Phase I trial of mr-guided focused ultrasound for refractory obsessive-compulsive disorder: Clinical and imaging correlates

Karim Mithani 1, 2 ; Anusha Baskaran 1, 2 ; Ying Meng 1, 2, 3 ; Nir Lipsman 1, 2, 3

1. Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 2. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada;  3. Institute of Medical Sciences, University of Toronto, Toronto, Canada

Obsessive-compulsive disorder (OCD) is amongst the most common, challenging, and debilitating anxiety disorders. A large proportion of OCD patients remain symptomatic despite optimized medical and psychotherapeutic care, and may therefore require surgical treatment. Current neurosurgical approaches, however, require cranial access, with attendant risk of brain injury and infection. MR-guided Focused Ultrasound (MRgFUS) is a novel, non-invasive approach to lesioning deep brain targets, which obviates the need for open neurosurgery. A prospective, single-arm, non-randomized, Phase I, pilot trial for safety and feasibility was initiated. Thus far, 3 OCD patients who were deemed treatment-refractory by multiple psychiatrists have been enrolled. Treatments were administered by a neurosurgeon, and supported by anesthesiologists, physicists, psychiatrists, and nurses. Patients have been, and will be, followed-up at 7 days, 1 month, 3 months, 6 months, and 12 months after the procedure. These visits involve evaluation of general health, neurological changes, as well as device-/procedure-related adverse events. Various PET and MR imaging are also being performed, as per a pre-defined schedule. Adverse events are being recorded and categorized by severity, and efficacy is being evaluated using various psychiatric scales, including the Yale-Brown Obsessive Compulsive Scale (YBOCS). Preliminary analyses demonstrate a YBOCS reduction in all three patients 1-month post-operatively (mean reduction = 5, 95% CI = -5.83-15.83). Although these results are not statistically significant, previous studies have repeatedly demonstrated a significant time-delay (frequently >1 year) between psychosurgical operations and meaningful symptom improvement. Since this is a pilot, phase I study, there is no statistical analysis proposed; safety and efficacy assessments will be descriptive, with no statistical endpoint. This is an ongoing clinical trial (ClinicalTrials.gov #NCT03156335), and results will be updated as the study progresses.