Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Obsessive-compulsive Disorder (OCD)

Phase I Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Obsessive-compulsive Disorder (OCD)

The proposed study is to evaluate the safety and initial efficacy of MRgFUS for patients with treatment-refractory OCD. This study is designed as a prospective, single arm, nonrandomized study. Assessments will be made before and after MRgFUS for adverse events related to treatment, for clinical symptom relief, and quality of life (QoL). The target in the brain chosen for ablation will be the anterior limb of the internal capsule (ALIC) (i.e 'capsulotomy'). Safety will be assessed prospectively in radiologic and clinical terms. Post-procedural imaging will be evaluated for evidence of swelling, hemorrhage, and the evolution of the lesion in the anterior limb of the internal capsule. Patients will be clinically followed up at Day 1, Month 1, Month 3, Month 6 and Month 12 post-procedure. At every follow-up visit, patients will be evaluated for general health, neurological changes, as well as for device/procedure related adverse events. Imaging will also be performed with positron emission tomography (PET) and MRI, as per the Month 3 and Month 12 post-procedure. Feasibility will be evaluated by determining the rate of patient accrual, the tolerability of the procedure for patients, and the technical ability of heating the ALIC to lesional temperatures.

Study Overview

• Status: Completed
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Device: Focused Ultrasound

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothill Medical Centre
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women ≥20 and ≤80 years of age.
2. Patients who are able and willing to give consent and able to attend study visits, as determined by both study Psychiatrist and the surgeon.
3. Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnosis of Obsessive Compulsive Disorder (OCD), at least 5-year illness history with a minimum score of 28 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

4. Medication-refractoriness as determined by an adequate dose and duration of standard psychiatric treatments (including psychotherapy and/or pharmacology) as determined by two psychiatrists associated with the study. Including specifically:

   1. Failed adequate trial of three or more medications accepted as first line in the treatment of OCD
   2. Attempted augmentation, if tolerated, by at least 2 medications known to be first line treatments for OCD
   3. An adequate trial of cognitive behavioural therapy, delivered by a therapist experienced in treating OCD
5. Able to communicate sensations during the ExAblate MRgFUS treatment
6. A consistent dose of all medications in the 30 days prior to study entry.

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. Known intolerance or allergies to MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease
4. Severely impaired renal function (estimated glomerular filtration rate < 30ml/min/1.73 m2) or receiving dialysis
5. 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)
6. Cerebrovascular disease (e.g. cerebrovascular accident within 6 months) or history of intracranial hemorrhage
7. Untreated, uncontrolled sleep apnea
8. 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
9. Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment
10. Are participating or have participated in another clinical trial in the last 30 days
11. Patients unable to communicate with the investigator and staff.
12. Presence of significant cognitive impairment
13. Presence of psychosis on clinical evaluation.
14. Patients with brain tumors already known or revealed on pretreatment MRI
15. Currently pregnant (as determined by history and serum HCG) or lactating.
16. Chemical abuse or dependence within the previous six months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Focused Ultrasound

Device: Focused Ultrasound; MR-guided Focused Ultrasound (MRgFUS) offers the possibility of lesioning deep brain targets, while obviating the need for open surgical approaches. There is no radiation, incision, or burr hole, and lesions are generated in real-time under MR image guidance. Intracranial FUS for other applications, essential tremor most notably, has been shown to be safe and effective, recently receiving Health Canada approval for this indication. The technology, methods and procedures used in this study are identical to those in essential tremor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety]	Adverse events (AE) will be recorded and categorized according to severity and relationship to procedure	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically meaningful reduction in symptoms [Efficacy]	Primary effectiveness will be evaluated using validated scores and subscales related to the symptom being treated (i.e., Yale-Brown Obsessive Compulsive Scale). Efficacy is defined as a clinically meaningful reduction in symptoms at 12 months post-treatment. A patient with OCD is considered to have a treatment response if their YBOCS is reduced by 35% compared to baseline.	12 months

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Hotchkiss Brain Institute, University of Calgary
• Investigators: Principal Investigator: Nir Lipsman, MD, PhD, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute; Principal Investigator: Zelm Kiss, MD, PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2017
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): October 20, 2021

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
• Other Study ID Numbers: 002-2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No