Cortical Stimulation to Treat Obsessive Compulsive Disorder

Study Overview
=================
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.

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

Conditions
-----------------
Obsessive-Compulsive Disorder

Intervention / Treatment
-----------------
* Device: Standard Therapeutic Deep Brain Stimulation
* Device: Cortical Stimulation for PFC
* Device: Cortical Stimulation for ACC


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prefrontal Cortex (PFC)<br>The Prefrontal Cortex (PFC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the PFC. | Device: Standard Therapeutic Deep Brain Stimulation<br>* DBS to the standard subcortical targets (anterior limb of the internal capsule- ALIC) will be used to treat OCD<br>Device: Cortical Stimulation for PFC<br>* 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<br>* Other names: PFC Stimulation;|
| Experimental: Anterior Cingulate Cortex (ACC)<br>The Anterior Cingulate Cortex (ACC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the ACC. | Device: Standard Therapeutic Deep Brain Stimulation<br>* DBS to the standard subcortical targets (anterior limb of the internal capsule- ALIC) will be used to treat OCD<br>Device: Cortical Stimulation for ACC<br>* 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<br>* Other names: OCD Cortical Stimulation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12-24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12-24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
OCD, Obsessive Compulsive Disorder, Obsessive thoughts, Compulsions