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Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder (HBOT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04518007
Recruitment Status : Recruiting
First Posted : August 19, 2020
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
Assaf-Harofeh Medical Center

Brief Summary:
The study evaluates the effect of hyperbaric oxygen therapy on veterans with combat-associated PTSD in an double blind sham control study.

Condition or disease Intervention/treatment Phase
Post Traumatic Stress Disorder Device: hyperbaric oxygen therapy Not Applicable

Detailed Description:

Post-traumatic stress disorder (PTSD) is the brain's long-term imprint of a traumatic event. PTSD is characterized by intrusive thoughts, nightmares and flashbacks of past traumatic events, avoidance of trauma reminders, hypervigilance, and sleep disturbance, all of which lead to considerable social, occupational, and interpersonal dysfunction. The current available treatments for PTSD include medications and psychotherapy. However, a substantial proportion of patients have treatment resistant PTSD.

In recent years there is growing evidence that traumatic events can induce changes in the brain's structure and function that may persist months or even years after the acute event. The "non-healing brain wound" can be visualized using functional imaging. The new insight regarding the biological nature of PTSD obligates biological intervention that can induce neuroplasticity and recovery of the damage brain tissue.

Hyperbaric Oxygen Therapy (HBOT) includes the inhalation of 100% oxygen in a pressurized chamber with pressures exceeding 1 atmosphere absolute (ATA), thus enhancing the amount of oxygen dissolved in the body's tissues. It is now understood that the combined action of both hyperoxia and hyperbaric pressure together with, oxygen fluctuations generated by a pre-defined protocol may target both oxygen and pressure sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Moreover, these genes induce the proliferation of stem cells, augmented circulating levels of endothelial progenitor cells (EPCs) and angiogenesis factors, which induce angiogenesis and improved blood flow in the ischemic area. In recent years there is growing evidence that HBOT induced brain neuroplasticity leads to repair of chronically impaired brain functions in post-stroke and in traumatic brain injury (TBI) patients with prolonged post-concussion syndrome, even years after the brain insult, as well as in healthy aging adults. HBOT can also induce neuroplasticity and significantly improve the clinical symptoms of the most common prototype of central sensitization syndrome - fibromyalgia syndrome.

The effects of HBOT on patients suffering from chronic unremitting PTSD due to combat trauma were evaluated in a pilot study done in the investigator's institute. The recently done study included veterans with combat associated PTSD according to the Ministry of Defense (MOD) criteria, who failed to improve using the current available treatments. The results of the study demonstrated the beneficial effect of HBOT in this unfortunate severely injured unremitting PTSD population. Clinically significant improvement was demonstrated in a major fraction of study participants. In correlation with the clinical improvement, a significant improvement in brain activity was demonstrated in the functional MRI imaging.

The aim of the current study is to evaluate the effect of HBOT on chronic unremitting combat associated PTSD in an double blind sham control study

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: hyperbaric oxygen therapy (2ATA, 100% oxygen) vs. sham (1.1ATA, 21% oxygen)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Hyperbaric Oxygen Therapy for Chronic Unremitting Post-Traumatic Stress Disorder (PTSD): a Prospective, Randomized, Double Blind Study
Actual Study Start Date : February 25, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Active Comparator: hyperbaric oxygen therapy (HBOT) active treatment
The HBOT protocol consists of 60 daily sessions, five times per week, each session lasting 90 minutes, of 100% oxygen at 2 ATA and 5-minute air breaks every 20 minutes.
Device: hyperbaric oxygen therapy

The HBOT protocol consists of 60 daily sessions, five times per week, each session lasting 90 minutes.

Investigational product:

Multiplace hyperbaric oxygen chamber (Haux, Germany) located at the Sago l Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Israel.


Sham Comparator: sham
All the conditions provided in the HBOT intervention will be provided in the sham intervention. However, in contrast to the HBOT, where the pressure will go up to 2 ATA, in the sham condition the pressure will go up to 1.1 ATA during the first five minutes of the session with noise of circulating air, and then decrease slowly during the next half hour to 1.0 ATA and the oxygen level will be 21% The initial 1.1 ATA level will provide a minimal pressure sensation in the ears, with the same nurse advice on pumping the ears. In the last five minutes of the session, the air will be circulated again with its related noises. Sham and HBOT sessions will never be adjacent, so subjects from the two groups cannot meet and discuss the session and its effects.
Device: hyperbaric oxygen therapy

The HBOT protocol consists of 60 daily sessions, five times per week, each session lasting 90 minutes.

Investigational product:

Multiplace hyperbaric oxygen chamber (Haux, Germany) located at the Sago l Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Israel.





Primary Outcome Measures :
  1. PTSD symptoms [ Time Frame: Change from Baseline immediately after the intervention ]
    PTSD symptoms will be assessed by the PTSD Clinician-Administered PTSD Scale (CAPS) questionnaire.


Secondary Outcome Measures :
  1. depression [ Time Frame: Change from Baseline immediately after the intervention ]
    Beck depression inventory II

  2. Changes in growth following a traumatic event [ Time Frame: Change from Baseline immediately after the intervention ]
    The post-traumatic growth inventory (PTGI)

  3. wellbeing [ Time Frame: Change from Baseline immediately after the intervention ]
    Changes will be measured by the wellbeing inventory (WBI).

  4. emotional regulation [ Time Frame: Change from Baseline immediately after the intervention ]
    Changes in emotional regulation will be measured by the emotion regulation questionnaire (ERQ).

  5. global distress [ Time Frame: Change from Baseline immediately after the intervention ]
    The brief symptom inventory (BSI)

  6. sleep quality [ Time Frame: Change from Baseline immediately after the intervention ]
    Changes in sleep patterns will be measured using the Pittsburgh sleep quality index (PSQI).

  7. Depression, anxiety and stress [ Time Frame: Change from Baseline immediately after the intervention ]
    Depression, anxiety and stress will be evaluated using scale-21 items (DASS-21)

  8. Daily documentation of symptoms [ Time Frame: daily during intervention, up to 16 weeks ]
    Daily distress and change in symptoms will be evaluated using visual assessment scale (VAS) based questionnaire

  9. Mind streams cognitive health assessment (Mind streams) [ Time Frame: Change from Baseline immediately after the intervention ]
    memory, attention and information process will be evaluated using the Mind streams cognitive health assessment (Mind streams)

  10. MRI Imaging [ Time Frame: Change from Baseline immediately after the intervention ]
    At each of the evaluations, patients will undergo structural and functional MRI scanning. Images will be acquired on Vida 3 Tesla Scanner, configured with a 64-channel receiver head coils (Siemens Healthcare, Erlangen, Germany) at Shamir medical center radiology department.

  11. Brain SPECT [ Time Frame: Change from Baseline immediately after the intervention ]
    SPECT will be conducted with 925-1,110 (25-30 mCi) of technetium-99m-methyl-cysteinate-dimmer (Tc-99m-ECD) at 40-60 min post injection, using a dual detector gamma camera (Siemens Medical Systems) equipped with high resolution collimators

  12. Cardiopulmonary exercise test [ Time Frame: Change from Baseline immediately after the intervention ]
    The cardiopulmonary exercise test (CPET) is a noninvasive measurement of the cardiovascular system, respiratory system and muscles

  13. Immune system [ Time Frame: Change from Baseline immediately after the intervention ]
    Inflammatory cytokines: blood tests will include: interleukin (IL) IL-1, IL-6, tumor necrosis factor-alpha, C reactive protein and T cells panel



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject willing and able to read, understand and sign an informed consent
  • Age 25-60
  • Five years or more after the last traumatic exposure
  • CAPS-5 score PTSD symptoms questionnaire ≥ 20.
  • Failure to improve after at least one line of conventional therapy, such as prolonged exposure, trauma related psychotherapy, eye movement desensitization therapy (EMDR).
  • Stable psychological and pharmacological treatment for more than three months prior to inclusion.

Exclusion Criteria:

  • Inability to attend scheduled clinic visits and/or comply with the study protocol.
  • History of TBI or any other brain pathology
  • Active malignancy
  • Substance use at baseline, except for prescribed cannabis if vaporized or taken PO as tincture
  • Current manic episode or psychotic disorders
  • Serious suicidal ideation
  • Severe or unstable physical disorders or major cognitive deficits at baseline
  • for any reason prior to study enrollment
  • Chest pathology incompatible with pressure changes (including active asthma)
  • Ear or Sinus pathology incompatible with pressure changes
  • An inability to perform an awake brain MRI
  • active smoking

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04518007


Contacts
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Contact: Keren Doenyas-Barak, MD 972544215487 kerendoenyas@gmail.com
Contact: Shai a Efrati, MD 972549212866 efratishai@outlook.com

Locations
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Israel
Dialysis Clinic in Asaf Harofhe Medical Center Recruiting
Zerifin, Israel, 70300
Contact: Keren Doenyas, MD    972544215487    kerendoenyas@gmail.com   
Sponsors and Collaborators
Assaf-Harofeh Medical Center
Investigators
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Principal Investigator: Keren Doenyas Asaf-Harofhe MC
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Responsible Party: Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier: NCT04518007    
Other Study ID Numbers: 291-19
First Posted: August 19, 2020    Key Record Dates
Last Update Posted: June 28, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Assaf-Harofeh Medical Center:
hyperbaric oxygen therapy
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders