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Cortical Stimulation to Treat Obsessive Compulsive Disorder

Primary Purpose

Obsessive-Compulsive Disorder

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Standard Therapeutic Deep Brain Stimulation

Cortical Stimulation for PFC

Cortical Stimulation for ACC

About this trial

This is an interventional supportive care trial for Obsessive-Compulsive Disorder focused on measuring OCD, Obsessive Compulsive Disorder, Obsessive thoughts, Compulsions

Eligibility Criteria

22 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ability to give informed consent for the study
Age 22-75
Clinical diagnosis of OCD
Documented duration of OCD of at least 5 years
OCD rated as severe or extreme illness (YBOCs ≥ 28)
Has failed to improve following treatment with at least two selective serotonin reuptake inhibitors (SSRIs), clomipramine, and augmentation with antipsychotics
Has not responded to adequate trials of cognitive behavior therapy (exposure and response prevention)
Has not responded adequately to TMS treatment for OCD if it is reasonably available to the patient

Exclusion Criteria:

Has hoarding as a primary subclassification of OCD according to DSM-4
Has another severe psychiatric disorder (personality disorder, psychotic/bipolar disorder, etc) or substance abuse issues
Is pregnant
Has an abnormal MRI assessed by the team or has a neurological condition requiring an MRI in the future
Has a cognitive disorder or dementia
Is at imminent risk for suicide based upon Suicide Severity Rating Scale (SSRS) or has ever attempted suicide
Inability to comply with study follow-up visits
Major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin)
Allergies or known hypersensitivity to materials in the Activa systems (i.e. titanium, polyurethane, silicone, polyethermide, stainless steel).
Previous cranial ablative or deep brain stimulation surgery.
Patients may be excluded from enrollment due to a condition that, in the judgement of the PI, significantly increases risk or reduces significantly the likelihood of benefit from DBS.

Sites / Locations

UCSF Nancy Friend Pritzker Psychiatry BuildingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Prefrontal Cortex (PFC)

Anterior Cingulate Cortex (ACC)

Arm Description

The Prefrontal Cortex (PFC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the PFC.

The Anterior Cingulate Cortex (ACC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the ACC.

Outcomes

Primary Outcome Measures

Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from 12 months to 24 months

The Y-BOCS is an OCD symptom scale used for identifying current OCD symptom severity. The score ranges from 0-40, with higher scores indicating more severe OCD symptoms. The change in Y-BOCS score from 12 months to 24 months will be reported.

Secondary Outcome Measures

Change in Montgomery Asberg Depression Rating Scale (MADRS) score from 12 months to 24 months

Effect size of cortical stim + ALIC DBS compared to ALIC DBS (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score at 12 months and 24 months. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

Full Information

NCT ID

NCT04958096

First Posted

June 27, 2021

Last Updated

November 21, 2022

Sponsor

Andrew Moses Lee, MD, PhD

1. Study Identification

Unique Protocol Identification Number

NCT04958096

Brief Title

Cortical Stimulation to Treat Obsessive Compulsive Disorder

Official Title

Adjunct Cortical Stimulation With Deep Brain Stimulation (DBS) to Treat Obsessive Compulsive Disorder (OCD)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 1, 2021 (Actual)

Primary Completion Date

August 1, 2026 (Anticipated)

Study Completion Date

August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Andrew Moses Lee, MD, PhD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

5. Study Description

Brief Summary

The purpose of this study is to identify abnormal brain signals associated with Obsessive Compulsive Disorder (OCD) and psychiatric symptoms and to investigate novel therapeutic stimulation sites. While treating OCD with standard deep brain stimulation (DBS) therapy, the investigators will also monitor the activity of the anterior cingulate and prefrontal cortex, a region known be involved with OCD, decision making, and emotion regulation, and the investigators will identify abnormal activity corresponding to the severity of a patient's OCD. The investigators will also investigate whether it is possible for stimulation delivered to these parts of the brain can improve OCD symptoms. These investigations have the potential to aid in the development of improved forms of DBS that can better target abnormal OCD brain signatures in the future. The investigators will implant a cortical electrode in addition to the ALIC DBS electrode and connect these to an implantable pulse generator that care store field potential data (Medtronic Percept). The decision whether the lead is placed in the prefrontal or cingulate cortex bilaterally will be based upon considerations of the surgical risks for a particular patient based upon their anatomy and the required surgical approach. At multiple time points post-implantation up to 2 years, in our clinic or patient's homes, cortical and subcortical signals will be recorded. Data will be collected while patient are resting or engaged in symptom provocation tasks, emotional/cognitive tasks while cortical stimulation is on and off. In addition to brain signal recordings, symptoms will be assessed using validated questionnaires and tasks to allow identification of neurophysiological correlates of OCD symptoms.

Detailed Description

The investigators propose to perform electrophysiological investigations into the corticostriatal circuits mediating severe, refractory obsessive compulsive disorder (OCD) through chronic intracranial recordings and stimulation. This new study will utilize the Medtronic Percept, which is currently is approved for treating OCD under the Humanitarian Device Exemption (HDE). In addition to their standard therapeutic DBS electrode(s) in the standard subcortical targets (anterior limb of the internal capsule- ALIC), patients enrolled in this study will have a second pair of leads placed in either the prefrontal cortex (PFC) or anterior cingulate cortex (ACC) bilaterally as well the surrounding white matter tracts for a total of 4 DBS leads. After electrode implantations, patient will undergo 2 phases: In phase 1 (day 1 - 12 months), the aim will be to identify a biomarker of OCD-related symptoms. Patient will undergo long-term monitoring of their OCD and related psychiatric symptoms along with recordings of cortical and subcortical local field potentials (LFPs). This phase will be conducted in both the outpatient office setting and patient's home environment. In phase 2 (13 months - 2 years), the investigators will introduce cortical stimulation at either the PFC or ACC/cingulum in addition to stimulation at the ALIC. The investigators will continue to obtain brain recordings and ratings during this period of time to identify the impact of cortical stimulation on these signals.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obsessive-Compulsive Disorder

Keywords

OCD, Obsessive Compulsive Disorder, Obsessive thoughts, Compulsions

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Prefrontal Cortex (PFC)

Arm Type

Experimental

Arm Description

The Prefrontal Cortex (PFC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the PFC.

Arm Title

Anterior Cingulate Cortex (ACC)

Arm Type

Experimental

Arm Description

The Anterior Cingulate Cortex (ACC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the ACC.

Intervention Type

Device

Intervention Name(s)

Standard Therapeutic Deep Brain Stimulation

Intervention Description

DBS to the standard subcortical targets (anterior limb of the internal capsule- ALIC) will be used to treat OCD

Intervention Type

Device

Intervention Name(s)

Cortical Stimulation for PFC

Other Intervention Name(s)

PFC Stimulation

Intervention Description

Patients enrolled in this study will have a second pair of leads placed in the prefrontal cortex (PFC) bilaterally as well the surrounding white matter tracts and stimulation will be delivered through these leads to improve OCD symptoms

Intervention Type

Device

Intervention Name(s)

Cortical Stimulation for ACC

Other Intervention Name(s)

OCD Cortical Stimulation

Intervention Description

Patients enrolled in this study will have a second pair of leads placed in the anterior cingulate cortex (ACC) bilaterally as well the surrounding white matter tracts and stimulation will be delivered through these leads to improve OCD symptoms

Primary Outcome Measure Information:

Title

Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from 12 months to 24 months

Description

Time Frame

12-24 months

Secondary Outcome Measure Information:

Title

Change in Montgomery Asberg Depression Rating Scale (MADRS) score from 12 months to 24 months

Description

Time Frame

12-24 months

Other Pre-specified Outcome Measures:

Title

Biomarker identification in Stage 1

Description

The number of patients in whom we can identify a neural biomarker that accounts for a significant amount of variance in OCD symptom severity

Time Frame

1-12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to give informed consent for the study Age 22-75 Clinical diagnosis of OCD Documented duration of OCD of at least 5 years OCD rated as severe or extreme illness (YBOCs ≥ 28) Has failed to improve following treatment with at least two selective serotonin reuptake inhibitors (SSRIs), clomipramine, and augmentation with antipsychotics Has not responded to adequate trials of cognitive behavior therapy (exposure and response prevention) Has not responded adequately to TMS treatment for OCD if it is reasonably available to the patient Exclusion Criteria: Has hoarding as a primary subclassification of OCD according to DSM-4 Has another severe psychiatric disorder (personality disorder, psychotic/bipolar disorder, etc) or substance abuse issues Is pregnant Has an abnormal MRI assessed by the team or has a neurological condition requiring an MRI in the future Has a cognitive disorder or dementia Is at imminent risk for suicide based upon Suicide Severity Rating Scale (SSRS) or has ever attempted suicide Inability to comply with study follow-up visits Major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin) Allergies or known hypersensitivity to materials in the Activa systems (i.e. titanium, polyurethane, silicone, polyethermide, stainless steel). Previous cranial ablative or deep brain stimulation surgery. Patients may be excluded from enrollment due to a condition that, in the judgement of the PI, significantly increases risk or reduces significantly the likelihood of benefit from DBS.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Andrew M Lee, MD, PhD

Phone

415-502-5472

ocdresearch@ucsf.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Tenzin Norbu, BS

Phone

415-514-6489

ocdresearch@ucsf.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew M Lee, MD, PhD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF Nancy Friend Pritzker Psychiatry Building

City

San Francisco

State/Province

California

ZIP/Postal Code

94107

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Andrew M Lee, MD, PhD

Phone

415-502-5472

ocdresearch@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Tenzin Norbu, BS

Phone

415-514-6489

ocdresearch@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Andrew M Lee, MD, PhD

First Name & Middle Initial & Last Name & Degree

Tenzin Norbu, BS

12. IPD Sharing Statement

Plan to Share IPD

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Cortical Stimulation to Treat Obsessive Compulsive Disorder

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