Clinical trial NCT04518007: Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder
Official title: Hyperbaric Oxygen Therapy for Chronic Unremitting Post-Traumatic Stress Disorder (PTSD): a Prospective, Randomized, Double Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Traumatic Stress Disorder
Keywords: hyperbaric oxygen therapy
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-08-19
Enrollment: 56
Sex: MALE
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: hyperbaric oxygen therapy (2ATA, 100% oxygen) vs. sham (1.1ATA, 21% oxygen)
Primary purpose: TREATMENT

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

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

Eligibility 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

Primary outcomes:
measure: PTSD symptoms
timeFrame: Change from Baseline immediately after the intervention
Secondary outcomes:
measure: depression
timeFrame: Change from Baseline immediately after the intervention
measure: Changes in growth following a traumatic event
timeFrame: Change from Baseline immediately after the intervention
measure: wellbeing
timeFrame: Change from Baseline immediately after the intervention
measure: emotional regulation
timeFrame: Change from Baseline immediately after the intervention
measure: global distress
timeFrame: Change from Baseline immediately after the intervention
measure: sleep quality
timeFrame: Change from Baseline immediately after the intervention
measure: Depression, anxiety and stress
timeFrame: Change from Baseline immediately after the intervention
measure: Daily documentation of symptoms
timeFrame: daily during intervention, up to 16 weeks
measure: Mind streams cognitive health assessment (Mind streams)
timeFrame: Change from Baseline immediately after the intervention
measure: MRI Imaging
timeFrame: Change from Baseline immediately after the intervention
measure: Brain SPECT
timeFrame: Change from Baseline immediately after the intervention
measure: Cardiopulmonary exercise test
timeFrame: Change from Baseline immediately after the intervention
measure: Immune system
timeFrame: Change from Baseline immediately after the intervention
Other outcomes:
Locations:
city: Zerifin
country: Israel
facility: Dialysis Clinic in Asaf Harofhe Medical Center
Study officials:
affiliation: Asaf-Harofhe MC
name: Keren Doenyas
role: PRINCIPAL_INVESTIGATOR
References: