (as determined by history and serum HCG) or lactating.
• Chemical abuse or dependence within the previous six months
• Presence of a metabolic pathology interfering with eating or digestion (e.g. diabetes).

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Anorexia Nervosa; Obsessive-Compulsive Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Anxiety Disorders; Depressive Disorder; Mood 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: phase 1
• 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: August 6, 2025
• First Posted: August 11, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)