Deep Brain Stimulation for Obsessive-Compulsive Disorder

Overseen By Gen Basich-Pease, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Andrew Moses Lee, MD, PhD

Must be taking: SSRIs, Antipsychotics, Clomipramine

Disqualifiers: Personality disorder, Bipolar, Substance abuse, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a double-blinded, randomized, crossover study design for SEEG-guided 4-lead DBS for treatment-refractory OCD, followed by open label stimulation for an additional 6 months. The study will be conducted in 3 stages: Stage 1 will consist of SEEG brain mapping and optimization of stimulation parameters. Stage 2 will consist of 4-lead DBS surgery with bilateral IPGs and further optimization of stimulation parameters. Stage 3 will be randomized, crossover treatment, followed by open label treatment.

Will I have to stop taking my current medications?

The trial requires participants to stay on the same daily dose of any psychotropic medications for at least 8 weeks before joining and throughout the study. So, you won't have to stop your current medications, but you must maintain the same dosage.

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

Deep Brain Stimulation (DBS) has shown promising results for people with severe OCD who do not respond to other treatments, with about 60% of patients experiencing improvement. It is a procedure that has been used successfully for other conditions like Parkinson's disease, and it has been approved by the FDA for OCD treatment. ^{1 2 3 4 5}

Is Deep Brain Stimulation generally safe for humans?

Deep Brain Stimulation (DBS) has been used for various conditions, including Parkinson's disease and obsessive-compulsive disorder (OCD). While some serious side effects can occur, most adverse events are mild or moderate and often resolve with adjustments to the stimulation settings. Common issues include temporary anxiety or mood changes, and rare complications like infections or bleeding. ^{6 7 8 9 10}

How is deep brain stimulation different from other treatments for obsessive-compulsive disorder?

Deep brain stimulation (DBS) is unique because it involves implanting electrodes in specific brain areas to directly change brain activity, unlike traditional treatments like therapy or medication. It is used for severe cases of OCD that don't respond to other treatments, offering a new option for those who are treatment-resistant. ^{3 5 11 12 13}

Research Team

Andrew Krystal, MD, MS

Principal Investigator

University of California, San Francisco

A Moses Lee, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for individuals with severe Obsessive-Compulsive Disorder (OCD) that hasn't improved with standard treatments. Participants must be suitable for brain surgery and willing to undergo detailed brain mapping, as well as a follow-up period involving both blinded and open label treatment phases.

Inclusion Criteria

I have tried at least one antipsychotic medication to improve my condition.

Willingness and ability to remain on the same daily dose of any and all scheduled psychotropic medication(s) for at least 8 weeks prior to study enrollment and for the duration of the trial, in the opinion of the Principal Investigator

Time-consuming obsessions and compulsions that take more than one hour a day or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

Exclusion Criteria

Current participation in other research that may potentially interfere with DBS study objectives or with the ability to follow the timeline of this study, as determined by the Principal Investigator

Diagnosed, according to the Mini International Neuropsychiatric Interview (MINI), as suffering from any other primary psychiatric diagnosis defined in the DSM-5, including Hoarding Disorder

I have been diagnosed with a specific mental health condition like bipolar disorder or an eating disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SEEG Brain Mapping and Optimization

Implantation of SEEG depth electrodes and extensive stimulation mapping to identify anatomical sites and stimulation parameters that improve symptoms.

12 days

DBS Surgery and Optimization

Placement of 4 DBS leads using the Medtronic Percept Implantable Pulse Generator system and programming to find optimal stimulation parameters.

18 months

Randomized Crossover Treatment

Randomized, controlled, crossover trial to assess the safety, feasibility, and initial efficacy of SEEG-guided DBS.

12 weeks

Open-label Treatment

Open label stimulation for an additional 6 months following the crossover treatment.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 years

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The study tests Deep Brain Stimulation (DBS), where electrodes are placed in specific brain areas to control OCD symptoms. It's a three-stage process including initial brain mapping, surgical implantation of stimulation devices, and a randomized crossover phase followed by an open label treatment.

Participant Groups

Group I: ON-OFF (Stimulation-Sham) Experimental Treatment 1 Intervention

Patients in the ON-OFF arm will first be treated for up to 12 weeks with the parameters identified during the DBS optimization phase until the washout period.

Group II: OFF-ON (Sham-Stimulation) Experimental Treatment 1 Intervention

Patients in the OFF-ON will have their devices turned off and will not have their device switched on (activated) until the crossover point.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

Andrew Moses Lee, MD, PhD

Lead Sponsor

Trials

2

Recruited

30+

Findings from Research

Deep brain stimulation (DBS) for severe treatment-refractory obsessive-compulsive disorder (OCD) showed a significant long-term reduction in OCD symptoms by 39% over an average follow-up of 6.8 years, with half of the patients experiencing a substantial response.

DBS also led to significant improvements in anxiety and depression symptoms, quality of life, and overall functioning, while the unemployment rate decreased from 78% to 58%, indicating enhanced well-being despite some long-term adverse effects like cognitive complaints and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder. Graat, I., Mocking, R., Figee, M., et al.[2021]

Deep brain stimulation (DBS) has been effectively used for treating severe, refractory obsessive-compulsive disorder (OCD), building on decades of experience with neurosurgical interventions.

The therapy received Humanitarian Device Exemption (HDE) approval from the FDA in 2009 due to promising results, indicating its potential as a viable treatment option for patients with OCD who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for obsessive-compulsive disorder. Arya, S., Filkowski, MM., Nanda, P., et al.[2019]

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]

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) in the bed nucleus of stria terminalis (BNST) showed a significant response in 60% of the 10 patients with severe, treatment-resistant OCD, with an average symptom reduction of 53% as measured by the YBOCS scale.

The treatment not only reduced OCD symptoms but also improved depressive symptoms, global functioning, and quality of life, indicating that DBS could be a promising option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions. Abdelnaim, MA., Lang-Hambauer, V., Hebel, T., et al.[2023]

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]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

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) can lead to significant psychiatric side effects, particularly when electrodes are implanted in the subthalamic nucleus, which is associated with increased risks of depression and suicidal thoughts.

Higher voltage settings during DBS are linked to more severe depressive symptoms, highlighting the need for careful management of stimulation parameters to minimize adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation-induced side effects after deep brain stimulation - a systematic review. Zarzycki, MZ., Domitrz, I.[2022]

In a study of 21 patients with severe OCD or MDD undergoing deep brain stimulation (DBS) in the ventral striatum, no significant cognitive declines were observed after an average of 8.91 months of stimulation.

Patients showed significant improvements in verbal memory, suggesting that DBS may enhance cognitive functions without negatively impacting overall mental health, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological outcome after deep brain stimulation in the ventral capsule/ventral striatum for highly refractory obsessive-compulsive disorder or major depression. Kubu, CS., Malone, DA., Chelune, G., et al.[2013]

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]

References

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

Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder. [2021]

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

Deep brain stimulation for obsessive-compulsive disorder. [2019]

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. France pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment resistant obsessive compulsive disorder; an observational study with ten patients under real-life conditions. [2023]

6. 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]

7. 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]

8. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

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

10. England pubmed.ncbi.nlm.nih.gov

Stimulation-induced side effects after deep brain stimulation - a systematic review. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Neuropsychological outcome after deep brain stimulation in the ventral capsule/ventral striatum for highly refractory obsessive-compulsive disorder or major depression. [2013]

12. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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