Personalized DBS for OCD Guided by Stereoencephalography Mapping

NCT06347978 | Recruiting DMC FDA Device

• 1 other identifier: 24-41296
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obsessive-Compulsive Disorder; OCD

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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

  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

  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.

  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

  Approximately 4 years

Secondary Outcomes (3)

• Secondary Efficacy Endpoint #1 - Improvement in YBOCS scores from Baseline

  Approximately 4 years

• Secondary Efficacy Endpoint #2 - Improvement in OCD Symptoms from Baseline

  Approximately 4 years

• Secondary Efficacy Endpoint #3 - Improvement in Depression Symptoms from Baseline

  Approximately 4 years

Study Arms (2)

ON-OFF (Stimulation-Sham)

EXPERIMENTAL

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: Deep Brain Stimulation

OFF-ON (Sham-Stimulation)

EXPERIMENTAL

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: Deep Brain Stimulation

Interventions

Deep Brain Stimulation DEVICE

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.

OFF-ON (Sham-Stimulation); ON-OFF (Stimulation-Sham)

Eligibility Criteria

• Age: 22 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 22 years and ≤ 75 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 all 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 (PI). Patients may continue to be receiving these following treatments while still enrolled in the study.
• 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)
• Has not responded adequately to TMS treatment for OCD if it is reasonably available to the patient
• 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
• 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

You may not qualify if:

• 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 and brought by study staff to the nearest emergency room for additional evaluation and psychiatric care.
• 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:

Sponsors & Collaborators

• Andrew Moses Lee, MD, PhD: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (3)

• Scangos KW, Makhoul GS, Sugrue LP, Chang EF, Krystal AD. State-dependent responses to intracranial brain stimulation in a patient with depression. Nat Med. 2021 Feb;27(2):229-231. doi: 10.1038/s41591-020-01175-8. Epub 2021 Jan 18.

  PMID: 33462446 BACKGROUND

• Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, du Montcel ST, Yelnik J, Chereau I, Arbus C, Raoul S, Aouizerate B, Damier P, Chabardes S, Czernecki V, Ardouin C, Krebs MO, Bardinet E, Chaynes P, Burbaud P, Cornu P, Derost P, Bougerol T, Bataille B, Mattei V, Dormont D, Devaux B, Verin M, Houeto JL, Pollak P, Benabid AL, Agid Y, Krack P, Millet B, Pelissolo A; STOC Study Group. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008 Nov 13;359(20):2121-34. doi: 10.1056/NEJMoa0708514.

  PMID: 19005196 BACKGROUND

• Denys D, Graat I, Mocking R, de Koning P, Vulink N, Figee M, Ooms P, Mantione M, van den Munckhof P, Schuurman R. Efficacy of Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Refractory Obsessive-Compulsive Disorder: A Clinical Cohort of 70 Patients. Am J Psychiatry. 2020 Mar 1;177(3):265-271. doi: 10.1176/appi.ajp.2019.19060656. Epub 2020 Jan 7.

  PMID: 31906709 BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• A Moses Lee, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Andrew Krystal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tenzin Norbu, BS

CONTACT

415-885-7707; ocdresearch@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 4, 2024
• Study Start: May 24, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)