Hyperbaric oxygen therapy as a potential treatment for post-traumatic stress disorder associated with traumatic brain injury

Figures & data

Table 1 Clinical trials using hyperbaric oxygen therapy for the treatment of brain injury or psychological disorders

Clinical trial identifier	Sponsor	Study type	Disease-specific treatment	Planned enrollment	Age (years)	Timing	Follow-up	Status
Acute severe TBI
NCT00170352	Minneapolis Medical Research Foundation	Ph2-R-OL	Acute severe TBI	80	16–65	3×1.5 ATA +3 h 100% O2 at 1.0 ATA vs no treatment	6 months	Completed; potential therapeutic efficacy, reduced mortality^Citation38
NCT02407028	Minneapolis Medical Research Foundation	Ph2-R-OL	Acute severe brain injury	200	16–65	≥5×2.0 ATA (no NBH), 2.5 ATA (no NBH), 1.5 ATA + NBH, 2.0 ATA + NBH, 2.5 ATA + NBH, 2/day 1.5 ATA, 2/day 2.0 ATA, 2/day 2.5 ATA, 2/day 1.5 ATA + NBH, control	6 months	Not open for recruitment
Chronic mild to severe TBI
NCT00594503	Harch	Ph1-NR-OL	Chronic mild, moderate, or severe TBI (+SPECT brain imaging and neuropsychological cognitive testing)	45	Children to adult	NP	NP	Recruiting
NCT01847755	Jupiter Medical Center	Ph1/2-NR-OL	Chronic mild to severe TBI	100	≥18	120×1.5 ATA/60 min	3 months	Recruiting
NCT02452619	Assaf-Harofeh Medical Center	PH1-NR-OL	Chronic mild to severe TBI + MRIs	30	≥18	50–70×1.5 ATA/60 min	3 months	Recruiting by invitation
NCT00592891	Harch	Ph1-NR-OL	Oxygen toxicity in chronic brain injury	45	Pediatric to adult	NP	NP	Recruiting
Chronic mild to moderate TBI/PTSD
NCT00760734	Harch	Ph1-NR-OL	Chronic mild to moderate TBI/PCS/PTSD	30	18–65	40 or 80×1.5 ATA/60 min; 2× day	30 days to 6 months after last dose	Completed; preliminary data (16 male patients), safe and improves symptoms, etc.; based on 5-day follow-up^Citation40
NCT01105962	International Hyperbaric Medical Foundation/Harch	Ph1-NR-OL	Chronic mild to moderate TBI/PCS/PTSD	133–1,000	18–65	40, 60, 80 at 1.5 ATA	2 years	Stopped by sponsor/IRB (funding issues)
NCT00810615	San Antonio Military Medical Center	Ph1/2-R-SB (s)	Chronic mild to moderate TBI	50	19–60	30×(3×2.4 ATA/30 min +2.4 ATA air/10 min) vs 30× air at <1.3 ATA/120 min	6 weeks	Completed; no reported results
Chronic mild TBI
NCT00830453	Intermountain Health Care	Ph2-NR-OL	Chronic mild brain injury (TBI/stroke/anoxia) (GCS ≥13)	60	18–80	60×1.5 ATA/60 min	Up to 6 months	Completed; safe and feasible; no clinically important improvement, though patients say otherwise^Citation41
NCT01126515	Intermountain Health Care, Inc.	Ph2-NR-OL	Chronic mild brain injury (GCS ≥13)	20	18–80	60×1.5 ATA/60 min	2 weeks	Completed; no reported results
NCT00715052	Assaf-Harofeh Medical Center	Ph1-R-SB(i)	Chronic mild TBI	60	>16	40×1.5 ATA/60 min or no treatment (control crosses over after follow-up)		Completed; safe and feasible, cognitive improvements observed^Citation42
NCT01220713	Virginia Commonwealth University	Ph2-R-DB	Chronic mild TBI (due to blast injury)	60	19–60	40×1.5 ATA (75% O2)/60 min, 40×2 ATA/60 min, 40× sham-air of 10.5% O2/60 min; all performed at 2 ATA	Up to 3 months	Completed; no reported results
NCT01611194	US Army Medical Research and Materiel Command	Ph2-R-DB	Chronic mild TBI	72	18–65	40×1.5 ATA/60 min or 1.2 ATA (21% O2)/60 min	4 years	Not currently recruiting
Chronic mild TBI and PTSD
NCT01306968	US Army Medical Research and Materiel Command	Ph2-R-DB	Chronic mild TBI/PCS/PTSD	79	18–65	40×1.5 ATA/60 min or 1.2 ATA (25% O2)/60 min or no intervention (PCS or [PTSD but no TBI])	70 days	Completed; male bias; no difference between 1.2 ATA (25% O2) and 1.5 ATA, both improved compared to no new intervention groups^Citation57
NCT01986205	Intermountain Health Care, Inc.	Ph2-R-DB	Chronic mild TBI/PCS	90	18–60	40×1.5 ATA/60 min vs 1.2 ATA (air) vs 1.0 ATA (air)	12 months	Not open for recruitment
NCT02089594	Louisiana State University/Harch	Ph3-R-SB(i)	Chronic mild TBI/PCS	100	18–65	40×1.5 ATA/60 min vs no HBOT (control group will receive HBOT after follow-up)	2 months	Recruiting
Other brain disorders including CO poisoning, cerebral palsy, and autism
NCT00596180	Harch	Ph1-NR-OL	Chronic CO poisoning + SPECT	40	NP	NP	NP	Recruiting
NCT00290186	Dayton Children’s Hospital	Ph1-R-DB	Cerebral palsy	49	3–8	40×1.5 ATA/60 min vs 1.5 ATA (14% O2)/60 min	6 months	Stopped by sponsor; no benefit observed^Citation56
NCT01925963	Intermountain Health Care, Inc./US Army Medical Research and Materiel Command	Ph1-NR-OL	Normal patients to act as normative datasets	75	18–65	No treatment	6 months	Not currently recruiting
NCT00324909	International Hyperbarics Association	Ph1-NR-OL	Autism	18	2–18	40×1.5 ATA/45 min vs 40×1.3 ATA (24% O2)/45 min	10 weeks	Completed; male bias; both groups showed reduced inflammation and improvement^Citation52
NCT00335790	International Hyperbarics Association	Ph1-R-DB	Autism	60	2–7	40×1.3 ATA (24% O2)/1 h vs 40×1.03 ATA (21% O2)/1 h	4 weeks	Completed; significant improvements observed^Citation51
NCT00406159	Thoughtful House	Ph1-R-OL	Autism	30	2–10	40×1.3 ATA (24% O2)/90 min	5 months	Completed; no consistent effects on the behavior of 16 patients^Citation63
NCT00670891	Vachira Phuket Hospital	Ph1-NR-OL	Autism	7	5–9	10×1.3 ATA	1 month	Completed; 75% of patients showed improvement in five domains^Citation62
NCT00263367	International Child Development Center	Ph1-NR-OL	Autism	10	5–12	1.3 ATA for 60 min; levels of blood glutathione and lipid peroxides measured before and after	1 h	Completed; no reported results
NCT00584480	University of California, San Francisco	Ph3-NR-OL	Autism	10	3–8	2×40×1.5 ATA/60 min	20 weeks	Completed; 2-point increase in CGI-I scale^Citation61
NCT02085330	Assaf-Harofeh Medical Center	Ph1-R-SB(o)	Mild cognitive impairment/vascular subcortical ischemia	60	65–90	2 ATA/90 min vs standard treatment; crossover	3 months	Recruiting
HBOT for preconditioning
NCT008177791	Xijing Hospital	Ph1-R-SB(c)	HBOT preconditioning against brain/heart injury during CABG surgery	49 (male)	<80	70 min for 5 days before coronary artery bypass grafting (CABG)	7 days	Completed, cerebral and cardiac protection observed after on-pump CABG^Citation155

Note: Unless stated otherwise ATA is at 100% oxygen.

Abbreviations: Ph1, Phase 1; Ph2, Phase 2; NR, nonrandomized; R, randomized; OL, open label; SB, single blind; (i), investigator; (s), subject; (c), caregiver; (o), outcome assessor; DB, double-blind; TBI, traumatic brain injury; GCS, Glasgow Coma Scale; SPECT, single-photon emission computed tomography; PCS, persistent concussive syndrome; PTSD, post-traumatic stress disorder; NP, not provided; ATA, absolute atmospheres; NBH, normobaric hyperoxia (high oxygen exposure at normal air pressure); CGI-I, Clinical Global Impression Scale – Improvement; h, hours; min, minutes.

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