SEEG-Guided DBS for OCD

Study Overview
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Brief Summary
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This is a dual-site, 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 DBS surgery and further optimization of stimulation parameters. Stage 3 will be randomized, crossover treatment, followed by open label treatment.

Official Title
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A Double-Blinded, Randomized, Crossover Trial of Stereoencephalography- Guided Multi-Lead Deep Brain Stimulation for Treatment-Refractory Obsessive- Compulsive Disorder (SEEG-Guided DBS for OCD)

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Device: PMT Stereoencephalography (SEEG)
* Device: Vercise Genus™ Deep Brain Stimulation (DBS) System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 22 years and ≤ 65 years of age, at the time of screening Chronic (> 5 years preceding the date of enrollment) OCD, diagnosed as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition guidelines (DSM-5) Presence of obsessions, compulsions, or both Time-consuming obsessions and compulsions that take more than one hour a day or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning Obsessive-compulsive symptoms that are not attributable to the physiological effects of a substance (e.g. a drug of abuse, a medication) or another medical condition Disturbance not better explained by the symptoms of another mental disorder listed in the DSM-5 Severe OCD symptoms, as defined by Y-BOCS I score of ≥ 28, within two weeks prior to enrollment Lack of adequate response to a history of the following treatments, based on information from any of the following: (a) the current treating physician and/or psychologist; (b) medical records or other forms of communication from previous healthcare providers; and (c) pharmacy records, as determined by the Principal Investigator Adequate trial of ≥ 2 selective serotonin reuptake inhibitors (SSRIs) for an adequate duration at the maximum dose recommended for OCD or at the maximally-tolerated dose according to the FDA-approved package labeling Adequate trial of ≥ 1 augmentation trial using an antipsychotic medication Adequate trial of clomipramine, either as monotherapy or as an augmentation therapy, unless medically contradicted Adequate trials of cognitive behavior therapy-based Exposure and Response Prevention (ERP) Willingness and ability to remain on the same daily dose of any and all scheduled psychotropic medication(s) for at least 8 weeks prior to study enrollment and for the duration of the trial, in the opinion of the Principal Investigator Willingness and ability to discontinue any psychotherapeutic behavioral intervention therapy (e.g. CBT) until the maintenance stage, if determined safe by the research/study psychiatrist Study participation in the prospective subject's best psychiatric interest, as determined by the research/study psychiatrist and based on a comprehensive assessment that includes the following: (a) detailed psychiatric history; (b) examination of the mental status; (c) review of psychiatric assessment measures obtained to determine eligibility, as applicable; (d) review of previous medical records for a minimum of 2 years prior to enrollment, or as applicable; and (e) consideration of the potential benefits versus risks of study participation Agreement to being evaluated by a licensed psychiatrist and/or psychologist at regular intervals, as required by the schedule of events, for the duration of study participation Living within 6 hours of driving distance from study sites and no plan of relocation for at least the duration of the trial (approximately 18-24 months), as reported by the prospective subject or a family member Adequate social support, including but not limited to, stable housing and two family members and/or friends, who are identified as a verifiable emergency contacts Willingness and ability to provide at least two verifiable contacts for emergency purposes and to permit verification of emergency contacts by research staff before all study visits and as needed, at the discretion of the Principal Investigator Ability to understand procedure-related instructions and to complete study assessments in English, in the opinion of the Principal Investigator Willingness and ability to comply with protocol requirements (e.g. procedure visits, treatment schedule, follow-up visit schedule, evaluations, etc.), in the opinion of the Principal Investigator Willingness and ability to provide written agreement to allow any and all forms of communication between the research team and treating clinician(s) Willingness and ability to provide informed consent, in the opinion of the Principal Investigator Exclusion Criteria: Diagnosed, according to the Mini International Neuropsychiatric Interview (MINI), as suffering from any other primary psychiatric diagnosis defined in the DSM-5, including Hoarding Disorder In the opinion of the Principal Investigator and relative to the date of enrollment, (a) current or past diagnosis of, or medical history/records suggestive of, a DSM-5 defined Personality Disorder, considered to be severe; or (b) history of hospitalization because of Borderline Personality Disorder Present clinical secondary diagnosis of any of the following, as defined in the DSM-5 and based on the MINI and the psychiatric evaluation: Bipolar I Disorder or Bipolar II Disorder Anorexia Nervosa, Bulimia Nervosa, or Binge Eating Disorder Psychotic Disorder or Mood Disorder with psychotic features Current suicidal risk, as determined by the research/study psychiatrist using the brief mental status exam and the psychiatric interview (including the Columbia Suicide Severity Rating Scale [C-SSRS]), or significant suicide risk, defined as Hamilton Depression Rating Scale (HDRS-21) Item 3 score of ≥ 3 or any lifetime history of suicide attempt a. Subjects who answer 'Yes' to questions 3, 4, or 5 of the C-SSRS will be excluded. Treatment, within 24 months of screening, for any of the following: dependency on, addiction to, use of, abuse of, or overuse of any illicit substance(s), including alcohol, but not including nicotine or caffeine History of head trauma associated with any of the following: Loss of consciousness for > 5 minutes A residual effect(s) that failed to resolve completely at least 1 year prior to the date of screening An abnormality on a neuroimaging study (MRI, CT Scan) that was/is attributable to the head trauma > 1 head injury within the past 2 years which were diagnosed as a concussion, concussive-type or traumatic brain injury (TBI), according to medical records or as reported by the prospective subject or a family member Any of the following permanent implants: Cardiac implant (e.g. pacemaker or any intracardiac lines, implanted neurostimulators, shunts) Brain implant (e.g. intracranial implant, aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) Implanted medical pumps Diathermy treatments requirement for any reason Hearing loss that, in the opinion of the Principal Investigator, an audiologist, or a treating physician, is likely to affect the subject's ability to comply with all of the requirements of the study or may affect the integrity of the study data Any metal or metallic particles anywhere in the head, except in the inside of the mouth Pregnancy, at the time of screening or during the course of the study (i.e. 3 years) a. Acceptable methods of contraception include the following: i. Established use of oral, injected or implanted contraceptives ii. Placement of an intrauterine device (IUD) or an intrauterine system (IUS) iii. Female sterilization (e.g. surgical bilateral oophorectomy with or without hysterectomy, total hysterectomy, tubal ligation) iv. Male sterilization, with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate v. True abstinence, when in line with the preferred and usual lifestyle of the subject b. Barrier methods of contraception, such as a condom, a diaphragm, or cervical/vault caps with spermicidal foam/gel/film/cream/suppository, and rhythm methods of contraception, although encouraged, alone are not considered acceptable forms or contraception. History of involuntary movements, in the opinion of the Principal Investigator or a neuro-radiologist History of excessive or prolonged bleeding and/or any of the following: INR of > 1.8 Prolonged activated partial thromboplastin time (aPTT) of ≥ 45 sec Platelet count of < 75×100/L Allergy to gadolinium Inability to safely and successfully undergo an MRI or a CT Scan Any past or present medical condition, disease, disorder, or injury that, in the opinion of the Principal Investigator, may reduce or hinder the subject's ability to fully comply with all study requirements for the duration of the study or may impact, compromise, or affect the integrity of the data or the results of the study Current participation in other research that may potentially interfere with DBS study objectives or with the ability to follow the timeline of this study, as determined by the Principal Investigator

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Stage 1: Invasive SEEG Monitoring and Recovery Stage 2: SEEG-guided DBS Implantation and Optimization of DBS Programming Stage 3: Randomized Sham-controlled Crossover Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEEG Guided DBS ON-OFF (Stimulation-Sham)<br>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. | Device: PMT Stereoencephalography (SEEG)<br>* For Stage 1 of this study, we will be implanting depth electrodes to record stereoencephalography across a network of brain regions.<br>Device: Vercise Genus™ Deep Brain Stimulation (DBS) System<br>* For Stages 2 and 3 of this study, we intend to use the DBS system to treat patients with severe symptoms of chronic, treatment-refractory OCD by targeting stimulation to sites that have been determined to have therapeutic benefit during our SEEG Invasive Monitoring phase.<br>|
| Sham Comparator: SEEG Guided DBS OFF-ON (Sham-Stimulation)<br>Patients in the OFF-ON will have their devices turned off and will not have their device switched on (activated) until the crossover point. | Device: PMT Stereoencephalography (SEEG)<br>* For Stage 1 of this study, we will be implanting depth electrodes to record stereoencephalography across a network of brain regions.<br>Device: Vercise Genus™ Deep Brain Stimulation (DBS) System<br>* For Stages 2 and 3 of this study, we intend to use the DBS system to treat patients with severe symptoms of chronic, treatment-refractory OCD by targeting stimulation to sites that have been determined to have therapeutic benefit during our SEEG Invasive Monitoring phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Feasibility Endpoint #1 - OCD Relevant Network | Percentage of patients in which an OCD relevant network can be identified during SEEG Stage 1 | 14 days | 
| Primary Feasibility Endpoint #2 - Stimulation Target That Acutely Improves OCD Symptoms | Percentage of patients in which we can identify a stimulation target that acutely improves OCD symptoms during SEEG Stage 1 | 14 days | 
| Primary Feasibility Endpoint #3 - Willingness to Continue with DBS Stage 2 | Percentage of patients willing and able to continue with the DBS Stage 2 after completing the SEEG Stage 1 | Day 14 | 
| Primary Feasibility Endpoint #4 - Acute Symptomatic Improvement | Percentage of implanted DBS sites associated with both acute symptomatic improvement during the SEEG Stage 1 and therapeutic benefit during the DBS Stage 2. | Approximately 60 weeks | 
| Primary Efficacy Endpoint - Treatment Response | Treatment response, determined by the difference in Y-BOCS II score between the active stimulation (ON) condition and sham control (OFF) condition | Up to 24 weeks | 
| 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. | Approximately 4 years |