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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new surgical treatment called Deep Brain Stimulation (DBS) for individuals with severe and persistent PTSD (Post-Traumatic Stress Disorder) that hasn't improved with other treatments. DBS involves implanting electrodes in the brain to help manage PTSD symptoms. The study aims to determine if DBS can alter the brain activity associated with PTSD and enhance patients' quality of life. Individuals with stable PTSD for at least a year, without relief from medications or therapy, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

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 prior data suggests that Deep Brain Stimulation is safe for treating PTSD?

Research has shown that deep brain stimulation (DBS) is an experimental treatment under study for PTSD. In a study with veterans, researchers used DBS for several years without causing seizures or other major mental health issues. Another study found that DBS could be safe and effective, with participants experiencing significant reductions in PTSD symptoms.

DBS has also been studied for other conditions, such as depression, focusing on a brain area involved in mood regulation. This suggests the procedure is generally well-tolerated.

While DBS is still in early testing for PTSD, these findings offer some reassurance about its safety in humans. However, because this is an early-phase trial, there is limited safety data specific to PTSD. Participants should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for PTSD?

Researchers are excited about deep brain stimulation (DBS) for PTSD because it offers a novel approach compared to the usual treatments like therapy and medication. Unlike traditional methods that address symptoms through talk therapy or drugs affecting brain chemicals, DBS directly targets specific brain areas involved in stress and fear response. This precision could lead to faster and more effective relief of PTSD symptoms. Additionally, the trial's use of a closed-loop system, which adjusts stimulation in real-time based on brain activity, represents a futuristic step in personalized medicine, potentially increasing treatment efficacy and reducing side effects.

What evidence suggests that Deep Brain Stimulation could be an effective treatment for PTSD?

Research has shown that deep brain stimulation (DBS), one of the treatments under study in this trial, could be a promising option for PTSD. In some studies, patients experienced significant symptom reductions, with PTSD severity decreasing by up to 79%. Another study reported a 56% decrease in PTSD scores, highlighting the procedure's potential effectiveness. DBS targets specific brain areas involved in mood and anxiety control, such as the subgenual cingulate, which has been successfully used in treating depression. Although still under investigation, these results suggest DBS might offer hope for those with PTSD that hasn't responded to other treatments. ^{1 2 4 5 6}

Who Is on the Research Team?

Nir Lipsman, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5789349/

DBS in Treatment of Post-Traumatic Stress Disorder - PMC Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725018324

Patient-centered insights into deep brain stimulation ... At this time, two patients were classified as responders (>50 % improvement), one as a partial responder (30–49 % improvement), and the ...

3. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.neuropsych.20250055

Deep Brain Stimulation in Chronic Posttraumatic Stress ... Both BLa patients had total reductions in CAPS scores of 79% and 44% at 5 and 8 years, respectively, after their initial DBS implantation. No ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03416894

Deep Brain Stimulation for Treatment Refractory PTSD In psychotherapy-based studies, over 30% of patients that completed a full course of treatment continue to meet criteria for PTSD. Response rates to treatment ...

5. science.org science.org/doi/10.1126/sciadv.adc9970

Deep brain stimulation of the subgenual cingulum and ... We show that the procedure is safe and potentially effective (56% reduction in Clinical Administered PTSD Scale scores). Posttreatment imaging ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0022395624002644

Deep brain stimulation of the amygdala for treatment ... Two veterans with severe combat TR-PTSD received amygdala DBS for 9 and 5.5 years. Stimulation resulted in no seizures, neuropsychological or psychiatric ...