Deep Brain Reorienting for Post-Traumatic Stress Disorder

Overseen By Suzy - Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Narcotics

Disqualifiers: Neurological disorder, Bipolar, Psychotic, others

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

Compensation: Varies

Number of Visits: 10

Duration: 8 weeks

214 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will evaluate the efficacy of a therapeutic treatment, Deep Brain Reorienting (DBR), for PTSD (Post-traumatic Stress Disorder). Participants will be randomized to either the DBR treatment, or wait-list condition.

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, if you are using extensive narcotics or have untreated medical illnesses, you may not be eligible to participate.

Is Deep Brain Reorienting (DBR) safe for humans?

There is limited data on the safety of Deep Brain Reorienting (DBR) specifically, but related treatments like Deep Brain Stimulation (DBS) have been shown to be safe in small studies for conditions like PTSD, with some human data supporting their potential safety. ^{1 2 3 4 5}

How is the treatment Deep Brain Reorienting (DBR) different from other treatments for PTSD?

Deep Brain Reorienting (DBR) is unique because it targets the brainstem-level processes that occur during a traumatic event, which is different from other treatments that often focus on symptoms or higher brain functions. This approach is based on advanced neuroscientific insights and aims to address the root neurophysiological sequence of trauma, potentially offering a new option for those who do not respond to existing therapies. ^{3 6 7 8 9}

What data supports the effectiveness of the treatment Deep Brain Reorienting (DBR) for post-traumatic stress disorder (PTSD)?

The research suggests that Deep Brain Reorienting (DBR) is being explored as a potential treatment for PTSD, especially since current treatments have high non-response and drop-out rates. While specific effectiveness data for DBR is not provided, similar treatments like Deep Brain Stimulation (DBS) have shown promise in reducing PTSD symptoms, indicating that targeting brain circuits can be beneficial. ^{2 3 4 10 11}

Who Is on the Research Team?

Ruth A Lanius, MD, PhD

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-65 with PTSD who might gain from short-term trauma therapy. It's not for those with implants or conditions unsafe for high-strength fMRI, significant head injuries, untreated major illnesses, neurological disorders, extensive current counseling (like exposure therapy), severe mental distress unsuitable for brief treatment, developmental disorders, bipolar or psychotic history, or recent substance abuse.

Inclusion Criteria

English speaking

I have been diagnosed with PTSD by this study's assessment.

I might benefit from short-term therapy for trauma.

Exclusion Criteria

History of bipolar disorder

I have mental distress that may not improve quickly with short-term therapy.

Individuals with any implants, conditions, etc. that do not comply with 7-Tesla (7T) fMRI research safety standards (e.g., certain implants, pregnancy)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8 weekly sessions of Deep Brain Reorienting (DBR) treatment

8 weeks

8 visits (in-person or virtual)

Wait-list

Participants in the wait-list condition receive no intervention for approximately 8 weeks

8 weeks

Follow-up

Participants are monitored for changes in PTSD symptoms post-treatment

3 months

2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• DBR

Trial Overview The study tests Deep Brain Reorienting (DBR) as a treatment for PTSD. Participants will be randomly assigned to either receive DBR therapy or placed on a wait-list as part of the control group to compare outcomes between the two sets.

How Is the Trial Designed?

Group I: DBR Condition Experimental Treatment 1 Intervention

Involves 8 weekly sessions of DBR treatment.

Group II: Wait-list Condition Active Control 1 Intervention

No intervention for approximately 8 weeks.

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Deep Brain Reorienting (DBR) significantly reduced PTSD symptoms in a clinical trial with 54 participants, showing a 36.6% reduction post-treatment and a 48.6% reduction at a three-month follow-up, compared to no significant changes in the waitlist control group.

After treatment with DBR, nearly half of the participants (48.3% post-treatment and 52.0% at follow-up) no longer met the criteria for PTSD, indicating its potential efficacy as a well-tolerated intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder. Kearney, BE., Corrigan, FM., Frewen, PA., 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]

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) 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]

Soldiers with PTSD showed reduced cortical thickness in the frontal and temporal lobes, indicating significant structural brain changes associated with the disorder.

The study also found decreased volumes in the caudate and right hippocampus, along with enlargement in certain cerebellar lobules, suggesting that advanced neuroimaging can help in diagnosing and understanding PTSD's effects on brain anatomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroanatomical features in soldiers with post-traumatic stress disorder. Sussman, D., Pang, EW., Jetly, R., et al.[2019]

Closed Loop Deep Brain Stimulation (CLDBS) offers a promising approach for treating psychiatric disorders by allowing real-time modulation of brain circuits based on individual physiological biomarkers, unlike Open Loop DBS which delivers fixed stimulation.

CLDBS could potentially improve conditions like PTSD and addiction by utilizing biomarkers such as skin conductance and neurotransmitter levels, paving the way for more effective treatments for previously resistant psychiatric diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms. Bina, RW., Langevin, JP.[2020]

Deep brain stimulation (DBS) targeting the infralimbic cortex significantly improved anxiety-like behaviors and extinction deficits in rats with weak extinction responses after fear conditioning, suggesting its potential efficacy for PTSD treatment.

DBS also reversed neurocircuitry abnormalities by reducing activity in the basolateral amygdala, indicating a mechanism of action that may help restore normal fear processing in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal Cortex Deep Brain Stimulation Improves Fear and Anxiety-Like Behavior and Reduces Basolateral Amygdala Activity in a Preclinical Model of Posttraumatic Stress Disorder. Reznikov, R., Bambico, FR., Diwan, M., et al.[2022]

Research on Vietnam combat veterans with chronic PTSD suggests that prolonged exposure to high-intensity stimulation leads to significant changes in brain structure and function, particularly affecting neuronal and synaptic activity.

The study hypothesizes that these changes impair the brain's ability to regulate aggressive behavior and sleep patterns, contributing to the persistent symptoms of PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A neuropsychological hypothesis explaining posttraumatic stress disorders. Kolb, LC.[2022]

In patients with acute PTSD, traumatic memories trigger increased activity in brain regions associated with memory and emotion, such as the amygdala and hippocampus, indicating heightened emotional responses.

The study suggests that the neurofunctional changes in acute PTSD are more widespread and unstable compared to the more defined and stable abnormalities seen in chronic PTSD, highlighting the evolving nature of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurofunctional mechanisms of traumatic and non-traumatic memory in patients with acute PTSD following accident trauma. Piefke, M., Pestinger, M., Arin, T., et al.[2011]

In a study involving 12 male veterans with PTSD and 12 without, fMRI revealed that veterans with PTSD showed underactivation in the frontal cortex and overactivation in the temporal cortex during the encoding of neutral word pairs, indicating altered brain activity related to memory processing.

During the retrieval phase, veterans with PTSD exhibited underactivation in key brain areas, including the right frontal cortex and the left posterior hippocampus, suggesting that these neural changes contribute to their memory performance deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural correlates of associative learning and memory in veterans with posttraumatic stress disorder. Geuze, E., Vermetten, E., Ruf, M., et al.[2008]

In a study of 98 adults at risk for PTSD, acute resting-state functional connectivity (rsFC) of the hippocampus was found to significantly predict PTSD symptom severity six months after trauma, indicating its potential as a biomarker for PTSD risk.

The study utilized advanced machine learning techniques to analyze whole-brain rsFC patterns, demonstrating that these patterns can forecast future PTSD symptoms even after accounting for other factors like baseline PTSD symptoms and levels of depression and anxiety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach. Fitzgerald, JM., Webb, EK., Weis, CN., et al.[2023]

Citations

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

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder. [2023]

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. 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]

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

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

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

Neuroanatomical features in soldiers with post-traumatic stress disorder. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Prefrontal Cortex Deep Brain Stimulation Improves Fear and Anxiety-Like Behavior and Reduces Basolateral Amygdala Activity in a Preclinical Model of Posttraumatic Stress Disorder. [2022]

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

A neuropsychological hypothesis explaining posttraumatic stress disorders. [2022]

9. England pubmed.ncbi.nlm.nih.gov

The neurofunctional mechanisms of traumatic and non-traumatic memory in patients with acute PTSD following accident trauma. [2011]

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

Neural correlates of associative learning and memory in veterans with posttraumatic stress disorder. [2008]

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

Hippocampal Resting-State Functional Connectivity Forecasts Individual Posttraumatic Stress Disorder Symptoms: A Data-Driven Approach. [2023]