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

Primary Purpose

PTSD, Peritraumatic Amnesia

Status
Recruiting
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
HBOT
Hippocampal training
Sponsored by
Assaf-Harofeh Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PTSD

Eligibility Criteria

25 Years - 60 Years (Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Assaf-Harofeh Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

HBOT

HBOT + hippocampal training

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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)
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)

Secondary Outcome Measures

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
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.
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.
ROCFT memory test
Copy Z Immediate recall Raw Delayed recall Z will be used to evaluate memory performance, higher scores reflects better performance.
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.

Full Information

First Posted
March 5, 2023
Last Updated
May 29, 2023
Sponsor
Assaf-Harofeh Medical Center
Collaborators
Weizmann Institute of Science, Office of Naval Research (ONR)
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1. Study Identification

Unique Protocol Identification Number
NCT05883397
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2023 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
August 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assaf-Harofeh Medical Center
Collaborators
Weizmann Institute of Science, Office of Naval Research (ONR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PTSD, Peritraumatic Amnesia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Care ProviderInvestigatorOutcomes Assessor
Masking Description
Care providers, Investigator and assessors will be blinded to the participants' allocation.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HBOT
Arm Type
Active Comparator
Arm Description
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.
Arm Title
HBOT + hippocampal training
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
HBOT
Intervention Description
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
Intervention Name(s)
Hippocampal training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in memory gaps (as assessed by the traumatic scene form)
Description
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 Frame
through study completion, an average of 4 months
Title
Time to inaccessible memory surfacing
Description
Daily questionnaire will be used to assess surfacing of new memories. The time of memory surfacing will be defined (session number)
Time Frame
through study completion, an average of 4 months
Secondary Outcome Measure Information:
Title
Change in brain activity as assessed by fMRI (functional magnetic resonance imaging)
Description
Three different fMRI paradigms will be used to assess hippocampal function, prefrontal cortex activity and the response to the traumatic memory
Time Frame
through study completion, an average of 4 months
Title
cognitive performance as assessed using "Neurotrax"
Description
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.
Time Frame
through study completion, an average of 4 months
Title
RAVLT memory test
Description
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.
Time Frame
through study completion, an average of 4 months
Title
ROCFT memory test
Description
Copy Z Immediate recall Raw Delayed recall Z will be used to evaluate memory performance, higher scores reflects better performance.
Time Frame
through study completion, an average of 4 months
Title
Verbal Pairs memory test
Description
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.
Time Frame
through study completion, an average of 4 months

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Only male will be recruited to the study
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
keren Doenyas-Barak, MD
Phone
0544215487
Email
kerendoenyas@gmail.com
Facility Information:
Facility Name
Assaf-Harofeh Medical Center
City
Ramla
ZIP/Postal Code
70300
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shai Efrati, MD
Phone
97289779395
Email
hbo@asaf.health.gov.il
First Name & Middle Initial & Last Name & Degree
keren doenyas-barak, MD
Phone
97289779395
Email
PTSD-hbo@shamir.gov.il
First Name & Middle Initial & Last Name & Degree
keren doenyas, MD
First Name & Middle Initial & Last Name & Degree
Shai Efrati, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will not be shared with other researches.

Learn more about this trial

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

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