Deep Brain Stimulation for Obsessive-Compulsive Disorder

Recruiting in Palo Alto (17 mi)

+2 other 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}

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stanford University Stanford, CA

University of Pennsylvania Philadelphia, PA

University of California San Francisco, CA

Who Is Running the Clinical Trial?

Casey H. Halpern, M.D. Lead Sponsor

Stanford University Collaborator

University of California, San Francisco Collaborator

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] In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice.

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] Obsessive compulsive disorder (OCD) is a common, disabling psychiatric disease characterized by persistent, intrusive thoughts and ritualistic, repetitive behaviors. Deep brain stimulation (DBS) is thought to alleviate OCD symptoms by modulating underlying disturbances in normal cortico-striato-thalamo-cortical (CSTC) circuitry. Stimulation of the ventral portion of the anterior limb of the internal capsule (ALIC) and underlying ventral striatum ("ventral capsule/ventral striatum" or "VC/VS" target) received U.S. FDA approval in 2009 for patients with severe, treatment-refractory OCD. Over the decades, DBS surgical outcome studies have led to an evolution in the electrical stimulation target. In parallel, advancements in neuroimaging techniques have allowed investigators to better visualize and define CSTC circuits underlying the pathophysiology of OCD. A critical analysis of these new data suggests that the therapeutic mechanism of DBS for OCD likely involves neuromodulation of a widespread cortical/subcortical network, accessible by targeting fiber bundles in the ventral ALIC that connect broad network regions. Future studies will include advances in structural and functional imaging, analysis of physiological recordings, and utilization of next-generation DBS devices. These tools will enable patient-specific optimization of DBS therapy, which will hopefully further improve outcomes.

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] Deep brain stimulation (DBS) is an effective intervention for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Our aim was to examine long-term effectiveness and tolerability of DBS and its impact on functioning and well-being.

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

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder. [2021] Deep brain stimulation (DBS) is cleared for treatment of obsessive-compulsive disorder (OCD) but is an investigational treatment for major depressive disorder (MDD). The aim of this study is to compare the characteristics of patients who received DBS as part of standard care for OCD versus those who received it a part of a research protocol for MDD.

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

Deep brain stimulation in the treatment of obsessive-compulsive disorder: current perspectives. [2020] Deep brain stimulation (DBS) is a neuro-psychosurgical technique widely accepted in movement disorders, such as Parkinson's disease. Since 1999, DBS has been explored for severe, chronic and treatment-refractory psychiatric diseases. Our review focuses on DBS in obsessive-compulsive disorder (OCD), considered as a last treatment resort by most of learned societies in psychiatry. Two main stimulation areas have been studied: the striatal region and the subthalamic nucleus. But, most of the trials are open-labeled, and the rare controlled ones have failed to highlight the most efficient target. The recent perspectives are otherwise encouraging. Indeed, clinicians are currently considering other promising targets. A case series of 2 patients reported a decrease in OCD symptoms after DBS in the medial forebrain bundle and an open-label study is exploring bilateral habenula stimulation. New response criteria are also investigating such as quality of life, or subjective and lived-experience. Moreover, first papers about cost-effectiveness which is an important criterion in decision making, have been published. The effectiveness of tractography-assisted DBS or micro-assisted DBS is studying with the aim to improve targeting precision. In addition, a trial involving rechargeable pacemakers is undergoing because this mechanism could be efficient and have a positive impact on cost-effectiveness. A recent trial has discussed the possibility of using combined cognitive behavioral therapy (CBT) and DBS as an augmentation strategy. Finally, based on RDoc Research, the latest hypotheses about the understanding of cortico-striato-thalamo-cortical circuits could offer new directions including clinical predictors and biomarkers to perform adaptive closed-loop systems in the next future.

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] Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

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] To evaluate efficacy, effect on mood, and safety of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) at different target sites.

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

Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise. [2023] Deep brain stimulation (DBS) is an innovative treatment for severe obsessive-compulsive disorder (OCD). Electrodes implanted in specific brain areas allow clinicians to directly modulate neural activity. DBS affects symptomatology in a completely different way than established forms of treatment for OCD, such as psychotherapy or medication.

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] Deep brain stimulation (DBS) is an effective treatment for patients with obsessive-compulsive disorder (OCD) that do not respond to conventional therapies. Although the precise mechanism of action of DBS remains unknown, modulation of activity in corticofugal fibers originating in the prefrontal cortex is thought to underlie its beneficial effects in OCD.

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] Obsessive-compulsive disorder (OCD) affects 2-3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution.

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] Deep brain stimulation (DBS) is considered a promising intervention for treatment-resistant obsessive-compulsive disorder (OCD). The present study describes the outcomes of the first DBS procedures for OCD in Iran.