Deep Brain Stimulation for Obsessive-Compulsive Disorder

(Phase Ib Trial)

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

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is for participants that have been diagnosed with intractable Obsessive -compulsive disorder (OCD). OCD is a persistent and oftentimes disabling disorder marked by unwanted and distressing thoughts (obsessions) and irresistible repetitive behaviors. OCD affects 2-3% of the US population, and is responsible for substantial functional impairment and increased risk of early death. The only established first-line treatments for OCD are cognitive-behavioral therapy (CBT) with exposure/response prevention and certain medications. About 30-40% of patients fail to respond and few experience complete symptom resolution. Up to 25% of patients have difficulty tolerating CBT and the risk of relapse after therapies remains large. For the most severe cases, neurosurgery (surgery in the brain), has long been the option of last resort. In this study the investigators want develop an adaptive Deep Brain Stimulation (aDBS) system to use in subjects with intractable (hard to control) OCD. Deep brain stimulation remains investigational for OCD patients and is not considered standard therapy. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed deep brain stimulation may restore balance to dysfunctional brain circuitry implicated in 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 OCD treatment. This current research protocol will focus on the completion of Phase Ib which will implant the RC+S system in 2 subjects.

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 data supports the effectiveness of the treatment Summit RC+S System for Obsessive-Compulsive Disorder?

Research shows that deep brain stimulation (DBS) can reduce the severity of symptoms and improve overall functioning in people with severe OCD who do not respond to other treatments. Studies have found DBS to be a promising option for those with treatment-resistant OCD, particularly when targeting specific brain areas like the subthalamic nucleus. ^{1 2 3 4 5}

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) has been studied for safety, showing that while some serious side effects can occur, most are mild or moderate and often resolve with adjustments. Common issues include anxiety and mood changes, but these are usually temporary. Serious surgery-related problems like bleeding or infection are rare. ^{2 6 7 8 9}

How is the Summit RC+S System treatment different from other treatments for obsessive-compulsive disorder?

The Summit RC+S System uses deep brain stimulation (DBS), which involves implanting electrodes in specific brain areas to help manage severe OCD symptoms when other treatments have failed. This approach is unique because it directly targets brain circuits involved in OCD, offering a potential option for those who do not respond to conventional therapies. ^{2 3 4 10 11}

Research Team

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

Non-Implanted Control Subject Exclusion criteria:

Inability or refusal to give informed consent

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

[OCD: when limbic systems start looping...]. [2013]

2. 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]

3. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study. [2016]

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

Deep brain stimulation for refractory obsessive-compulsive disorder: A review and analysis of the FDA MAUDE database. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for obsessive-compulsive disorder: A systematic review of randomised controlled trials. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Six-Nine Year Follow-Up of Deep Brain Stimulation for Obsessive-Compulsive Disorder. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for obsessive-compulsive disorder: A systematic review of worldwide experience after 20 years. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Identity challenges and 'burden of normality' after DBS for severe OCD: a narrative case study. [2019]