Deep Brain Stimulation for Obsessive-Compulsive Disorder

(Phase Ib Trial)

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: SSRIs, Antipsychotics

Disqualifiers: Schizophrenia, Substance abuse, Neurological disorders, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an adaptive Deep Brain Stimulation (aDBS) system for individuals with severe Obsessive-Compulsive Disorder (OCD) that hasn't improved with other treatments. OCD can be disabling, causing repetitive behaviors and distressing thoughts that affect daily life. Participants will have the Summit RC+S System surgically implanted in the brain to help restore balance to brain circuits believed to be involved in OCD. The researchers aim to find a better, more reliable way to treat OCD symptoms. Individuals who have struggled with OCD for at least five years and haven't found relief from medications or therapy may be a good fit for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatment options for those who have not found success with existing therapies.

Will I have to stop taking my current medications?

The trial requires that participants have a stable medication regimen for at least one month before surgery, so you may not need to stop your current medications if they are stable. However, it's best to discuss your specific situation with the study team.

What prior data suggests that this deep brain stimulation system is safe for treating OCD?

Research shows that deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) usually causes mild to moderate side effects, which often resolve on their own. Studies have found that DBS can be safely used in everyday settings for OCD and offers long-term benefits. Although researchers are still testing the Summit RC+S System, earlier studies suggest it is generally well-tolerated. Prospective participants should always consult a healthcare professional about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Summit RC+S System for treating Obsessive-Compulsive Disorder (OCD) because it offers a unique approach compared to standard options like cognitive-behavioral therapy and medications such as SSRIs. Unlike these treatments, which can take weeks to show effects and primarily work through altering brain chemistry, the Summit RC+S System uses deep brain stimulation (DBS) to directly target brain circuits involved in OCD. This method allows for real-time adjustments and potentially faster relief of symptoms. Furthermore, the study includes a one-month blinded discontinuation period to observe how changes in stimulation levels affect symptoms, providing valuable insights into the treatment's effectiveness and resilience against relapse.

What evidence suggests that this adaptive Deep Brain Stimulation system is effective for treating intractable OCD?

Research shows that deep brain stimulation (DBS) can alleviate symptoms in people with obsessive-compulsive disorder (OCD). Studies have found that DBS improves overall functioning and reduces symptoms for many patients, even those with additional health issues. Approximately 50% of individuals treated with DBS for OCD experience positive results. However, outcomes can vary significantly among individuals. In this trial, all participants will receive the Summit RC+S System, which aims to enhance these outcomes by refining the DBS method, potentially offering more consistent benefits for those with severe OCD. ^{3 4 6 7 8}

Who Is on the Research Team?

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 21-70 with severe OCD that hasn't improved after trying many treatments, including cognitive-behavioral therapy and various medications. Participants must have a significant history of OCD symptoms causing distress and dysfunction. They cannot join if they have neurological disorders, high suicide risk, MRI contraindications, psychotic disorders like schizophrenia, or are pregnant.

Inclusion Criteria

I have completed 25 hours of a specific therapy for OCD without success.

I am between 21 and 70 years old.

Your score on the Y-BOCS test must be at least 28.

Exclusion Criteria

Pregnant (confirmed by serum pregnancy test on females of child bearing age) or plans to become pregnant in the next 24 months

You score 8 or higher on a test that measures obsessive-compulsive behaviors.

Non-Implanted Control Subject Exclusion criteria:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

2 visits (in-person)

Treatment

Subjects undergo DBS implantation and initial programming, including pre-surgical imaging and post-operative monitoring

6 months

Multiple visits for surgery and follow-up

Blinded Discontinuation

One month period where DBS is gradually reduced and then turned off to assess effects

4 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Summit RC+S System

Trial Overview The study aims to develop an adaptive Deep Brain Stimulation (aDBS) system for patients with hard-to-treat OCD. It involves surgically implanting electrodes in the brain connected to a chest device that sends electrical currents to alter brain function. The Phase Ib will involve implanting the RC+S system in two subjects.

How Is the Trial Designed?

Group I: Summit RC+S DBS Implant for OCD Experimental Treatment 1 Intervention

all subjects will receive surgical implantation of DBS system

Group II: One Month Blinded Discontinuation Period Experimental Treatment 1 Intervention

The subject and Independent Evaluators are blinded to timing of discontinuation. In all cases, the sequence will be as follows in one-week segments: 100% Active, 50% Active, Sham and Sham. Subjects will be seen weekly. Amplitude will be reduced by 50% at start of week 2 and turned off at start of week 3. Subjects will be told that DBS will be discontinued at some point during the 4 weeks. The purpose of the 50% initial reduction is to minimize rebound effects. The programmer (not the PI in this case) will be open to the design and perform "sham" activation as described previously. Relapse is defined as a 25% increase of the Y-BOCS over two consecutive visits compared to discontinuation baseline

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Carnegie Mellon University

Collaborator

Trials

80

Recruited

540,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Published Research Related to This Trial

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) for treatment-resistant obsessive-compulsive disorder (OCD) has been associated with various adverse events, with psychiatric issues being the most common (40%), followed by neurological problems (19%) and infections (10%).

The study highlights that while DBS may be a viable treatment option for certain patients with refractory OCD, ongoing monitoring and further research are necessary to fully understand the long-term safety and efficacy of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for refractory obsessive-compulsive disorder: A review and analysis of the FDA MAUDE database. Porwal, MH., Karra, H., Sharma, U., 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]

In a pilot study involving six patients with severe, treatment-resistant OCD, 66.7% showed significant improvement after 12 months of deep brain stimulation (DBS) targeting the ventral capsule/ventral striatum, indicating its potential as a last-resort therapy.

The study reported that while DBS led to improvements in OCD symptoms and global functioning, some patients experienced mild adverse effects, and stimulation interruption could quickly induce depressive symptoms, highlighting the need for careful patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design. Goodman, WK., Foote, KD., Greenberg, BD., et al.[2022]

Deep brain stimulation (DBS) of the subthalamic nucleus can significantly reduce the severity of symptoms in patients with severe and persistent Obsessive Compulsive Disorder (OCD), especially in those who do not respond to traditional treatments.

DBS not only helps alleviate OCD symptoms but also enhances overall functioning, providing insights into the underlying mechanisms of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[OCD: when limbic systems start looping...]. Flores Alves dos Santos, J., Mallet, L.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7058594/

Deep Brain Stimulation for Obsessive–Compulsive Disorder Deep brain stimulation (DBS) is a proven, effective tool in the treatment of movement disorders. Expansion of indications for DBS into the realm ...

2. withpower.com withpower.com/trial/phase-compulsive-personality-disorder-9-2019-11214

Deep Brain Stimulation for Obsessive-Compulsive ... The study reported that while DBS led to improvements in OCD symptoms and global functioning, some patients experienced mild adverse effects, and stimulation ...

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.568932/full

Deep Brain Stimulation for Obsessive-Compulsive Disorder DBS remains an efficacious tool for the treatment of OCD, even in patients with significant comorbidities in whom DBS has not previously been investigated.

4. sciencedirect.com sciencedirect.com/science/article/pii/S089662732300747X

Responsive deep brain stimulation guided by ventral ... Although DBS approximately achieves a 50% response rate, patient outcomes are markedly heterogeneous. Failure to achieve consistent outcomes is ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10387502/

Tractography-Based Modeling Explains Treatment ... We provide data in a first-of-its kind report suggesting that normative tractography-based modeling can blindly predict treatment response in DBS for OCD.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04281134?tab=table

Development of Adaptive Deep Brain Stimulation for OCD ... The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8800455/

Long-term ecological assessment of intracranial ... Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in Obsessive-Compulsive Disorder

8. withpower.com withpower.com/trial/phase-compulsive-personality-disorder-6-2021-f00fa

Adaptive Deep Brain Stimulation for Obsessive ... Deep Brain Stimulation (DBS) for obsessive-compulsive disorder (OCD) has shown that most adverse events (side effects) are mild or moderate and often resolve ...