Deep Brain Stimulation for Obsessive-Compulsive Disorder

Overseen By Tash Mupambo

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nader Pouratian

Must be taking: Serotonin transport inhibitors

Disqualifiers: Severe MDD, Psychotic disorder, PTSD, 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: 9

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to learn if deep brain stimulation (DBS) works to treat refractory obsessive-compulsive disorder (OCD). The main questions it aims to answer are: * Assess the effects of the anteromedial sub-thalamic nucleus (amSTN)stimulation on obsessive/compulsive symptoms. * Map the amSTN using neuronal responses \[single unit and local field potentials (LFP) recordings\] at rest and under high frequency stimulation during surgery. * Record chronic brain activity with the implanted pulse generator and look for neuronal signatures correlated with symptom severity. Researchers will compare active deep brain stimulation to a placebo (sham stimulation) to see if DBS works to treat refractory OCD. Participants will: * Undergo surgery for the implantation of a deep brain stimulation device * Follow-up visits every three weeks with study staff * 6 month follow-up for the next 2-3 years after first year of study participation is complete

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves deep brain stimulation for severe OCD that hasn't improved with medication, it's possible you may continue your current treatment. Please consult with the study team for specific guidance.

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 infections, bleeding, and seizures, but these are relatively rare. ^{1 2 3 4 5}

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 do not respond to other treatments, offering a new option for those who have exhausted conventional therapies. ^{6 7 8 9 10}

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 has been used successfully for other conditions like Parkinson's disease, and its application to OCD has been approved by the FDA due to its effectiveness. ^{7 10 11 12 13}

Who Is on the Research Team?

Nader Pouratian

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with severe Obsessive-Compulsive Disorder (OCD) that hasn't improved with standard treatments. Participants will undergo surgery to implant a deep brain stimulation device and must commit to follow-up visits every three weeks, plus long-term check-ups for 2-3 years after the first year.

Inclusion Criteria

I am between 22 and 75 years old.

Severe OCD assessed by the Yale-Brown Obsessive-Compulsive Scale (YBOCS) with a score of more than 27

I have been diagnosed with obsessive-compulsive disorder.

Exclusion Criteria

Significant suicidal risk (Hamilton Depression scale item 3 (suicide) >2)

History of substance or alcohol dependence or abuse in the preceding 12 months

I have a primary psychotic disorder, PTSD, or an eating disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Participants undergo surgery for the implantation of a deep brain stimulation device and begin initial treatment phase

16 weeks

Intra-operative recordings and initial follow-up visits

Cross-over Treatment

Participants are randomized to either sham or therapeutic stimulation for 16 weeks, then cross-over to the other condition

32 weeks

Formal psychiatric assessments every 3 weeks

Open-label Extension

All participants transition to an open-label stimulation phase for chronic therapy

Long-term

Assessments every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months for 2-3 years

Follow-up visits every three weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The study tests if activating certain brain areas with Medtronic Percept Deep Brain Stimulation Therapy improves OCD symptoms compared to sham (fake) stimulation. It also involves mapping brain activity related to symptom severity during and after surgery.

How Is the Trial Designed?

Group I: Therapeutic stimulation, then Sham Control stimulation Experimental Treatment 2 Interventions

Subjects randomized to this arm are initially "ON" DBS prior to the open label period for 16 weeks and then "OFF" DBS for the next 16 weeks. This is followed by an open-label stimulation period.

Group II: Therapeutic stimulation Experimental Treatment 1 Intervention

All participants will transition to an open label stimulation phase for chronic therapy after the cross-over portion of this trial

Group III: Sham Control stimulation, then Therapeutic stimulation Experimental Treatment 2 Interventions

Subject randomized to this arm are initially "OFF" DBS (Deep Brain Stimulation) prior to the open label period for 16 weeks and then "ON" DBS for the next 16 weeks. This is then followed by an open-label period of DBS stimulation.

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?

Nader Pouratian

Lead Sponsor

Trials

4

Recruited

20+

Published Research Related to This Trial

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) 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) 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]

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 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]

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]

Citations

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

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

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

Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design. [2022]

3. 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]

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

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

12. 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]

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

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