Clinical trial NCT03156335: Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Obsessive-compulsive Disorder (OCD)
Official title: Phase I Trial of MR-guided Focused Ultrasound (MRgFUS) Bilateral Capsulotomy for the Treatment of Refractory Obsessive-compulsive Disorder (OCD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Hotchkiss Brain Institute, University of Calgary
First posted: 2017-05-17
Enrollment: 12
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
timeFrame: 12 months
Secondary outcomes:
measure: Clinically meaningful reduction in symptoms [Efficacy]
timeFrame: 12 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothill Medical Centre
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre, Sunnybrook Research Institute
name: Nir Lipsman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Zelm Kiss, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: