Clinical trial NCT04958096: 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
Overall status: RECRUITING
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: OCD
Obsessive Compulsive Disorder
Obsessive thoughts
Compulsions
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2021-07-12
Enrollment: 15
Sex: ALL
Minimum age (years): 22
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from 12 months to 24 months
timeFrame: 12-24 months
Secondary outcomes:
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS) score from 12 months to 24 months
timeFrame: 12-24 months
Other outcomes:
measure: Biomarker identification in Stage 1
timeFrame: 1-12 months
Locations:
city: San Francisco
country: United States
facility: UCSF Nancy Friend Pritzker Psychiatry Building
state: California
Study officials:
affiliation: University of California, San Francisco
name: Andrew M Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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