Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder

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

Detailed Description
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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

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

Conditions
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Post Traumatic Stress Disorder

Intervention / Treatment
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* Device: hyperbaric oxygen therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: hyperbaric oxygen therapy (2ATA, 100% oxygen) vs. sham (1.1ATA, 21% oxygen)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: hyperbaric oxygen therapy (HBOT) active treatment<br>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<br>* 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.<br>|
| Sham Comparator: sham<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD symptoms | PTSD symptoms will be assessed by the PTSD Clinician-Administered PTSD Scale (CAPS) questionnaire. | Change from Baseline immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| depression | Beck depression inventory II | Change from Baseline immediately after the intervention | 
| Changes in growth following a traumatic event | The post-traumatic growth inventory (PTGI) | Change from Baseline immediately after the intervention | 
| wellbeing | Changes will be measured by the wellbeing inventory (WBI). | Change from Baseline immediately after the intervention | 
| emotional regulation | Changes in emotional regulation will be measured by the emotion regulation questionnaire (ERQ). | Change from Baseline immediately after the intervention | 
| global distress | The brief symptom inventory (BSI) | Change from Baseline immediately after the intervention | 
| sleep quality | Changes in sleep patterns will be measured using the Pittsburgh sleep quality index (PSQI). | Change from Baseline immediately after the intervention | 
| Depression, anxiety and stress | Depression, anxiety and stress will be evaluated using scale-21 items (DASS-21) | Change from Baseline immediately after the intervention | 
| Daily documentation of symptoms | Daily distress and change in symptoms will be evaluated using visual assessment scale (VAS) based questionnaire | daily during intervention, up to 16 weeks | 
| Mind streams cognitive health assessment (Mind streams) | memory, attention and information process will be evaluated using the Mind streams cognitive health assessment (Mind streams) | Change from Baseline immediately after the intervention | 
| MRI Imaging | 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. | Change from Baseline immediately after the intervention | 
| Brain SPECT | 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 | Change from Baseline immediately after the intervention | 
| Cardiopulmonary exercise test | The cardiopulmonary exercise test (CPET) is a noninvasive measurement of the cardiovascular system, respiratory system and muscles | Change from Baseline immediately after the intervention | 
| Immune system | Inflammatory cytokines: blood tests will include: interleukin (IL) IL-1, IL-6, tumor necrosis factor-alpha, C reactive protein and T cells panel | Change from Baseline immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperbaric oxygen therapy