SEEG-Guided DBS for OCD

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.

Inclusion Criteria:≥ 22 years and ≤ 65 years of age, at the time of screeningChronic (> 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 bothTime-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 functioningObsessive-compulsive symptoms that are not attributable to the physiological effects of a substance (e.g. a drug of abuse, a medication) or another medical conditionDisturbance not better explained by the symptoms of another mental disorder listed in the DSM-5Severe OCD symptoms, as defined by Y-BOCS I score of ≥ 28, within two weeks prior to enrollmentLack 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 InvestigatorAdequate 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 labelingAdequate trial of ≥ 1 augmentation trial using an antipsychotic medicationAdequate trial of clomipramine, either as monotherapy or as an augmentation therapy, unless medically contradictedAdequate 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 InvestigatorWillingness and ability to discontinue any psychotherapeutic behavioral intervention therapy (e.g. CBT) until the maintenance stage, if determined safe by the research/study psychiatristStudy 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 participationAgreement 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 participationLiving 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 memberAdequate social support, including but not limited to, stable housing and two family members and/or friends, who are identified as a verifiable emergency contactsWillingness 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 InvestigatorAbility to understand procedure-related instructions and to complete study assessments in English, in the opinion of the Principal InvestigatorWillingness 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 InvestigatorWillingness 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 InvestigatorExclusion 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 DisorderIn 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 DisorderPresent 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 DisorderAnorexia Nervosa, Bulimia Nervosa, or Binge Eating DisorderPsychotic Disorder or Mood Disorder with psychotic featuresCurrent 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 attempta. 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 caffeineHistory of head trauma associated with any of the following:Loss of consciousness for > 5 minutesA residual effect(s) that failed to resolve completely at least 1 year prior to the date of screeningAn 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 memberAny 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 pumpsDiathermy treatments requirement for any reasonHearing 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 dataAny metal or metallic particles anywhere in the head, except in the inside of the mouthPregnancy, 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-radiologistHistory of excessive or prolonged bleeding and/or any of the following:INR of > 1.8Prolonged activated partial thromboplastin time (aPTT) of ≥ 45 secPlatelet count of < 75×100/LAllergy to gadoliniumInability to safely and successfully undergo an MRI or a CT ScanAny 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 studyCurrent 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