Brain Stimulation for Obsessive-Compulsive Disorder

Recruiting at 1 trial location

Overseen By Andrew M Lee, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Andrew Moses Lee, MD, PhD

Must be taking: SSRIs, Clomipramine, Antipsychotics

Disqualifiers: Hoarding, Severe psychiatric disorder, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore new brain stimulation techniques to treat Obsessive-Compulsive Disorder (OCD). Researchers are examining how certain brain areas, such as the prefrontal cortex and anterior cingulate cortex, function in people with OCD and whether stimulating these areas can improve symptoms. Participants will receive brain implants to monitor brain activity while undergoing standard therapeutic deep brain stimulation. This trial targets individuals who have experienced severe OCD for at least five years and have not found relief from typical treatments like medication and therapy. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in brain stimulation for OCD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since participants must have failed to improve with certain medications, it's possible that you may continue with your current treatment unless advised otherwise by the study team.

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

Research shows that deep brain stimulation (DBS) offers promise for treating severe and hard-to-treat obsessive-compulsive disorder (OCD). Studies have found that two brain areas, the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC), play important roles in treating OCD with this method.

For the PFC, research indicates that high-frequency stimulation is safe and can effectively reduce OCD symptoms, while also alleviating anxiety and depression.

Regarding the ACC, DBS is considered a promising therapy for severe OCD cases. This treatment has received approval for OCD under a special exemption, indicating expert confidence in its safety for this condition.

Overall, both types of brain stimulation are generally well-tolerated. Studies have not reported major safety concerns, suggesting these treatments could be safe options for people with OCD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cortical stimulation for treating Obsessive-Compulsive Disorder (OCD) because it offers a new way to target specific brain areas, like the Prefrontal Cortex (PFC) and Anterior Cingulate Cortex (ACC), that are linked to OCD symptoms. Unlike traditional deep brain stimulation, which is the current standard of care and involves more generalized brain stimulation, this approach aims for precision by focusing on these specific regions. This targeted method could potentially lead to more effective symptom relief with fewer side effects.

What evidence suggests that this trial's treatments could be effective for OCD?

Research has shown that stimulating certain brain areas might help reduce OCD symptoms. In this trial, participants will join different treatment arms. One arm targets the prefrontal cortex (PFC) with brain stimulation, which can lower anxiety and depression linked to OCD. Another arm focuses on the anterior cingulate cortex (ACC) using deep brain stimulation (DBS). This technique may improve OCD by altering brain communication. The ACC plays a crucial role in managing thoughts and actions, which can be challenging for those with OCD. Both PFC and ACC stimulation have shown promise in addressing the underlying causes of OCD symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

Andrew M Lee, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 22-75 with severe or extreme OCD (YBOCs ≥ 28) who haven't improved after cognitive behavior therapy, two types of antidepressants, and antipsychotics. Candidates should not have responded to TMS if available, must be able to consent, and have had OCD for at least 5 years.

Inclusion Criteria

My OCD is severe, with a YBOCs score of 28 or higher.

I haven't improved after treatment with two SSRIs, clomipramine, and antipsychotics.

I have tried cognitive behavior therapy without improvement.

Exclusion Criteria

Is pregnant

Allergies or known hypersensitivity to materials in the Activa systems (i.e. titanium, polyurethane, silicone, polyethermide, stainless steel)

Has hoarding as a primary subclassification of OCD according to DSM-4

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Biomarker Identification

Long-term monitoring of OCD and related psychiatric symptoms along with recordings of cortical and subcortical local field potentials (LFPs)

12 months

Multiple visits in outpatient office and home environment

Phase 2: Cortical Stimulation

Introduction of cortical stimulation at either the PFC or ACC/cingulum in addition to ALIC stimulation, with continued brain recordings and symptom ratings

12 months

Multiple visits in outpatient office and home environment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cortical Stimulation for ACC
• Cortical Stimulation for PFC
• Standard Therapeutic Deep Brain Stimulation

Trial Overview The study tests whether stimulating the prefrontal cortex (PFC) or anterior cingulate cortex (ACC), in addition to standard deep brain stimulation (DBS), can improve symptoms in OCD patients. It involves implanting electrodes and recording brain activity during different tasks over up to two years.

How Is the Trial Designed?

Group I: Prefrontal Cortex (PFC) Experimental Treatment 2 Interventions

The Prefrontal Cortex (PFC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the PFC.

Group II: Anterior Cingulate Cortex (ACC) Experimental Treatment 2 Interventions

The Anterior Cingulate Cortex (ACC) treatment group will be have an implant bilaterally at the HDE-approved ALIC site and the ACC.

Cortical Stimulation for ACC is already approved in United States, European Union for the following indications:

Approved in United States as Deep Brain Stimulation (DBS) for:

• Obsessive Compulsive Disorder (OCD)
• Parkinson's disease
• Other movement disorders
• Epilepsy

Approved in European Union as Deep Brain Stimulation (DBS) for:

• Obsessive Compulsive Disorder (OCD)
• Parkinson's disease
• Other movement disorders
• Epilepsy

Who Is Running the Clinical Trial?

Andrew Moses Lee, MD, PhD

Lead Sponsor

Trials

2

Recruited

30+

Published Research Related to This Trial

Deep brain stimulation (DBS) is a novel treatment for severe obsessive-compulsive disorder (OCD) that directly modulates brain activity, offering a different mechanism of action compared to traditional therapies like medication and psychotherapy.

The effectiveness of DBS is evaluated through an interactive process between clinicians and patients, where improvements are seen as increased patient engagement and openness to therapeutic activities, suggesting that DBS can enhance the potential for additional cognitive behavioral therapy (CBT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise. van Westen, M., Rietveld, E., Denys, D.[2023]

In a study of 70 patients receiving deep brain stimulation (DBS) for treatment-refractory OCD, insight into the illness was the only significant predictor of treatment response, with an 84.4% positive predictive value.

Demographic factors like late-onset OCD and comorbid personality disorders influenced symptom changes but were not reliable enough to predict DBS outcomes, suggesting that clinical characteristics should not be used to exclude patients from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Response to vALIC Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder. Graat, I., Mocking, RJT., de Koning, P., et al.[2021]

Deep brain stimulation (DBS) targeting the internal capsule (IC) significantly reduced excessive grooming behaviors in Sapap3 mutant mice, a model for obsessive-compulsive disorder (OCD), indicating its potential efficacy in treating OCD symptoms.

While both IC and dorsal part of the ventral striatum (dVS) stimulation modulated prefrontal cortical activity, IC-DBS was more effective and also increased locomotion, suggesting a need to balance therapeutic effects with potential side effects in treatment.

NCBI (Pubmed)

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. Pinhal, CM., van den Boom, BJG., Santana-Kragelund, F., et al.[2019]

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]

This study will evaluate the safety and efficacy of combined deep brain stimulation (DBS) targeting the anterior limb of the internal capsule (ALIC) and nucleus accumbens (NAcc) in 64 patients with treatment-refractory obsessive-compulsive disorder (OCD).

The trial includes a three-month double-blind phase followed by a three-month open-label phase, aiming to compare treatment response rates and adverse events between active and sham stimulation groups, with outcomes measured using standardized OCD and depression scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Deep Brain Stimulation of Combined Anterior Limb of Internal Capsule and Nucleus Accumbens (ALIC/NAcc-DBS) for Treatment-Refractory Obsessive-Compulsive Disorder: Protocol of a Multicenter, Randomized, and Double-Blinded Study. Xu, T., Gao, Y., Li, B., et al.[2022]

In a review of 20 studies involving 170 patients with refractory OCD, anterior capsulotomy (AC) resulted in a greater reduction in obsessive-compulsive symptoms (51% decrease in YBOCS score) compared to deep brain stimulation (DBS) (40% decrease), indicating AC may be more effective for some patients.

Patients who underwent AC were 9% more likely to achieve remission compared to those treated with DBS, suggesting that while DBS is a promising therapy, AC remains a highly effective option for treating severe OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature. Pepper, J., Hariz, M., Zrinzo, L.[2022]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAcc) shows promise as a treatment for patients with treatment-resistant major depression (MD) and obsessive-compulsive disorder (OCD), particularly due to its favorable safety profile and limited side effects.

This case study reports the successful use of bilateral NAcc-DBS in a 27-year-old male patient, marking the first instance of DBS treatment for a psychiatric disorder in Turkey, highlighting its potential as a novel intervention in challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major Depression and Obsessive-compulsive Disorder Treated with Deep Brain Stimulation of Bilateral Nucleus Accumbens: The First Case of Turkey. Aydın, S., Canaz, H., Topcular, B., et al.[2020]

In a study of 16 OCD patients who underwent deep brain stimulation (DBS) for at least one year, stopping DBS for just one week led to a significant increase in obsessive-compulsive symptoms, anxiety, and depression, with scores rising by 50%, 80%, and 83% respectively.

The cessation of DBS also resulted in a noticeable decline in quality of life, reverting to levels similar to those before surgery, indicating that stopping DBS can lead to a rapid relapse and rebound of psychiatric symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rebound of affective symptoms following acute cessation of deep brain stimulation in obsessive-compulsive disorder. Ooms, P., Blankers, M., Figee, M., et al.[2018]

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) targeting the anterior limb of the internal capsule and nucleus accumbens significantly reduced OCD symptoms by an average of 33%, with 40% of patients achieving full response over a 1-year period in a study involving 20 patients.

The treatment was found to be safe, with only minor adverse events reported; however, 35% of patients experienced increased anxiety and anhedonia after stopping stimulation, highlighting the need for careful monitoring of withdrawal effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label trial of anterior limb of internal capsule-nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained. Huys, D., Kohl, S., Baldermann, JC., et al.[2020]

A prospective study involving 16 subjects demonstrated that deep brain stimulation (DBS) of the nucleus accumbens is effective and safe for treating severe, medication-refractory obsessive-compulsive disorder (OCD).

The study provided evidence that the efficacy of DBS is genuine, as it included comparisons between sham and active stimulation, and offered insights into how DBS may interact with the brain, enhancing our understanding of OCD's underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing deep brain stimulation for obsessive-compulsive disorder. Burdick, AP., Foote, KD.[2011]

Citations

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Deep Brain Stimulation for Obsessive Compulsive Disorder Deep brain stimulation (DBS) is thought to alleviate OCD symptoms by modulating underlying disturbances in normal cortico-striato-thalamo-cortical (CSTC) ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949669123000106

The role of the dorsal anterior cingulate cortex in obsessive ... The dorsal anterior cingulate cortex (dACC) plays an important role in cognitive control and is therefore hypothesized to contribute to the pathogenesis of OCD.

3. clinicaltrial.be clinicaltrial.be/en/details/41888?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Cortical Stimulation to Treat Obsessive Compulsive Disord... This new study will utilize the Medtronic Percept, which is currently is approved for treating OCD under the Humanitarian Device Exemption (HDE) ...

4. thejns.org thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/8/18/article-CASE24289.xml

Effective deep brain stimulation for obsessive-compulsive ... The authors demonstrate that DBS can be utilized even after a lesioning procedure in nominally the same target (ventral portion of the anterior limb of the ...

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Cortical Stimulation to Treat Obsessive Compulsive Disorder The purpose of this study is to identify abnormal brain signals associated with Obsessive Compulsive Disorder (OCD) and psychiatric symptoms ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474989/

Deep brain stimulation for obsessive-compulsive disorder The results confirm that deep brain stimulation (DBS) is a promising therapy for patients with severe and resistant forms of the disorder.

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Clinical and electrophysiological outcomes of deep TMS ... Deep TMS over the mPFC and ACC was examined as a novel treatment for OCD. Clinical and EEG measurements were conducted before and after 5 weeks of treatment.

8. dbsjournal.com dbsjournal.com/article/S2949-6691(23)00010-6/fulltext

The role of the dorsal anterior cingulate cortex in ... The dorsal anterior cingulate cortex (dACC) plays an important role in cognitive control and is therefore hypothesized to contribute to the pathogenesis of OCD.