Cortical Stimulation to Treat Obsessive Compulsive Disorder

Official title

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

Overview

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.

Interventions

• Device Standard Therapeutic Deep Brain Stimulation
  DBS to the standard subcortical targets (anterior limb of the internal capsule- ALIC) will be used to treat OCD
• Device Cortical Stimulation for PFC
  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
• Device Cortical Stimulation for ACC
  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 measures

• Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) from 12 months to 24 months [Time frame: 12-24 months]

Secondary outcome measures (1)

• Change in Montgomery Asberg Depression Rating Scale (MADRS) score from 12 months to 24 months [Time frame: 12-24 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

United States · 1 center

• UCSF Nancy Friend Pritzker Psychiatry Building — San Francisco

Publications

• Denys D. Pharmacotherapy of obsessive-compulsive disorder and obsessive-compulsive spectrum disorders. Psychiatr Clin North Am. 2006 Jun;29(2):553-84, xi. doi: 10.1016/j.psc.2006.02.013. PMID 16650723
• 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
• Swann NC, de Hemptinne C, Thompson MC, Miocinovic S, Miller AM, Gilron R, Ostrem JL, Chizeck HJ, Starr PA. Adaptive deep brain stimulation for Parkinson's disease using motor cortex sensing. J Neural Eng. 2018 Aug;15(4):046006. doi: 10.1088/1741-2552/aabc9b. Epub 2018 May 9. PMID 29741160
• Starr PA. Totally Implantable Bidirectional Neural Prostheses: A Flexible Platform for Innovation in Neuromodulation. Front Neurosci. 2018 Sep 7;12:619. doi: 10.3389/fnins.2018.00619. eCollection 2018. PMID 30245616
• Dougherty DD, Brennan BP, Stewart SE, Wilhelm S, Widge AS, Rauch SL. Neuroscientifically Informed Formulation and Treatment Planning for Patients With Obsessive-Compulsive Disorder: A Review. JAMA Psychiatry. 2018 Oct 1;75(10):1081-1087. doi: 10.1001/jamapsychiatry.2018.0930. PMID 30140845
• Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012 Jan;16(1):43-51. doi: 10.1016/j.tics.2011.11.003. Epub 2011 Dec 2. PMID 22138231
• Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, Repovs G, Cole MW, Bednarski S, Krystal JH, Bloch MH, Li CS, Pittenger C. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry. 2014 Apr 15;75(8):595-605. doi: 10.1016/j.biopsych.2013.10.021. Epub 2013 N PMID 24314349
• Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan M, Alborzian S, Phelps ME, Baxter LR Jr. Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder. Neuropsychopharmacology. 1999 Dec;21(6):683-93. doi: 10.1016/S0893-133X(99)00082-2. PMID 10633474

Identifiers

NCT: NCT04958096 · 21-33743

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗