Enhanced Hippocampal Neuroplasticity for Surfacing of Inaccessible Traumatic Memories in Veterans With PTSD

NCT ID: NCT05883397

Last Updated: 2023-06-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-25
• Study Completion Date: 2025-08-01

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.

Conditions

PTSD; Peritraumatic Amnesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

HBOT

Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA (atmospheres), with five-minute air brakes every 20 minutes.

Group Type: ACTIVE_COMPARATOR

HBOT

Intervention Type: OTHER

Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA, with five-minute air breaks every 20 minutes.

HBOT + hippocampal training

Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA, with five-minute air breaks every 20 minutes.

Hippocampal training: This will combine physical and cognitive training. Training will be given 3 times per week, prior to the next HBOT, and more than 20 hours after the last HBOT session.

Group Type: ACTIVE_COMPARATOR

HBOT

Intervention Type: OTHER

Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA, with five-minute air breaks every 20 minutes.

Hippocampal training

Intervention Type: OTHER

Hippocampal training: This will combine physical and cognitive training. Training will be given 3 times per week, prior to the next HBOT, and more than 20 hours after the last HBOT session.

Interventions

HBOT

Participants will be treated in a multiplace chamber (HAUX-Life-Support GmbH) for a total of 60 daily sessions, five days a week. Each session will consist of 90 minutes exposure to 100% oxygen at 2 ATA, with five-minute air breaks every 20 minutes.

Intervention Type: OTHER

Hippocampal training

Hippocampal training: This will combine physical and cognitive training. Training will be given 3 times per week, prior to the next HBOT, and more than 20 hours after the last HBOT session.

Intervention Type: OTHER

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Weizmann Institute of Science

OTHER

Sponsor Role: collaborator

Office of Naval Research (ONR)

FED

Sponsor Role: collaborator

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Assaf-Harofeh Medical Center

Ramla, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

keren Doenyas-Barak, MD

Role: CONTACT

kerendoenyas@gmail.com

0544215487

Facility Contacts

Shai Efrati, MD

Role: primary

hbo@asaf.health.gov.il

97289779395

keren doenyas-barak, MD

Role: backup

PTSD-hbo@shamir.gov.il

97289779395

Other Identifiers

90-22

Identifier Type: -

Identifier Source: org_study_id