MRI-guided focused ultrasound capsulotomy for severe, treatment-resistant anorexia nervosa with OCD or depression

Phase I Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Anorexia Nervosa With Co-morbid Obsessive Compulsive Disorder or Major Depressive Disorder

This trial will test whether MRI-guided focused ultrasound capsulotomy can be safely used to help adults with long-standing, treatment-resistant anorexia nervosa who also have obsessive-compulsive disorder or major depression.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07113665 on ClinicalTrials.gov

What this trial studies

This single-centre, single-arm Phase I study will test the safety and initial clinical effects of MR-guided focused ultrasound (MRgFUS) capsulotomy targeting the anterior limb of the internal capsule in ten adults with treatment-refractory anorexia nervosa and comorbid OCD and/or MDD. Each participant will receive a single procedure using the ExAblate Neuro 4000 under continuous MRI guidance and thermometry after comprehensive psychiatric, nutritional, and imaging evaluations. Patients will be followed closely with scheduled visits immediately post-treatment and at 1, 3, 6, 12, 18, and 24 months to monitor safety and changes in anxiety, mood, eating-disorder symptoms, habit formation, and weight. The trial is designed to inform feasibility and whether larger, controlled studies are warranted.

Who should consider this trial

Good fit: Adults 18–65 years with DSM‑V anorexia nervosa who have long-standing, treatment-refractory illness and comorbid OCD and/or major depressive disorder, are competent to consent, and can attend all study visits are the intended candidates.

Not a fit: Patients who are medically unstable, have not undergone adequate prior expert hospital-based treatments, lack the specified comorbidities, or have skull, cardiac, or other conditions that preclude safe MRgFUS delivery are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the minimally invasive MRgFUS capsulotomy could reduce obsessive-compulsive and depressive symptoms, improve eating-disorder psychopathology and weight, and offer an alternative to open surgical ablation for people with treatment-refractory anorexia nervosa.

How similar studies have performed: Ablative capsulotomy and other neurosurgical approaches have shown benefit in severe, treatment-resistant OCD and depression and small MRgFUS psychiatric studies exist, but applying MRgFUS capsulotomy specifically to anorexia nervosa is largely novel.

Eligibility criteria

Inclusion Criteria:

1. Men and women ≥18 and ≤65 years of age, inclusive.
2. Patients who are competent and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.
3. DSM-V diagnosis of Anorexia Nervosa, with co-morbid diagnosis of OCD and/or Major depressive disorder.
4. Treatment refractoriness indicated by any of:

   1. Duration of illness more than 10 years with no more than three months of remission in terms of weight;
   2. At least three attempts at expert hospital based treatment that were not successful or where there was no sustained response to treatment;
   3. A pattern of increased medical instability requiring at least two episodes of emergency/involuntary re-feeding and lasting at least two years;
5. Ability to provide informed consent/competent to make medical decisions.

Exclusion Criteria:

1. 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 INR)
4. Cerebrovascular disease (e.g. CVA 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. Patients with brain tumors already known or revealed on pretreatment MRI
13. Currently pregnant (as determined by history and serum HCG) or lactating.
14. Chemical abuse or dependence within the previous six months
15. Presence of a metabolic pathology interfering with eating or digestion (e.g. diabetes).
16. Body mass index (BMI) less than 13

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Nir Lipsman, MD, PhD, FRCSC

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