Clinical trial NCT05883397: Enhanced Hippocampal Neuroplasticity for Surfacing of Inaccessible Traumatic Memories in Veterans With PTSD
Official title: Enhanced Hippocampal Neuroplasticity for Surfacing of Inaccessible Traumatic Memories in Veterans With PTSD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PTSD
Peritraumatic Amnesia
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Weizmann Institute of Science
name: Office of Naval Research (ONR)
First posted: 2023-06-01
Enrollment: 60
Sex: MALE
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be recruited from veterans' clinics and veterans' organizations. After screening, eligible participants will undergo baseline evaluation. Enrolled participants will be 1:1 randomly assigned to the HBOT or HBOT + hippocampal training, according to a computer-generated randomization list. Assessors will be blinded to the participants' allocation.

During the study period, all the participants will continue their psychological and pharmacological treatment as prior to their inclusion in the study. Any changes in the frequency of psychologic treatment or pharmacotherapy dose will be reported and documented.

The study is designed as a per protocol trial, and thus, participants will only be included in the analysis if they completed the treatment protocol and attained study analysis.
Primary purpose: TREATMENT

Brief summary: Hyperbaric oxygen therapy (HBOT) includes the inhalation of 100% oxygen at pressures exceeding one atmosphere absolute. HBOT has been applied worldwide, mostly for chronic non-healing wounds. Our team demonstrated that HBOT induced hippocampal neuroplasticity in veterans with long-standing treatment-resistant PTSD; this led to enhanced memory recovery and significant improvement in PTSD symptoms.

Both physical activity, such as aerobic exercise, and cognitive training were shown to support neurogenesis in the hippocampus. Therefore, the current study aims to evaluate whether hippocampal training, induced by physical and cognitive training, will augment the hippocampal neuroplasticity effect of HBOT and further enhance recovery of inaccessible memories in veterans with PTSD.

The protocol will include forty male veterans aged 25 to 60 years, with combat-associated PTSD and peritraumatic amnesia, who will receive either HBOT alone or HBOT and hippocampal training. The HBOT protocol will consist of 60 daily sessions, 90-minutes each, five days a week. Hippocampal training will combine physical and cognitive training 3 times per week, prior to HBOT sessions. Detailed psychological evaluation, anatomic and functional MRI, electroencephalogram and autonomic nervous system data will be obtained at baseline, and during and after treatment.

The proposed study offers a new approach of biological treatment for memory manipulations. The findings will help elucidate the mechanism of PTSD-related memory impairment and is expected to contribute to the development of biological memory manipulations for treating PTSD and other memory-related conditions.

Detailed description: Our memory constructs a sense of coherence and defines the way we perceive the world. Effective encoding of memories in an adequate context, and their deliberate retrieval at a later time, are crucial for maintaining biographic continuity, and are both heavily dependent on hippocampal function.

Post-traumatic stress disorder (PTSD) can be considered a prototype disorder in which a stressogenic event leads to hippocampal malfunction and mal-encoding of a traumatic memory. Persistent hippocampal dysfunction contributes to the unremitting nature of PTSD years after the acute event. The upshot is not only amnesia, but also difficulty in memory integration in the context of time and location, and the feeling that the traumatic event is present all the time and everywhere. Improved hippocampal function may contribute to better access to memories of a traumatic event and to memory contextualization and neutralization. Memory processing is essential for PTSD recovery.

Hyperbaric oxygen therapy (HBOT) includes the inhalation of 100% oxygen at pressures exceeding one atmosphere absolute. HBOT has been applied worldwide, mostly for chronic non-healing wounds. Our team demonstrated that HBOT induced hippocampal neuroplasticity in veterans with long-standing treatment-resistant PTSD; this led to enhanced memory recovery and significant improvement in PTSD symptoms. The investigators also demonstrated effects of HBOT on memory recovery among women with fibromyalgia due to childhood sexual abuse.

Both physical activity, such as aerobic exercise, and cognitive training were shown to support neurogenesis in the hippocampus. Therefore, the current study aims to evaluate whether hippocampal training, induced by physical and cognitive training, will augment the hippocampal neuroplasticity effect of HBOT and further enhance recovery of inaccessible memories in veterans with PTSD.

The protocol will include forty male veterans aged 25 to 60 years, with combat-associated PTSD and peritraumatic amnesia, who will receive either HBOT alone or HBOT and hippocampal training. The HBOT protocol will consist of 60 daily sessions, 90-minutes each, five days a week. Hippocampal training will combine physical and cognitive training 3 times per week, prior to HBOT sessions. Detailed psychological evaluation, anatomic and functional MRI, electroencephalogram and autonomic nervous system data will be obtained at baseline, and during and after treatment.

The proposed study offers a new approach of biological treatment for memory manipulations. The findings will help elucidate the mechanism of PTSD-related memory impairment, and is expected to contribute to the development of biological memory manipulations for treating PTSD and other memory-related conditions.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of PTSD
* A history of trauma of at least one course of trauma-focused psychotherapy
* The presence of peri-traumatic amnesia

Exclusion Criteria:

* A history of traumatic brain injury or any other known brain pathology except PTSD
* Active smoking
* Drugs or alcohol abuse other than prescribed cannabis
* Active asthma, lung pathology, epilepsy or otolaryngological disease incompatible with HBOT
* The presence of shards or another contraindication for MRI

Primary outcomes:
measure: Changes in memory gaps (as assessed by the traumatic scene form)
timeFrame: through study completion, an average of 4 months
measure: Time to inaccessible memory surfacing
timeFrame: through study completion, an average of 4 months
Secondary outcomes:
measure: Change in brain activity as assessed by fMRI (functional magnetic resonance imaging)
timeFrame: through study completion, an average of 4 months
measure: cognitive performance as assessed using "Neurotrax"
timeFrame: through study completion, an average of 4 months
measure: RAVLT memory test
timeFrame: through study completion, an average of 4 months
measure: ROCFT memory test
timeFrame: through study completion, an average of 4 months
measure: Verbal Pairs memory test
timeFrame: through study completion, an average of 4 months
Other outcomes:
Locations:
city: Ramla
country: Israel
facility: Assaf-Harofeh Medical Center
Study officials:
References: