Cortical Stimulation to Treat Obsessive Compulsive Disorder

NCT04958096 | Recruiting FDA Device

• 1 other identifier: 21-33743
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Obsessive-Compulsive Disorder

Keywords

OCD; Obsessive Compulsive Disorder; Obsessive thoughts; Compulsions

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  12-24 months

Other Outcomes (1)

• Biomarker identification in Stage 1

  1-12 months

Study Arms (2)

Prefrontal Cortex (PFC)

EXPERIMENTAL

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; Device: Cortical Stimulation for PFC

Anterior Cingulate Cortex (ACC)

EXPERIMENTAL

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; Device: Cortical Stimulation for ACC

Interventions

Standard Therapeutic Deep Brain Stimulation DEVICE

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

Anterior Cingulate Cortex (ACC); Prefrontal Cortex (PFC)

Cortical Stimulation for PFC DEVICE

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

Also known as: PFC Stimulation

Prefrontal Cortex (PFC)

Cortical Stimulation for ACC DEVICE

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

Also known as: OCD Cortical Stimulation

Anterior Cingulate Cortex (ACC)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Andrew Moses Lee, MD, PhD: lead

Study Sites (1)

UCSF Nancy Friend Pritzker Psychiatry Building

San Francisco, California, 94107, United States

RECRUITING

Related Publications (28)

• 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 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

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 Nov 4.

  PMID: 24314349 BACKGROUND

• 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 BACKGROUND

• Nabeyama M, Nakagawa A, Yoshiura T, Nakao T, Nakatani E, Togao O, Yoshizato C, Yoshioka K, Tomita M, Kanba S. Functional MRI study of brain activation alterations in patients with obsessive-compulsive disorder after symptom improvement. Psychiatry Res. 2008 Aug 30;163(3):236-47. doi: 10.1016/j.pscychresns.2007.11.001. Epub 2008 Jul 29.

  PMID: 18667293 BACKGROUND

• Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000 Sep;23(3):563-86. doi: 10.1016/s0193-953x(05)70181-7.

  PMID: 10986728 BACKGROUND

• Brown LT, Mikell CB, Youngerman BE, Zhang Y, McKhann GM 2nd, Sheth SA. Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: a systematic review of observational studies. J Neurosurg. 2016 Jan;124(1):77-89. doi: 10.3171/2015.1.JNS14681. Epub 2015 Aug 7.

  PMID: 26252455 BACKGROUND

• Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):931-938. doi: 10.1176/appi.ajp.2019.18101180. Epub 2019 May 21.

  PMID: 31109199 BACKGROUND

• Nauczyciel C, Le Jeune F, Naudet F, Douabin S, Esquevin A, Verin M, Dondaine T, Robert G, Drapier D, Millet B. Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study. Transl Psychiatry. 2014 Sep 9;4(9):e436. doi: 10.1038/tp.2014.62.

  PMID: 25203167 BACKGROUND

• Rao VR, Sellers KK, Wallace DL, Lee MB, Bijanzadeh M, Sani OG, Yang Y, Shanechi MM, Dawes HE, Chang EF. Direct Electrical Stimulation of Lateral Orbitofrontal Cortex Acutely Improves Mood in Individuals with Symptoms of Depression. Curr Biol. 2018 Dec 17;28(24):3893-3902.e4. doi: 10.1016/j.cub.2018.10.026. Epub 2018 Nov 29.

  PMID: 30503621 BACKGROUND

• Sani OG, Yang Y, Lee MB, Dawes HE, Chang EF, Shanechi MM. Mood variations decoded from multi-site intracranial human brain activity. Nat Biotechnol. 2018 Nov;36(10):954-961. doi: 10.1038/nbt.4200. Epub 2018 Sep 10.

  PMID: 30199076 BACKGROUND

• Bijanki KR, Manns JR, Inman CS, Choi KS, Harati S, Pedersen NP, Drane DL, Waters AC, Fasano RE, Mayberg HS, Willie JT. Cingulum stimulation enhances positive affect and anxiolysis to facilitate awake craniotomy. J Clin Invest. 2019 Mar 1;129(3):1152-1166. doi: 10.1172/JCI120110. Epub 2019 Feb 11.

  PMID: 30589643 BACKGROUND

• Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Ostrem JL, Galifianakis NB, Luciano MS, Wang SS, Ziman N, Taylor R, Starr PA. Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease. J Neurosurg. 2018 Feb;128(2):605-616. doi: 10.3171/2016.11.JNS161162. Epub 2017 Apr 14.

  PMID: 28409730 BACKGROUND

• Shirvalkar P, Veuthey TL, Dawes HE, Chang EF. Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain. Front Comput Neurosci. 2018 Mar 26;12:18. doi: 10.3389/fncom.2018.00018. eCollection 2018.

  PMID: 29632482 BACKGROUND

• De Ridder D, Leong SL, Manning P, Vanneste S, Glue P. Anterior Cingulate Implant for Obsessive-Compulsive Disorder. World Neurosurg. 2017 Jan;97:754.e7-754.e16. doi: 10.1016/j.wneu.2016.10.046. Epub 2016 Oct 15.

  PMID: 27756670 BACKGROUND

• Burguiere E, Monteiro P, Feng G, Graybiel AM. Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science. 2013 Jun 7;340(6137):1243-6. doi: 10.1126/science.1232380.

  PMID: 23744950 BACKGROUND

• Pinhal CM, van den Boom BJG, Santana-Kragelund F, Fellinger L, Bech P, Hamelink R, Feng G, Willuhn I, Feenstra MGP, Denys D. Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice. Biol Psychiatry. 2018 Dec 15;84(12):917-925. doi: 10.1016/j.biopsych.2018.05.011. Epub 2018 May 23.

  PMID: 29954580 BACKGROUND

• Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS, Shapira NA, Foote KD, Cosyns PR, Kubu CS, Malloy PF, Salloway SP, Giftakis JE, Rise MT, Machado AG, Baker KB, Stypulkowski PH, Goodman WK, Rasmussen SA, Nuttin BJ. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010 Jan;15(1):64-79. doi: 10.1038/mp.2008.55. Epub 2008 May 20.

  PMID: 18490925 BACKGROUND

• Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Wang SS, Ziman N, Ostrem JL, San Luciano M, Galifianakis NB, Starr PA. Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease. J Neurosci. 2016 Jun 15;36(24):6445-58. doi: 10.1523/JNEUROSCI.1128-16.2016.

  PMID: 27307233 BACKGROUND

• Brown JA, Barbaro NM. Motor cortex stimulation for central and neuropathic pain: current status. Pain. 2003 Aug;104(3):431-435. doi: 10.1016/S0304-3959(03)00209-4. No abstract available.

  PMID: 12927615 BACKGROUND

• Brown JA, Lutsep H, Cramer SC, Weinand M. Motor cortex stimulation for enhancement of recovery after stroke: case report. Neurol Res. 2003 Dec;25(8):815-8. doi: 10.1179/016164103771953907.

  PMID: 14669524 BACKGROUND

• Panov F, Kopell BH. Use of cortical stimulation in neuropathic pain, tinnitus, depression, and movement disorders. Neurotherapeutics. 2014 Jul;11(3):564-71. doi: 10.1007/s13311-014-0283-0.

  PMID: 24888372 BACKGROUND

• Kimmelman J, Duckworth K, Ramsay T, Voss T, Ravina B, Emborg ME. Risk of surgical delivery to deep nuclei: a meta-analysis. Mov Disord. 2011 Jul;26(8):1415-21. doi: 10.1002/mds.23770. Epub 2011 May 14.

  PMID: 21574186 BACKGROUND

• Panov F, Levin E, de Hemptinne C, Swann NC, Qasim S, Miocinovic S, Ostrem JL, Starr PA. Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases. J Neurosurg. 2017 Jan;126(1):122-131. doi: 10.3171/2015.11.JNS151341. Epub 2016 Feb 26.

  PMID: 26918474 BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder; Compulsive Behavior

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders; Impulsive Behavior; Behavior

Study Officials

• Andrew M Lee, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew M Lee, MD, PhD

CONTACT

415-502-5472; ocdresearch@ucsf.edu

Tenzin Norbu, BS

CONTACT

415-514-6489; ocdresearch@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Psychiatry

Study Record Dates

• First Submitted: June 27, 2021
• First Posted: July 12, 2021
• Study Start: August 1, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)