Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder

NCT ID: NCT04518007

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-25
• Study Completion Date: 2024-02-26

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

Conditions

Post Traumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

hyperbaric oxygen therapy

Intervention Type: 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.

hyperbaric oxygen therapy (HBOT) sham treatment

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.

Group Type: SHAM_COMPARATOR

hyperbaric oxygen therapy

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Assaf-Harofeh Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keren Doenyas

Role: PRINCIPAL_INVESTIGATOR

Asaf-Harofhe MC

Locations

Dialysis Clinic in Asaf Harofhe Medical Center

Ẕerifin, , Israel

Countries

Israel

References

Danan D, Grosskopf Y, Mayo A, Efrati S, Kutz I, Lang E, Alon U, Doenyas-Barak K. Hyperbaric Oxygen Therapy for PTSD: Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment. Brain Behav. 2025 Aug;15(8):e70757. doi: 10.1002/brb3.70757.

Reference Type: DERIVED

PMID: 40847457 (View on PubMed)

Doenyas-Barak K, Kutz I, Lang E, Assouline A, Hadanny A, Aberg KC, Levi G, Beberashvili I, Mayo A, Efrati S. Hyperbaric Oxygen Therapy for Veterans With Combat-Associated Posttraumatic Stress Disorder: A Randomized, Sham-Controlled Clinical Trial. J Clin Psychiatry. 2024 Nov 10;85(4):24m15464. doi: 10.4088/JCP.24m15464.

Reference Type: DERIVED

PMID: 39566051 (View on PubMed)

Other Identifiers

291-19

Identifier Type: -

Identifier Source: org_study_id