This is a double-blinded, randomized, crossover study design for SEEG-guided 4-lead DBS for treatment-refractory OCD, followed by open label stimulation for an additional 6 months. The study will be conducted in 3 stages: Stage 1 will consist of SEEG brain mapping and optimization of stimulation parameters. Stage 2 will consist of 4-lead DBS surgery with bilateral IPGs and further optimization of stimulation parameters. Stage 3 will be randomized, crossover treatment, followed by open label treatment.
The study consists of 3 stages. In Stage 1, the investigators will implant SEEG depth electrodes into various components of the CSTC OCD circuit such as the OFC, ACC, VC/VS, BNST, and amSTN. The investigators will perform extensive stimulation mapping to identify anatomical sites and stimulation parameters that improve symptoms. The investigators also intend to record abnormal local field potential (LFP) activity during periods of varying intensities of spontaneous and provoked OCD symptom severity and will determine if therapeutic stimulation can normalize abnormal neural activity associated with OCD symptoms. In Stage 2, the investigators will use the information obtained during the SEEG Invasive Monitoring phase (Stage 1) to inform the placement of 4 DBS leads using the Medtronic Percept Implantable Pulse Generator system. DBS leads will be targeted to regions identified, in Stage 1, as being associated with symptomatic improvement and OCD-related neural activity. During this phase, the investigators will perform DBS programming to systematically change stimulation parameters to find parameters that optimally relieve patients' OCD symptoms. In Stage 3, the investigators will then carry out a randomized, controlled, crossover trial to assess the safety, feasibility, and initial efficacy of our SEEG-guided DBS approach for treatment-refractory OCD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
Subjects will be randomized to either ON-OFF (Stimulation-Sham) or OFF-ON (Sham-Stimulation) arms. Patients in the ON-OFF arm will first be treated for up to 12 weeks with the parameters identified during the DBS optimization phase until the washout period. Patients in the OFF-ON will have their devices turned off and will not have their device switched on (activated) until the crossover point. After completion of the first phase of the trial, patients will undergo another washout phase until they are within 20% of their pre-treatment Y-BOCS II score or 4 weeks have passed, whichever comes first. The purpose of the washout is to eliminate any residual effect of stimulation in the ON group. Patients will then be advanced to the crossover phase. The participants who were initially randomized to the ON-OFF arm will be moved onto the sham (OFF) period, and the participants who were initially randomized to the OFF-ON group will be moved onto stimulation (ON) period for up to 12 weeks.
University of California, San Francisco
San Francisco, California, United States
Primary Feasibility Endpoint #1 - Stimulation Target That Acutely Improves OCD Symptoms
Percentage of patients in which the investigators can identify a stimulation target that acutely improves OCD symptoms during the SEEG Stage 1
Time frame: 12 days
Primary Feasibility Endpoint #2 - Identifying an electrophysiological biomarker of OCD
Percentage of patients in which an electrophysiological biomarker of OCD can be identified during the SEEG Stage 1
Time frame: 12 days
Primary Feasibility Endpoint #3 - Acute Symptomatic Improvement
Percentage of implanted DBS sites associated with acute symptomatic improvement during the SEEG Stage 1 that also have long-term therapeutic benefit during the DBS Stage 2
Time frame: 18 months
Primary Feasibility Endpoint #4 - Completion of Stages 1 and 2
Percentage of enrolled patients completing SEEG Stage 1 and Stage 2 of the trial
Time frame: 18 months
Primary Safety Endpoint - Serious Adverse Events
Number and type of serious adverse events in this SEEG-guided 4-lead DBS approach compared to conventional DBS for OCD.
Time frame: Approximately 4 years
Primary Efficacy Endpoint - Treatment Response
Treatment response, determined by the difference in Yale-Brown Obsessive Compulsive Scale (YBOCS) II score between the active stimulation (ON) condition and sham control (OFF) condition
Time frame: Approximately 4 years
Secondary Efficacy Endpoint #1 - Improvement in YBOCS scores from Baseline
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Responder rates, based on ≥ 35% reduction of baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) I and II scores
Time frame: Approximately 4 years
Secondary Efficacy Endpoint #2 - Improvement in OCD Symptoms from Baseline
Reduction of baseline Obsessive-Compulsive Inventory (OCI) score
Time frame: Approximately 4 years
Secondary Efficacy Endpoint #3 - Improvement in Depression Symptoms from Baseline
Reduction of baseline Montgomery and Asberg Depression Rating Scale Self Report (MADRS-SR) score
Time frame: Approximately 4 years