Hyperbaric Oxygen Therapy for Post Traumatic Stress Disorder - a Pragmatic, Double Blinded Randomized Trial

NCT07473362 | Recruiting

• 1 other identifier: 2436-2024
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Post-traumatic stress disorder (PTSD), affecting approximately 6% of the general population and up to one-third of individuals exposed to combat zones and disasters, is a significant contributor to morbidity and mortality among IDF personnel. Hyperbaric oxygen therapy (HBOT), in which patients breathe oxygen at a partial pressure higher than 1 atmosphere in a hyperbaric chamber, has been investigated in the context of treating a wide range of neuropsychiatric disorders, including PTSD and mild traumatic brain injury (mTBI). Four controlled studies conducted in patients with mTBI, about half of whom also suffered from PTSD, have yielded conflicting conclusions regarding the potential efficacy of hyperbaric therapy. A single study involving approximately 30 patients with PTSD without mTBI demonstrated significant clinical improvement; however, it was characterized by several methodological limitations-chief among them the absence of blinding or a placebo control. None of the studies conducted to date have reported long-term findings (beyond one year), included patients with a short duration of symptoms ("early PTSD"), or included female participants. The aim of the proposed study is to conduct a prospective, double-blind, controlled investigation of the biological effect of hyperbaric therapy in PTSD, continuously throughout the hyperbaric treatment course, at the end of treatment, and during a substantial follow-up period of two years after treatment completion. We intend to include adult participants who are capable of providing informed consent and who meet DSM-5 diagnostic criteria for PTSD. In order to maintain a pragmatic study with high external validity, exclusion criteria will be limited to those indicating risk (concrete suicidality, or a history of manic or psychotic disorder) or factors likely to impair treatment efficacy (incompatibility with hyperbaric chamber treatment, inability to complete the full treatment protocol, or pregnancy). Participants who miss a substantial number of treatments (five consecutively or one-third of the total treatments) will be withdrawn from the study. The primary outcome measure will be the CAPS-5 questionnaire. In addition, PTSD symptom questionnaires, surveys assessing cognitive, executive, affective functioning, and health-related quality of life will be administered. An exploratory outcome will focus on sleep quantity and quality and physiological monitoring using wearable devices, currently considered the most promising biomarker in the context of PTSD. Following enrollment and the provision of informed consent, balanced randomization will be performed with respect to covariates previously described as potential confounders (such as age, duration, and severity of symptoms, …). Participants will receive 60 hyperbaric treatments, five days per week, at either 2.0 atmospheres or 2.5 atmospheres. Both the participants and the evaluating clinical staff will be blinded to treatment allocation.

Conditions

PTSD - Post Traumatic Stress Disorder

Keywords

PTSD; HBO; Hyperbaric Oxygen Therapy

Outcome Measures

Primary Outcomes (1)

• Primary Outcome

  The change in the Clinician-Administered PTSD Scale (CAPS)-5 score at the end of the treatment series compared to the baseline score

  12 weeks

Secondary Outcomes (7)

• Secondary Outcome

  12 weeks

• Secondary Outcome

  12 weeks

• Secondary Outcome

  12 weeks

• Secondary Outcome

  12 weeks

• Secondary Outcome

  12 weeks

Other Outcomes (3)

• Exploratory Outcomes

  12 weeks

• Exploratory Outcomes

  12 weeks

• Exploratory Outcomes

  12 weeks

Study Arms (2)

2.0 ata

EXPERIMENTAL

The treatment will be carried out in a HAUX STARMED multi-place pressure chamber (by HAUX LIFESUPPORT SYSTEMS, Cuxhaven, Germany) containing three sections (12+2+6 places, respectively). Ambulatory blood pressure measurement will be performed by an ambulatory blood pressure monitor (ABPM) model F11 (by SUNTECH). Measurement of sleep continuity and physiological monitoring will be performed using a combined pulse-oxymetry and accelerometry wearable device such as the Oura ring (Oulu. Finland).

Procedure: Hyperbaric Oxygen Therapy

2.5 ata

ACTIVE COMPARATOR

The treatment will be carried out in a HAUX STARMED multi-place pressure chamber (by HAUX LIFESUPPORT SYSTEMS, Cuxhaven, Germany) containing three sections (12+2+6 places, respectively). Ambulatory blood pressure measurement will be performed by an ambulatory blood pressure monitor (ABPM) model F11 (by SUNTECH). Measurement of sleep continuity and physiological monitoring will be performed using a combined pulse-oxymetry and accelerometry wearable device such as the Oura ring (Oulu. Finland).

Procedure: Hyperbaric Oxygen Therapy

Interventions

Hyperbaric Oxygen Therapy PROCEDURE

The treatment will be carried out in a HAUX STARMED multi-place pressure chamber (by HAUX LIFESUPPORT SYSTEMS, Cuxhaven, Germany) containing three sections (12+2+6 places, respectively). Ambulatory blood pressure measurement will be performed by an ambulatory blood pressure monitor (ABPM) model F11 (by SUNTECH). Measurement of sleep continuity and physiological monitoring will be performed using a combined pulse-oxymetry and accelerometry wearable device such as the Oura ring (Oulu. Finland).

2.0 ata; 2.5 ata

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18 years and up to 80 years
• Ability to understand the researcher's explanation and give informed consent.
• Any sex or gender (unlike previous studies, a significant effort will be made to include women in this study)
• A diagnosis of PTSD according to DSM-5 criteria with a severity that warrants discharge from military service.

You may not qualify if:

• The lack of ability to attend 120 daily (5 times/week) treatments at the INMI
• Current or past psychotic disorder
• Evidence of active suicidal ideation
• Evidence of past or present manic disorder
• Difficulty equalizing pressures, including pulmonary emphysema, significant sinusoidal obstruction, eustachian tube dysfunction, or an pneumothorax that is not drained.
• Known or suspected pregnancy.

Sponsors & Collaborators

• Medical Corps, Israel Defense Force: lead

Study Sites (1)

Yarpa 112

Ramat Gan, Tel Aviv, Israel

RECRUITING

Related Publications (4)

• 18. Doenyas-Barak K, Kutz I, Levi G, Lang E, Beberashvili I, Efrati S. Hyperbaric Oxygen Therapy for Veterans With Treatment-resistant PTSD: A Longitudinal Follow-up Study. Mil Med. 2023 Jul 22;188(7-8):e2227-33. 19. Doenyas-Barak K, Kutz I, Lang E, Levi G, Efrati S. Memory surfacing among veterans with PTSD receiving hyperbaric oxygen therapy. Undersea Hyperb Med. 2023;50(4):395-401. 20. Hoge CW, Jonas WB. The ritual of hyperbaric oxygen and lessons for the treatment of persistent postconcussion symptoms in military personnel. JAMA Intern Med. 2015 Jan;175(1):53-4. 21. Hart BB, Weaver LK, Gupta A, Wilson SH, Vijayarangan A, Deru K, et al. Hyperbaric oxygen for mTBI-associated PCS and PTSD: Pooled analysis of results from Department of Defense and other published studies. Undersea Hyperb Med. 2019;46(3):353-83. 22. Schimmel S, El Sayed B, Lockard G, Gordon J, Young I, D'Egidio F, et al. Identifying the target traumatic brain injury population for hyperbaric oxygen therapy. Int J Mol Sci. 2023 Sep 27;24(19). 23. Doenyas-Barak K, Kutz I, Lang E, Merzbach R, Lev Wiesel R, Boussi-Gross R, et al. The use of hyperbaric oxygen for veterans with PTSD: basic physiology and current available clinical data. Front Neurosci. 2023 Oct 25;17:1259473. 24. Bugni FA, Canay IA, Shaikh AM. Inference under Covariate-Adaptive Randomization. J Am Stat Assoc. 2018 Jun 28;113(524):1784-96. 25. Kang M, Ragan BG, Park J-H. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008 Jun;43(2):215-21. 26. Ma W, Ye X, Tu F, Hu F. carat : An R Package for Covariate-Adaptive Randomization in Clinical Trials. J Stat Softw. 2023;107(2). 27. Hart BB, Wilson SH, Churchill S, Deru K, Weaver LK, Minnakanti M, et al. Extended follow-up in a randomized trial of hyperbaric oxygen for persistent post-concussive symptoms. Undersea Hyperb Med. 2019;46(3):313-27.

  BACKGROUND

• 12. Jones MW, Brett K, Han N, Wyatt HA. Hyperbaric Physics. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 13. Wolf EG, Prye J, Michaelson R, Brower G, Profenna L, Boneta O. Hyperbaric side effects in a traumatic brain injury randomized clinical trial. Undersea Hyperb Med. 2012 Dec;39(6):1075-82. 14. Weaver LK, Wilson SH, Lindblad AS, Churchill S, Deru K, Price RC, et al. Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial. Undersea Hyperb Med. 2018;45(2):129-56. 15. Miller RS, Weaver LK, Bahraini N, Churchill S, Price RC, Skiba V, et al. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. 2015 Jan;175(1):43-52. 16. Cifu DX, Hart BB, West SL, Walker W, Carne W. The effect of hyperbaric oxygen on persistent postconcussion symptoms. J Head Trauma Rehabil. 2014 Feb;29(1):11-20. 17. Doenyas-Barak K, Catalogna M, Kutz I, Levi G, Hadanny A, Tal S, et al. Hyperbaric oxygen therapy improves symptoms, brain's microstructure and functionality in veterans with treatment resistant post-traumatic stress disorder: A prospective, randomized, controlled trial. PLoS ONE. 2022 Feb 22;17(2):e0264161.

  BACKGROUND

• 6. Davis LL, Schein J, Cloutier M, Gagnon-Sanschagrin P, Maitland J, Urganus A, et al. The economic burden of posttraumatic stress disorder in the united states from a societal perspective. J Clin Psychiatry. 2022 Apr 25;83(3). 7. Mayer Y, Shiffman N, Bergmann E, Natoor M, Khazen S, Lurie I, et al. Mental Health Outcomes of Arab and Jewish Populations in Israel a Month after the Mass Trauma Events of October 7, 2023: A Cross-Sectional Survey of a Representative Sample. Psychiatry Res. 2024 Jun 15;339:116042. 8. Lin C-C, Huang K-L, Tung C-S, Liu Y-P. Hyperbaric oxygen therapy restored traumatic stress-induced dysregulation of fear memory and related neurochemical abnormalities. Behav Brain Res. 2019 Feb 1;359:861-70. 9. Peng Y, Feng S-F, Wang Q, Wang H-N, Hou W-G, Xiong L, et al. Hyperbaric oxygen preconditioning ameliorates anxiety-like behavior and cognitive impairments via upregulation of thioredoxin reductases in stressed rats. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 16;34(6):1018-25. 10. Hadanny A, Bechor Y, Catalogna M, Daphna-Tekoah S, Sigal T, Cohenpour M, et al. Hyperbaric Oxygen Therapy Can Induce Neuroplasticity and Significant Clinical Improvement in Patients Suffering From Fibromyalgia With a History of Childhood Sexual Abuse-Randomized Controlled Trial. Front Psychol. 2018 Dec 17;9:2495. 11. Harch PG, Andrews SR, Rowe CJ, Lischka JR, Townsend MH, Yu Q, et al. Hyperbaric oxygen therapy for mild traumatic brain injury persistent postconcussion syndrome: a randomized controlled trial. Med Gas Res. 2020;10(1):8-20.

  BACKGROUND

• 1. Parr NJ, Anderson J, Veazie S. Evidence Brief: Hyperbaric Oxygen Therapy for Traumatic Brain Injury and/or Post-traumatic Stress Disorder. Washington (DC): Department of Veterans Affairs (US); 2021. 2. Andrews SR, Harch PG. Systematic review and dosage analysis: hyperbaric oxygen therapy efficacy in the treatment of posttraumatic stress disorder. Front Neurol. 2024 May 31;15:1360311. 3. Mozayeni BR, Duncan W, Zant E, Love TL, Beckman RL, Stoller KP. The National Brain Injury Rescue and Rehabilitation Study - a multicenter observational study of hyperbaric oxygen for mild traumatic brain injury with post-concussive symptoms. Med Gas Res. 2019;9(1):1-12. 4. Harch PG. Systematic review and dosage analysis: hyperbaric oxygen therapy efficacy in mild traumatic brain injury persistent postconcussion syndrome. Front Neurol. 2022 Mar 17;13:815056. 5. Bennett MH. Evidence brief: hyperbaric oxygen therapy (HBOT) for traumatic brain injury and/or post-traumatic stress disorder. Diving Hyperb Med. 2018 Jun 30;48(2):115.

  BACKGROUND

MeSH Terms

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Central Study Contacts

Evan Gur, M.D

CONTACT

0542555655; ostyly@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All data collection will be carried out solely by the investigators outlined below. A designated clinical research form (CRF) using microsoft excel will be created to handle all data collected. All identified data will be saved on a designated unclassified (בלמ"ס) password protected computed. Access will be restricted to the abovementioned investigators. The CRF will be encrypted by a 128 bit RAS protocol. Removing all identifiers (including dates - to be replaced by time intervals, names, addresses, ID, military ID and phone numbers) and coding the information will be performed by Mj. Dror Ofir, PhD, who'll be keeping the coding key. Handling coded information will be performed on a separate, unclassified, password protected and designated computer, access to which will be restricted to investigators handling data analysis as detailed below.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a double blinded, prospectively randomized, controlled, pragmatic study. The pragmatic design allowing for a myriad of additional therapy approaches, and in particular - stepping up or down pharmaco- and psycho- therapy during the trial, as well as widely applicable inclusion and exclusion criteria, aims to answer previous concerns raised of the external validity of contemporary clinical HBO research.

Study Record Dates

• First Submitted: February 28, 2026
• First Posted: March 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

IL (1)