Adaptive Deep Brain Stimulation for Obsessive-Compulsive Disorder

Recruiting at 2 trial locations

Overseen By Nithya Ramakrishnan, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: SSRIs, Antipsychotics

Disqualifiers: Psychotic disorders, Substance abuse, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 months

5 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 and 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 (DBS) 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 DBS 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 II which will implant the RC+S system with ECoG paddles in 5 subjects.

Will I have to stop taking my current medications?

The trial requires that participants have a stable psychotropic medication regimen for the month before surgery, so you may need to continue your current medications if they are stable. The protocol does not specify if you must stop any medications, but it seems you should maintain your current regimen.

What data supports the effectiveness of the treatment Adaptive Deep Brain Stimulation for Obsessive-Compulsive Disorder?

Research shows that deep brain stimulation (DBS) can significantly reduce symptoms in patients with treatment-resistant obsessive-compulsive disorder (OCD). Studies have demonstrated that DBS targeting specific brain areas, like the ventral striatum and nucleus accumbens, leads to substantial improvements in OCD symptoms, with some patients experiencing over 50% reduction in symptoms. ^{1 2 3 4 5}

Is Adaptive Deep Brain Stimulation safe for humans?

Deep Brain Stimulation (DBS) for obsessive-compulsive disorder (OCD) has shown that most adverse events (side effects) are mild or moderate and often resolve with adjustments. However, some serious events like mood changes and surgery-related issues have been reported, but overall, DBS is considered promising and relatively safe for treatment-resistant OCD. ^{6 7 8 9 10}

How is Adaptive Deep Brain Stimulation different from other treatments for OCD?

Adaptive Deep Brain Stimulation (aDBS) is unique because it uses a closed-loop system that responds to real-time brain activity, specifically targeting the ventral striatum to adjust stimulation based on symptom fluctuations. This personalized approach contrasts with traditional deep brain stimulation, which provides constant stimulation without adapting to changes in the patient's symptoms. ^{1 2 3 4 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 history of at least five years of difficult-to-treat OCD and significant distress or impairment due to the disorder.

Inclusion Criteria

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

I have tried clomipramine for my condition but it didn't work or caused side effects.

I've tried and didn't respond to certain medications with added antipsychotics.

Exclusion Criteria

I am not pregnant and do not plan to become pregnant in the next 2 years.

You require the use of diathermy during the study.

You have been assessed by a doctor and they believe you are at high risk of acting impulsively or having thoughts of self-harm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

2 visits (in-person)

Treatment

Subjects undergo surgical implantation of RC+S DBS system with ECoG paddles and subsequent programming and monitoring

12 months

Multiple visits for surgery, programming, and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of mood and anxiety

6 months

Regular follow-up visits

Blinded Discontinuation Period

Subjects undergo a one-month blinded discontinuation period to assess the effects of DBS discontinuation

4 weeks

Weekly visits

Treatment Details

Interventions

• Adaptive Deep Brain Stimulation

Trial Overview The study tests an adaptive Deep Brain Stimulation (aDBS) system using the Summit RC+S System with ECoG paddles in subjects with hard-to-control OCD. The goal is to improve brain targeting for DBS and find a more effective treatment method for OCD.

Participant Groups

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

All subjects will receive surgical implantation of RC+S DBS system with ECoG paddles

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

Brown University

Collaborator

Trials

480

Recruited

724,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Findings from Research

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) shows promise as a safe and effective treatment for patients with treatment-resistant obsessive-compulsive disorder (OCD), with average reductions in Yale-Brown Obsessive Compulsive Scale scores ranging from 6.8 to 31 points across small studies.

Approximately 50% of patients respond positively to DBS, and the frequency of adverse events appears to be limited, indicating that it could be a viable option for those who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets. de Koning, PP., Figee, M., van den Munckhof, P., et al.[2021]

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) 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) 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]

References

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

Electrophysiological and imaging evidence of sustained inhibition in limbic and frontal networks following deep brain stimulation for treatment refractory obsessive compulsive disorder. [2020]

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

Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Patient specific intracranial neural signatures of obsessions and compulsions in the ventral striatum. [2023]

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

Deep Brain Stimulation Reduces Conflict-Related Theta and Error-Related Negativity in Patients With Obsessive-Compulsive Disorder. [2022]

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

A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder. [2021]

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

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

Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets. [2021]

9. 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]

10. 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]

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

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