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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to identify abnormal brain signals associated with Obsessive Compulsive Disorder (OCD) and psychiatric symptoms and to investigate novel therapeutic stimulation sites. While treating OCD with standard deep brain stimulation (DBS) therapy, the investigators will also monitor the activity of the anterior cingulate and prefrontal cortex, a region known be involved with OCD, decision making, and emotion regulation, and the investigators will identify abnormal activity corresponding to the severity of a patient's OCD. The investigators will also investigate whether it is possible for stimulation delivered to these parts of the brain can improve OCD symptoms. These investigations have the potential to aid in the development of improved forms of DBS that can better target abnormal OCD brain signatures in the future. The investigators will implant a cortical electrode in addition to the ALIC DBS electrode and connect these to an implantable pulse generator that care store field potential data (Medtronic Percept). The decision whether the lead is placed in the prefrontal or cingulate cortex bilaterally will be based upon considerations of the surgical risks for a particular patient based upon their anatomy and the required surgical approach. At multiple time points post-implantation up to 2 years, in our clinic or patient's homes, cortical and subcortical signals will be recorded. Data will be collected while patient are resting or engaged in symptom provocation tasks, emotional/cognitive tasks while cortical stimulation is on and off. In addition to brain signal recordings, symptoms will be assessed using validated questionnaires and tasks to allow identification of neurophysiological correlates of OCD symptoms.

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 data supports the effectiveness of this treatment for obsessive-compulsive disorder?

Research shows that deep brain stimulation (DBS) is an effective treatment for severe obsessive-compulsive disorder (OCD) that doesn't respond to other therapies. It works by directly changing brain activity in specific areas, offering a new way to manage symptoms compared to traditional treatments like therapy or medication. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for treating obsessive-compulsive disorder (OCD)?

Deep brain stimulation (DBS) for OCD has been studied for safety, and while some serious adverse events (AEs) can occur, most are mild or moderate and resolve with adjustments. In a study of 30 patients, all experienced AEs, but the majority were mild or moderate, and the potential benefits of DBS were found to outweigh the risks in treatment-resistant cases. ^{3 6 7 8 9}

How is the treatment 'Brain Stimulation for Obsessive-Compulsive Disorder' different from other treatments for OCD?

This treatment uses deep brain stimulation (DBS), which involves implanting electrodes in specific brain areas to directly change brain activity, offering a unique approach compared to traditional therapies like medication or psychotherapy. It is particularly used for severe cases of OCD that do not respond to other treatments. ^{2 3 4 10 11}

Research Team

Andrew M Lee, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2019]

2. England 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. [2020]

3. India 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. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effective Deep Brain Stimulation for Obsessive-Compulsive Disorder Requires Clinical Expertise. [2023]

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

Rebound of affective symptoms following acute cessation of deep brain stimulation in obsessive-compulsive disorder. [2018]

6. Switzerland 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. [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. 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]

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

Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature. [2022]

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

Predicting Response to vALIC Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder. [2021]

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

Advancing deep brain stimulation for obsessive-compulsive disorder. [2011]