Post Traumatic Stress DisorderHBOTNCT04518007
Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder
A study testing hyperbaric oxygen therapy in people with Post Traumatic Stress Disorder, run by Assaf-Harofeh Medical Center at 1 site in Israel.
Trial summary
The study evaluates the effect of hyperbaric oxygen therapy on veterans with combat-associated PTSD in an double blind sham control study. Read more about this study
- Who is it for?
- Ages 25 to 60 years, men only
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- hyperbaric oxygen therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteIsrael
- Study dates
- 25 Feb 2020to 26 Feb 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hyperbaric Oxygen Therapy for Chronic Unremitting Post-Traumatic Stress Disorder (PTSD): a Prospective, Randomized, Double Blind Study
The study evaluates the effect of hyperbaric oxygen therapy on veterans with combat-associated PTSD in an double blind sham control study.
Read the 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
- Being tested
- hyperbaric oxygen therapy
- Keywords
- hyperbaric oxygen therapy
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hyperbaric oxygen therapyDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| hyperbaric oxygen therapy (HBOT) active treatment | Active comparator | 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. Receives: Device: hyperbaric oxygen therapy |
| hyperbaric oxygen therapy (HBOT) sham treatment | Sham comparator | 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. Receives: Device: hyperbaric oxygen therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
PTSD symptoms
PTSD symptoms will be assessed by the PTSD Clinician-Administered PTSD Scale (CAPS) questionnaire.
Measured: Change from Baseline immediately after the intervention
Secondary outcomes (13)
depression
Beck depression inventory II
Measured: Change from Baseline immediately after the intervention
Changes in growth following a traumatic event
The post-traumatic growth inventory (PTGI)
Measured: Change from Baseline immediately after the intervention
wellbeing
Changes will be measured by the wellbeing inventory (WBI).
Measured: Change from Baseline immediately after the intervention
emotional regulation
Changes in emotional regulation will be measured by the emotion regulation questionnaire (ERQ).
Measured: Change from Baseline immediately after the intervention
global distress
The brief symptom inventory (BSI)
Measured: Change from Baseline immediately after the intervention
sleep quality
Changes in sleep patterns will be measured using the Pittsburgh sleep quality index (PSQI).
Measured: Change from Baseline immediately after the intervention
Depression, anxiety and stress
Depression, anxiety and stress will be evaluated using scale-21 items (DASS-21)
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: Change from Baseline immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2020
- Study start25 Feb 2020
- Primary completion26 Jan 2024
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- hyperbaric oxygen therapy (2ATA, 100% oxygen) vs. sham (1.1ATA, 21% oxygen)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assaf-Harofeh Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Keren Doenyas, Principal investigator, Asaf-Harofhe MC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04518007
- Sponsor's protocol ID
- 291-19
- Acronym
- HBOT
- Status last verified
- Jul 2024
- First submitted
- 12 Mar 2020
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40847457Doenyas-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.
PubMed 39566051
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperbaric Oxygen Therapy for Chronic Unremitting Post-Traumatic Stress Disorder (PTSD): a Prospective, Randomized, Double Blind Study
- ClinicalTrials.gov ID
- NCT04518007
- Acronym / sponsor ID
- HBOT / 291-19
- Conditions
- Post Traumatic Stress Disorder
- Keywords
- hyperbaric oxygen therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Assaf-Harofeh Medical CenterOther government
- Study start
- 25 Feb 2020 (actual)
- Primary completion
- 26 Jan 2024 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 19 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- hyperbaric oxygen therapy (2ATA, 100% oxygen) vs. sham (1.1ATA, 21% oxygen)
| Arm | Type | Receives |
|---|---|---|
| hyperbaric oxygen therapy (HBOT) active treatment | Active comparator | Device: hyperbaric oxygen therapyThe 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. |
| hyperbaric oxygen therapy (HBOT) sham treatment | Sham comparator | Device: hyperbaric oxygen therapyAll 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. |
Who may qualify
- Ages
- 25 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hyperbaric oxygen therapyThe 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. | Device | hyperbaric oxygen therapy (HBOT) active treatment, hyperbaric oxygen therapy (HBOT) sham treatment |
Primary outcome
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.
13 secondary outcomes
depression
Time frame: Change from Baseline immediately after the intervention
Changes in growth following a traumatic event
Time frame: Change from Baseline immediately after the intervention
wellbeing
Time frame: Change from Baseline immediately after the intervention
emotional regulation
Time frame: Change from Baseline immediately after the intervention
global distress
Time frame: Change from Baseline immediately after the intervention
sleep quality
Time frame: Change from Baseline immediately after the intervention
Depression, anxiety and stress
Time frame: Change from Baseline immediately after the intervention
Daily documentation of symptoms
Time frame: daily during intervention, up to 16 weeks
Mind streams cognitive health assessment (Mind streams)
Time frame: Change from Baseline immediately after the intervention
MRI Imaging
Time frame: Change from Baseline immediately after the intervention
Brain SPECT
Time frame: Change from Baseline immediately after the intervention
Cardiopulmonary exercise test
Time frame: Change from Baseline immediately after the intervention
Immune system
Time frame: Change from Baseline immediately after the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Derived from this study: PubMed 40847457Danan 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.
- Derived from this study: PubMed 39566051Doenyas-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keren Doenyas principal investigator
Asaf-Harofhe MC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hyperbaric oxygen therapy in people with Post Traumatic Stress Disorder, run by Assaf-Harofeh Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PTSD symptoms (time frame: Change from Baseline immediately after the intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04518007, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.