Deep Brain Stimulation for Obsessive-Compulsive Disorder

Recruiting at 2 trial locations

Overseen By Nida Firdous, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Casey H. Halpern, M.D.

Must be taking: SSRIs, Antipsychotics, Clomipramine

Disqualifiers: Personality disorder, Bipolar, Eating disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new approach for individuals with severe obsessive-compulsive disorder (OCD) who haven't found relief from standard treatments. It employs deep brain stimulation (DBS), where a device sends electrical signals to specific brain areas to reduce OCD symptoms. The trial includes a phase where the stimulation alternates between on and off to assess its effectiveness. Suitable candidates have experienced OCD for over five years, with symptoms significantly disrupting daily life. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for those seeking new solutions.

Do I need to stop my current medications to join the trial?

No, you don't need to stop your current medications. In fact, you must stay on the same daily dose of any psychotropic medications for at least 8 weeks before joining and throughout the trial.

What prior data suggests that this SEEG-guided DBS is safe for treating OCD?

Research has shown that deep brain stimulation (DBS) has been explored as a treatment for obsessive-compulsive disorder (OCD) and is generally considered safe. Studies have found that using stereoencephalography (SEEG) to guide DBS is a safe and practical approach. Although these studies don't provide exact numbers, they indicate that patients handle this treatment well.

SEEG-guided DBS involves placing small wires in the brain to help manage OCD symptoms. In the past, patients have mostly experienced minor issues, such as headaches or temporary discomfort after the procedure. Serious side effects are rare but can include infection or bleeding.

Overall, DBS has been used for other conditions, and the results so far for OCD are promising in terms of safety and patient tolerance. However, discussing potential risks and benefits with healthcare providers is important before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) for Obsessive-Compulsive Disorder (OCD) because it targets specific brain circuits responsible for OCD symptoms, offering a new approach compared to traditional treatments like cognitive-behavioral therapy (CBT) and medication. Unlike standard treatments that can take weeks or months to show results, DBS has the potential to provide quicker symptom relief by directly modulating brain activity. The Vercise Genus™ DBS System, guided by PMT Stereoencephalography (SEEG), allows for precise targeting and adjustment of stimulation, which could lead to more effective and personalized treatment outcomes for patients struggling with severe OCD.

What evidence suggests that SEEG-guided DBS is effective for OCD?

Research has shown that SEEG-guided DBS (deep brain stimulation) might help people with OCD (obsessive-compulsive disorder) who haven't responded to other treatments. This trial will compare two approaches: the SEEG Guided DBS ON-OFF (Stimulation-Sham) arm and the SEEG Guided DBS OFF-ON (Sham-Stimulation) arm. This method targets specific brain areas linked to OCD, potentially leading to better outcomes. Early studies suggest that SEEG-guided DBS can reduce OCD symptoms by improving brain stimulation. This approach aims to tailor treatment by identifying the best brain areas for stimulation. Although still under study, initial findings suggest it could be a safe and effective option for those not responding to other treatments. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 22-65 with severe, treatment-resistant Obsessive-Compulsive Disorder (OCD), having tried multiple medications and cognitive therapy without success. Participants must be able to follow the study's procedures in English, live within a 6-hour drive of the study sites, have stable housing and support, and commit to no psychotherapy or medication changes during the trial.

Inclusion Criteria

I have completed a full course of ERP therapy for my condition.

I am between 22 and 75 years old.

Lack of adequate response to a history of the following treatments, based on information from any of the following: (a) the current treating physician and/or psychologist; (b) medical records or other forms of communication from previous healthcare providers; and (c) pharmacy records, as determined by the Principal Investigator

Exclusion Criteria

History of involuntary movements, in the opinion of the Principal Investigator or a neuro-radiologist

Diagnosis of, according to the Mini International Neuropsychiatric Interview (MINI), any other primary psychiatric diagnosis defined in the DSM-5, including Hoarding Disorder

I have not been treated for drug or alcohol abuse in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SEEG Brain Mapping and Optimization

SEEG brain mapping and optimization of stimulation parameters

2 weeks

DBS Surgery and Optimization

DBS surgery and further optimization of stimulation parameters

14 days

Randomized Crossover Treatment

Randomized crossover treatment with active and sham conditions

12 weeks

Open Label Treatment

Open label stimulation for an additional 6 months

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PMT Stereoencephalography (SEEG)
• SEEG-Guided DBS
• Vercise Genus™ Deep Brain Stimulation (DBS) System

Trial Overview The trial tests SEEG-guided Deep Brain Stimulation (DBS) using Vercise Genus™ System on those with severe OCD. It involves brain mapping, DBS surgery, parameter optimization, randomized crossover treatment phases followed by open label stimulation over approximately an 18-month period.

How Is the Trial Designed?

Group I: SEEG Guided DBS ON-OFF (Stimulation-Sham) Experimental Treatment 2 Interventions

Patients in the ON-OFF arm will first be treated for up to 12 weeks with the parameters identified during the DBS optimization phase until the washout period.

Group II: SEEG Guided DBS OFF-ON (Sham-Stimulation) Placebo Group 2 Interventions

Patients in the OFF-ON will have their devices turned off and will not have their device switched on (activated) until the crossover point.

PMT Stereoencephalography (SEEG) is already approved in United States for the following indications:

Approved in United States as SEEG-Guided DBS for:

• Treatment-refractory Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

Casey H. Halpern, M.D.

Lead Sponsor

Trials

1

Recruited

10+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Deep brain stimulation (DBS) is an approved treatment for obsessive-compulsive disorder (OCD) but is still investigational for major depressive disorder (MDD), highlighting the need for more research to establish its efficacy for MDD.

Patients receiving DBS for OCD were generally younger and had different regional distributions compared to those with MDD, who were typically older and from higher-income families, indicating demographic differences that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder. Youssef, NA., Phung, P., Patel, RS.[2021]

In a study of 30 patients with severe, treatment-refractory OCD, deep brain stimulation (DBS) showed a 42% reduction in obsessive-compulsive symptoms after 12 months, with a responder rate of 60%.

While all patients experienced adverse events (195 total), most were mild or moderate, and the serious adverse events were primarily transient anxiety and worsening of affective symptoms, suggesting that the benefits of DBS may outweigh the risks in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. Menchón, JM., Real, E., Alonso, P., et al.[2022]

Deep brain stimulation (DBS) is a novel treatment for severe obsessive-compulsive disorder (OCD) that directly modulates brain activity, offering a different mechanism of action compared to traditional therapies like medication and psychotherapy.

The effectiveness of DBS is evaluated through an interactive process between clinicians and patients, where improvements are seen as increased patient engagement and openness to therapeutic activities, suggesting that DBS can enhance the potential for additional cognitive behavioral therapy (CBT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise. van Westen, M., Rietveld, E., Denys, D.[2023]

Deep brain stimulation (DBS) targeting the internal capsule (IC) significantly reduced excessive grooming behaviors in Sapap3 mutant mice, a model for obsessive-compulsive disorder (OCD), indicating its potential efficacy in treating OCD symptoms.

While both IC and dorsal part of the ventral striatum (dVS) stimulation modulated prefrontal cortical activity, IC-DBS was more effective and also increased locomotion, suggesting a need to balance therapeutic effects with potential side effects in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice. Pinhal, CM., van den Boom, BJG., Santana-Kragelund, F., et al.[2019]

Deep brain stimulation (DBS) in the bed nucleus of stria terminalis (BNST) showed a significant response in 60% of the 10 patients with severe, treatment-resistant OCD, with an average symptom reduction of 53% as measured by the YBOCS scale.

The treatment not only reduced OCD symptoms but also improved depressive symptoms, global functioning, and quality of life, indicating that DBS could be a promising option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions. Abdelnaim, MA., Lang-Hambauer, V., Hebel, T., et al.[2023]

Deep brain stimulation (DBS) for severe treatment-refractory obsessive-compulsive disorder (OCD) showed a significant long-term reduction in OCD symptoms by 39% over an average follow-up of 6.8 years, with half of the patients experiencing a substantial response.

DBS also led to significant improvements in anxiety and depression symptoms, quality of life, and overall functioning, while the unemployment rate decreased from 78% to 58%, indicating enhanced well-being despite some long-term adverse effects like cognitive complaints and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder. Graat, I., Mocking, R., Figee, M., et al.[2021]

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus is recommended over best medical management for patients with treatment-resistant obsessive-compulsive disorder (OCD), based on a systematic review of 10 studies published up to December 2019.

Clinicians may also consider using DBS targeting the nucleus accumbens or bed nucleus of the stria terminalis for OCD, but there is not enough evidence to determine the most effective target for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Deep Brain Stimulations for Obsessive-Compulsive Disorder: Update of the 2014 Guidelines. Staudt, MD., Pouratian, N., Miller, JP., et al.[2022]

Deep brain stimulation (DBS) significantly reduces symptoms of obsessive-compulsive disorder (OCD) and depression, with mean score improvements of -15.0 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and -13.7 on the weighted depression scale at last follow-up, based on a review of 8 randomized controlled trials and 38 observational studies involving a total of 310 participants.

The study found no significant differences in efficacy between different target sites in the brain (limbic vs. non-limbic), and the overall safety profile showed a low rate of adverse events, with an average of 0.68 adverse events per treated patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Effect on Mood Symptoms, and Safety of Deep Brain Stimulation in Refractory Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis. Martinho, FP., Duarte, GS., Couto, FSD.[2020]

Deep brain stimulation (DBS) has been FDA-approved since 2009 for treating severe, treatment-resistant obsessive-compulsive disorder (OCD) by targeting the ventral anterior limb of the internal capsule and ventral striatum, which modulates the brain circuits involved in OCD.

Recent advancements in neuroimaging and understanding of the cortico-striato-thalamo-cortical circuitry suggest that DBS works by neuromodulating a broad network in the brain, and future studies aim to personalize DBS therapy for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Obsessive Compulsive Disorder: Evolution of Surgical Stimulation Target Parallels Changing Model of Dysfunctional Brain Circuits. Karas, PJ., Lee, S., Jimenez-Shahed, J., et al.[2020]

Deep brain stimulation (DBS) in four women with treatment-resistant OCD showed a 19% improvement in obsessive-compulsive symptoms and anxiety after one year, indicating its potential efficacy as a treatment option.

While two patients experienced significant improvements, there were also adverse events, including the emergence of suicidal ideation in two patients, highlighting the need for careful monitoring and consideration of risks associated with DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychopathological and neuropsychological outcomes of deep brain stimulation for severe- treatment-resistant obsessive-compulsive disorder: An open-label case series. Parvaresh-Rizi, M., Ghadirivasfi, M., Babaei, S., et al.[2022]

Deep brain stimulation (DBS) is being explored as a treatment for obsessive-compulsive disorder (OCD) in patients who have not responded to other therapies, with promising results from new targets like the medial forebrain bundle and habenula.

Current research is focusing on improving the precision of DBS targeting and exploring its combination with cognitive behavioral therapy (CBT), as well as assessing cost-effectiveness, which could enhance its clinical application for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives. Tastevin, M., Spatola, G., Régis, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05623306

Study Details | NCT05623306 | SEEG-Guided DBS for OCD This is a multi-site, double-blinded, randomized, crossover study design for SEEG-guided 4-lead DBS for treatment-refractory OCD, followed by open label ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40313293/

Stereo-encephalography-guided multi-lead deep brain ... We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.04.17.25325961v1.full

Stereo-encephalography-guided multi-lead deep brain ... The goal of this study is to assess the safety, feasibility, and preliminary efficacy of multi-lead DBS guided by sEEG in 10 participants ...

4. medrxiv.org medrxiv.org/content/10.1101/2025.04.17.25325961v1.full.pdf

Stereo-encephalography-guided multi-lead deep brain ... SEEG-guided exploration to identify DBS targets for neuromodulation therapy in OCD may enable a personalized understanding of the brain networks ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X23018715

Stereo-EEG-guided network modulation for psychiatric ... This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

6. medrxiv.org medrxiv.org/content/10.1101/2025.04.17.25325961v1

Stereo-encephalography-guided multi-lead deep brain ... We anticipate that sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful ...

7. cceb.med.upenn.edu cceb.med.upenn.edu/crcu/veeva-vault-projects

Veeva Vault Projects | CCEB The SEEG-Guided DBS for OCD is a dual-site, double-blinded, randomized, sham-controlled, crossover study that will assess the safety, feasibility, and ...

8. withpower.com withpower.com/trial/phase-compulsive-personality-disorder-11-2022-b0666

Deep Brain Stimulation for Obsessive-Compulsive Disorder Several studies provide safety data for deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD). ... Group I: SEEG Guided DBS ON-OFF ( ...