Deep Brain Stimulation for Obsessive-Compulsive Disorder

Recruiting at2 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Casey H. Halpern, M.D.

Must be taking: SSRIs, Antipsychotics, Clomipramine

Disqualifiers: Personality disorder, Bipolar, Eating disorders, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a device that sends electrical signals to the brain in patients with severe OCD who don't respond to usual treatments. The electrical pulses aim to help control OCD symptoms. This experimental treatment has shown promising results for severe OCD.

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 data supports the idea that Deep Brain Stimulation for Obsessive-Compulsive Disorder is an effective treatment?

The available research shows that Deep Brain Stimulation (DBS) is effective for patients with severe Obsessive-Compulsive Disorder (OCD) who have not responded to other treatments. Studies have shown that DBS can lead to long-term improvements in symptoms and overall well-being. It has been approved by the U.S. FDA for severe cases of OCD, indicating its recognized effectiveness. While other treatments like medication and therapy are often tried first, DBS is considered a last resort for those who do not benefit from these options. The research also suggests that DBS works by targeting specific brain circuits involved in OCD, which helps reduce symptoms. ^{1 2 3 4 5}

What safety data is available for deep brain stimulation in treating OCD?

Several studies provide safety data for deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD). A prospective international multi-center study reported that all patients experienced adverse events (AEs), with most being mild or moderate and resolving within 22 days. Serious adverse events (SAEs) were mainly transient anxiety and affective symptoms worsening. The study concluded that the potential benefits of DBS outweigh the risks in a treatment-resistant population. Additionally, a systematic review and meta-analysis evaluated the safety of DBS for OCD, indicating that while serious adverse events can occur, they are generally manageable and related to programming or stimulation adjustments. ^{1 3 4 6 7}

Is Deep Brain Stimulation a promising treatment for Obsessive-Compulsive Disorder?

Yes, Deep Brain Stimulation (DBS) is a promising treatment for Obsessive-Compulsive Disorder (OCD), especially for those who do not respond to standard therapies. It involves placing electrodes in the brain to help control symptoms in a new way compared to traditional treatments like therapy or medication. Studies show that DBS can be effective in improving the well-being and functioning of patients with severe OCD. ^{3 8 9 10 11}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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.

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+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

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) 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) 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]

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]

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]

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) 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) 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 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]

References

1. United States 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. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Obsessive Compulsive Disorder: Evolution of Surgical Stimulation Target Parallels Changing Model of Dysfunctional Brain Circuits. [2020]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. [2022]

7. United States 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. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise. [2023]

9. United States 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. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions. [2023]

11. Scotland 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. [2022]