Adaptive DBS for Obsessive-Compulsive Disorder

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: SSRIs, Antipsychotics

Disqualifiers: Psychotic disorders, Substance abuse, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

2 Participants Needed

What You Need to Know Before You Apply

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. Phase Ia is to gather data to eventually develop a prototype adaptive DBS system for intractable OCD that uses signals from the brain to automatically adjust the DBS stimulation factors. The overall goal is to improve symptom management and reduce stimulation-induced behavioral side effects.

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 stopping any medications.

Is adaptive DBS 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. In a study with 30 patients, all experienced side effects, but the majority were not severe and were related to the device's programming or stimulation. ^{1 2 3 4 5}

How is the Adaptive DBS treatment for OCD different from other treatments?

Adaptive DBS (deep brain stimulation) for OCD is unique because it involves implanting a device that delivers electrical stimulation to specific brain areas, such as the ventral part of the anterior limb of the internal capsule, to reduce symptoms. This approach is different from traditional treatments like medication or therapy, as it directly targets brain circuits involved in OCD, offering hope for patients who do not respond to other treatments. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Activa PC+S DBS implant for OCD?

Research shows that deep brain stimulation (DBS) can significantly reduce OCD symptoms, with some studies reporting an average improvement of 42% to 73% in symptom severity. Many patients also experience a better quality of life after DBS treatment. ^{1 5 6 7 10}

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 impairment, not be at high risk of suicide or impulsivity, and cannot have other major neurological conditions or be pregnant.

Inclusion Criteria

My OCD wasn't helped by adding antipsychotics to my treatment.

I am between 21 and 70 years old.

I have had OCD for over 5 years, and treatments haven't worked well for me.

Exclusion Criteria

I only have Essential Tremor and no other neurological conditions or brain injuries.

Non-Implanted Control Subject Exclusion criteria: Contraindications to MRI

I am not pregnant.

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 a single stage DBS surgery, followed by post-operative evaluations and device programming

8 weeks

Multiple visits (in-person) for surgery and follow-up

Post-surgical Monitoring

Participants return to clinic every 2 weeks for the first 2 months following system activation for assessments and recordings

8 weeks

Bi-weekly visits (in-person)

CBT Augmentation

Participants receive a two-month cognitive behavioral therapy course starting at Month 7

2 months

Double Blinded Discontinuation

One-month blinded discontinuation period to confirm clinical benefit

1 month

Monthly Programming/Classification/Evaluation

Monthly visits for programming and evaluation from Month 10 to 18

9 months

Monthly visits (in-person)

Long-Term Follow-Up

Device remains implanted for subjects doing well clinically, with follow-up management arranged on a case-by-case basis

At least 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Activa PC+S DBS implant for OCD

Trial Overview The study tests an adaptive Deep Brain Stimulation (aDBS) system in patients with hard-to-treat OCD. It involves surgically placing electrodes in the brain to regulate abnormal activity. The goal is to improve symptom management and reduce side effects by adjusting stimulation based on brain signals.

How Is the Trial Designed?

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

all subjects will enter a one-month blinded discontinuation period to confirm clinical benefit at the end of Month 8.

Group II: Activa PC+S DBS implant for OCD Experimental Treatment 1 Intervention

all subjects will receive surgical implantation of DBS system

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

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

Carnegie Mellon University

Collaborator

Trials

80

Recruited

540,000+

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) 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) 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]

Citations

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

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

2. Austria pubmed.ncbi.nlm.nih.gov

Active stimulation site of nucleus accumbens deep brain stimulation in obsessive-compulsive disorder is localized in the ventral internal capsule. [2016]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder. [2020]

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

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: the search for a valid target. [2023]

5. 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]

6. 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]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. [2023]

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

Integrating precision medicine in the study and clinical treatment of a severely mentally ill person. [2023]