PTSDNCT05883397
Enhanced Hippocampal Neuroplasticity for Surfacing of Inaccessible Traumatic Memories in Veterans With PTSD
A study testing HBOT and Hippocampal training in people with PTSD and Peritraumatic Amnesia, run by Assaf-Harofeh Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 60 years, men only
- Conditions the study is for
- PTSD, Peritraumatic Amnesia
- What is being tested?
- HBOT and Hippocampal training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- 25 May 2023to 1 Aug 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of PTSD
- A history of trauma of at least one course of trauma-focused psychotherapy
- The presence of peri-traumatic amnesia
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Assaf-Harofeh Medical Center
Ramla, 70300
Shai Efrati, MD, 97289779395, hbo@asaf.health.gov.il
keren doenyas-barak, MD, 97289779395, PTSD-hbo@shamir.gov.il
About this study
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.
Read more
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.
Read the 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
- Being tested
- HBOT, Hippocampal training
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBOTOther
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 trainingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| HBOT | Active comparator | 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. Receives: Other: HBOT |
| HBOT + hippocampal training | Active comparator | 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. Receives: Other: HBOT; Other: Hippocampal training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in memory gaps (as assessed by the traumatic scene form)
traumatic scene form will be used to assess memory gaps. The intensity of each part sensation will be scored between 0 and 10 (higher score reflects stronger memory). A time line of the event will be drown, and amnestic parts of the memory will be marked (the presumed amnestic time will be evaluated in minutes)
Measured: through study completion, an average of 4 months
Time to inaccessible memory surfacing
Daily questionnaire will be used to assess surfacing of new memories. The time of memory surfacing will be defined (session number)
Measured: through study completion, an average of 4 months
Secondary outcomes (5)
Change in brain activity as assessed by fMRI (functional magnetic resonance imaging)
Three different fMRI paradigms will be used to assess hippocampal function, prefrontal cortex activity and the response to the traumatic memory
Measured: through study completion, an average of 4 months
cognitive performance as assessed using "Neurotrax"
Global Score is calculated based on the scores given for Memory performance, Attention, Information Processing speed, Executive Function and Motor skills.
The score ranges between 0 and 100, and higher score reflects better performance.
Measured: through study completion, an average of 4 months
RAVLT memory test
The test is designed as a list-learning paradigm in which the patient hears a list of 15 nouns and is asked to recall as many words from the list as possible. After five repetitions of free-recall, a second "interference" list (List B) is presented in the same manner, and the participant is asked to recall as many words from List B as possible. After the interference trial, the participant is immediately asked to recall the words from List A, which she or he heard five times previously. After a 20 min delay, the participant is asked to again recall the words from List A. After this "delayed recall" task, a list of 50 words is presented containing all of the words from Lists A and B, in addition to 20 phonemically and/or semantically similar words. The multiple memory processes assessed as a global score, called "Total Learning" The score ranges between 0 and 100, and higher score reflects better performance.
Measured: through study completion, an average of 4 months
ROCFT memory test
Copy Z Immediate recall Raw Delayed recall Z will be used to evaluate memory performance, higher scores reflects better performance.
Measured: through study completion, an average of 4 months
Verbal Pairs memory test
Recall Total Score First Recall Total Score Learning Slope Delayed List Recall Score Percent retention Recognition Score will be used to evaluate memory performance, higher scores reflects better performance.
Measured: through study completion, an average of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2023
- Study start25 May 2023
- Primary completion1 May 2025 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assaf-Harofeh Medical Center
- Sponsor type
- Other government
- Collaborators
- Weizmann Institute of Science, Office of Naval Research (ONR)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05883397
- Sponsor's protocol ID
- 90-22
- Status last verified
- May 2023
- First submitted
- 5 Mar 2023
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared with other researches.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhanced Hippocampal Neuroplasticity for Surfacing of Inaccessible Traumatic Memories in Veterans With PTSD
- ClinicalTrials.gov ID
- NCT05883397
- Acronym / sponsor ID
- 90-22
- Conditions
- PTSD, Peritraumatic Amnesia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assaf-Harofeh Medical CenterOther government
- Collaborators
- Weizmann Institute of Science, Office of Naval Research (ONR)
- Study start
- 25 May 2023 (actual)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 1 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| HBOT | Active comparator | Other: HBOTParticipants 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. |
| HBOT + hippocampal training | Active comparator | Other: HBOT, Other: Hippocampal trainingParticipants 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. |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Diagnosis of PTSD
- A history of trauma of at least one course of trauma-focused psychotherapy
- The presence of peri-traumatic amnesia
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HBOTParticipants 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. | Other | HBOT, HBOT + hippocampal training |
| Hippocampal trainingHippocampal 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. | Other | HBOT + hippocampal training |
Primary outcome
Changes in memory gaps (as assessed by the traumatic scene form)
Time frame: through study completion, an average of 4 months
traumatic scene form will be used to assess memory gaps. The intensity of each part sensation will be scored between 0 and 10 (higher score reflects stronger memory). A time line of the event will be drown, and amnestic parts of the memory will be marked (the presumed amnestic time will be evaluated in minutes)
Time to inaccessible memory surfacing
Time frame: through study completion, an average of 4 months
Daily questionnaire will be used to assess surfacing of new memories. The time of memory surfacing will be defined (session number)
5 secondary outcomes
Change in brain activity as assessed by fMRI (functional magnetic resonance imaging)
Time frame: through study completion, an average of 4 months
cognitive performance as assessed using "Neurotrax"
Time frame: through study completion, an average of 4 months
RAVLT memory test
Time frame: through study completion, an average of 4 months
ROCFT memory test
Time frame: through study completion, an average of 4 months
Verbal Pairs memory test
Time frame: through study completion, an average of 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- Individual participant dataSharing planned: No. Individual participant data will not be shared with other researches.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HBOT and Hippocampal training in people with PTSD and Peritraumatic Amnesia, run by Assaf-Harofeh Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact keren Doenyas-Barak, MD (0544215487, kerendoenyas@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in memory gaps (as assessed by the traumatic scene form) (time frame: through study completion, an average of 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2023.