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Completed

NCT Number: NCT04518007

Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder

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

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Key information

Age range

25 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Dialysis Clinic in Asaf Harofhe Medical Center

Ẕerifin, 70300, Israel

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

hyperbaric oxygen therapy

Device

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 outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Assaf-Harofeh Medical Center

Other Gov

Registry information

Official study title

Hyperbaric Oxygen Therapy for Chronic Unremitting Post-Traumatic Stress Disorder (PTSD): a Prospective, Randomized, Double Blind Study

Acronym: HBOT

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Aug 19, 2020
Registry last updated
Jul 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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