Deep Brain Stimulation for Post-Traumatic Stress Disorder

Overseen By Anusha Baskaran, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Psychosis, Mania, Neurologic disease, others

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

Compensation: Varies

Number of Visits: 7

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Treatment refractory PTSD is a chronic and debilitating psychiatric disorder associated with high morbidity. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions in the last half century, little progress has been made in altering the natural history of the condition or its outcome. This study would be the first exploration of a surgical therapy for refractory PTSD. The subgenual cingulate plays a role in mechanisms of this disorder and has been successfully targeted with DBS for the treatment of depression The study will proceed in three stages: pre-operative, operative and post-operative. In the pre-operative stage, consent will be obtained and patients will be scheduled for additional investigations, including neuroimaging (MRI), neuropsychological testing, psychophysiological testing, and a pre-operative assessment by the anesthesia service. In the operative stage, patient will have a stereotactic frame attached directly to their skull. The patient will then undergo a computed tomography (CT) scan with the frame in place, followed by transport directly to the operating room. A skin incision will be made and two burr holes drilled through the skull. After target identification DBS electrodes will be inserted and fixed in place. Patients will be then immediately anesthetized (general anesthesia) for the next step of the surgery. This will involve implanting an internal pulse generator (IPG) under the collarbone and connecting it to the DBS electrodes. During the post-operative phase, patients will return to the clinic 2 weeks after surgery.DBS programming visits will happen biweekly for three months, and monthly thereafter.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study involves surgical intervention, it's best to discuss your current medications with the study team to ensure safety and compatibility with the trial.

What data supports the effectiveness of the treatment Deep Brain Stimulation for Post-Traumatic Stress Disorder?

Deep Brain Stimulation (DBS) has shown potential effectiveness in reducing PTSD symptoms, with one study reporting a 55% reduction in PTSD severity scores. Additionally, DBS has been used successfully for other conditions like depression and obsessive-compulsive disorder, suggesting it may help with PTSD as well. ^{1 2 3 4 5}

Is Deep Brain Stimulation generally safe for humans?

Deep Brain Stimulation (DBS) is generally considered safe, but it can have surgical and hardware-related complications. These complications can affect quality of life and may require management, but they are typically manageable and do not outweigh the potential benefits for many patients. ^{1 6 7 8 9}

How is deep brain stimulation different from other treatments for PTSD?

Deep brain stimulation (DBS) is unique because it involves implanting electrodes in specific brain areas to modulate brain activity, offering hope for PTSD patients who do not respond to conventional treatments. Unlike medications or talk therapy, DBS directly targets brain circuits involved in PTSD, potentially reducing symptoms by altering brain function. ^{1 2 3 4 5}

Research Team

Nir Lipsman, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for individuals with severe PTSD that hasn't improved after trying other treatments. Participants must be eligible for surgery, willing to undergo various pre-operative tests like MRI and CT scans, and commit to regular follow-up visits post-surgery.

Inclusion Criteria

I have had PTSD for at least one year.

Ability to provide informed consent and comply with all testing, follow-ups and study appointments and protocols

My condition didn't improve after trying four different treatments including medication and therapy.

Exclusion Criteria

Likely to relocate or move out of the country during the study's duration

Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine

Any contraindication to MRI or PET scanning

Timeline

Pre-operative

Consent obtained and patients scheduled for additional investigations, including neuroimaging, neuropsychological testing, psychophysiological testing, and a pre-operative assessment by the anesthesia service

2-4 weeks

1 visit (in-person)

Operative

Stereotactic frame attachment, CT scan, DBS electrode insertion, and IPG implantation

1 day

1 visit (in-person)

Post-operative

DBS programming visits biweekly for three months, and monthly thereafter

60 weeks

Biweekly visits for 3 months, then monthly

Open label

Open label phase from surgery until postoperative week 24

24 weeks

Double-blinded 'on/off'

Double-blinded 'on/off' phase from postoperative week 25 to 33

8 weeks

Prolonged exposure therapy

Prolonged exposure therapy from postoperative week 34 to 44

10 weeks

Closed-loop DBS

Closed-loop DBS from postoperative week 45 to 60

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 2 weeks until the 8 weeks mark, every 4 weeks until 6 month mark and every two months until the 2 year mark

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The study is testing Deep Brain Stimulation (DBS) as a surgical treatment for refractory PTSD by targeting the subgenual cingulate. It includes three stages: pre-operative assessments, the surgical procedure of implanting electrodes and an internal pulse generator, followed by biweekly then monthly programming visits.

Participant Groups

Group I: Prolonged exposure therapy Experimental Treatment 1 Intervention

Prolonged exposure therapy (from postoperative week 34to 44)

Group II: Open label Experimental Treatment 1 Intervention

1) Open label phase (from surgery until postoperative week 24)

Group III: Closed-loop DBS Experimental Treatment 1 Intervention

Closed-loop DBS (from postoperative week 45 to 60).

Group IV: Double-blinded "on/off" phase Placebo Group 1 Intervention

Double-blinded "on/off" phase (from postoperative week 25 to 33)

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?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

Deep brain stimulation (DBS) has been explored as a treatment for PTSD, particularly in combat veterans, with promising results observed in animal models targeting specific brain areas like the medial prefrontal cortex and amygdala.

In clinical reports involving 3 patients, all showed varying degrees of improvement after receiving DBS, indicating potential efficacy, but the treatment remains investigational due to ethical concerns and challenges in recruitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Meeres, J., Hariz, M.[2022]

Deep brain stimulation (DBS) targeting the subgenual cingulum and uncinate fasciculus in four PTSD patients was found to be safe and showed a promising 55% reduction in PTSD symptoms as measured by the Clinical Administered PTSD Scale.

Neuroimaging revealed changes in brain activity related to PTSD, and a significant reduction in skin conductance responses during fear recall assessments after DBS suggests that this treatment may effectively alter physiological responses associated with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subgenual cingulum and uncinate fasciculus for the treatment of posttraumatic stress disorder. Hamani, C., Davidson, B., Corchs, F., et al.[2022]

Deep brain stimulation (DBS) is being explored as a potential treatment for patients with post-traumatic stress disorder (PTSD) who do not respond to traditional pharmacological therapies.

Current research, including both preclinical and clinical studies, suggests that DBS may offer hope for treatment-refractory PTSD patients, although it is still in the early stages of investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DBS in Treatment of Post-Traumatic Stress Disorder. Lavano, A., Guzzi, G., Della Torre, A., et al.[2020]

Deep brain stimulation (DBS) is an effective and safe treatment for therapy-refractory obsessive-compulsive disorder (OCD), showing rapid improvements in mood and anxiety symptoms.

DBS has also shown promising results in treating refractory depression and Tourette syndrome, but more research is needed to explore its efficacy for other psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation in psychiatry]. Figee, M., Bervoets, C., Denys, D.[2018]

This study outlines a Phase I pilot trial investigating the safety and efficacy of deep brain stimulation (DBS) targeting the basolateral amygdala in six combat veterans with severe, treatment-resistant PTSD, with a primary goal of achieving a 30% reduction in PTSD symptoms as measured by the Clinician Administered PTSD Scale (CAPS).

The trial design includes rigorous safety monitoring and assessments of psychiatric and neurological symptoms, aiming to gather valuable data that could inform future studies on DBS for PTSD in both veterans and non-veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation. Koek, RJ., Langevin, JP., Krahl, SE., et al.[2023]

In a study of 200 patients undergoing deep brain stimulation (DBS) procedures over a follow-up period of approximately 43 months, 20% experienced surgical or hardware-related adverse events (AEs), but all resolved without permanent effects.

The most common AEs were surgical site infections (9.95%) and wire tethering (2.49%), indicating that while AEs can occur, major complications requiring further surgery are rare, highlighting the overall safety of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. Bouwens van der Vlis, TAM., van de Veerdonk, MMGH., Ackermans, L., et al.[2022]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

This study presents the first case of safely administering electroconvulsive therapy (ECT) to a patient with deep brain stimulation (DBS) by temporarily interrupting DBS only during the ECT sessions.

Previous reports indicated no adverse events when DBS was withheld for the entire ECT course, but this case suggests that short interruptions during ECT may be a safe approach, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. Ducharme, S., Flaherty, AW., Seiner, SJ., et al.[2011]

A systematic review of 96 studies found that the most common complications from Deep Brain Stimulation (DBS) procedures include infections (5.12% of patients) and lead migration (1.60%), highlighting the importance of monitoring for these issues post-surgery.

Patients with conditions like dystonia and off-label indications such as Tourette's syndrome are at a higher risk for hardware-related complications, suggesting that these patients should receive thorough pre-surgical counseling and close follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? Jitkritsadakul, O., Bhidayasiri, R., Kalia, SK., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. [2022]

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

Deep brain stimulation of the subgenual cingulum and uncinate fasciculus for the treatment of posttraumatic stress disorder. [2022]

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

DBS in Treatment of Post-Traumatic Stress Disorder. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation in psychiatry]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation. [2023]

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

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience. [2022]

7. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

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

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. [2011]

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

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? [2022]