By Xavier A. Figueroa, Ph.D.
A study was published recently under the sponsorship of the U.S. Army. This study, called HOPPS (Hyperbaric Oxygen Therapy for Persistent Post-Concussion Syndrome After Mild Traumatic Brain Injury)  published (Nov 17th, 2014), has received wide ranging reporting and (to my untrained eye) a media blitz for a small scale clinical trial. But, invariably, news only garners eyeballs when you sell the controversy (you can tell the story after the headline).
The headlines of the news articles reporting on the study have repeated a mischaracterization of the outcomes of HOPPS (see here, here, here and here), touting HBOT produces a placebo effect in mild traumatic brain injury (mTBI) study subjects (‘Treatment No Better Than Placebo for Post-concussion Symptoms’).
First, the authors of the study  concluded the following (our highlights):
“Our results support the conclusion that supplemental administration of breathing 100% oxygen at 1.5ATA(HBO procedure) or air at 1.2 ATA (sham procedure) for 60 minutes is well tolerated and improves symptoms and quality of life compared with local care management of PCS without chamber intervention.” [Bolding of the quote is ours]
“It has been argued that the sham designs used in this trial and other Department of Defense studies are not inert and represent dose-ranging trials of pressurized air. We recognize that a sham is not inert, and we cannot completely discount the physiological effects of minimal increases in nitrogen or oxygen from pressurized room air.”
The authors readily admit that HBOT (defined as breathing 100% Oxygen at 1.5 atmospheres absolute [ATA]) and pressurized air have an effect on mTBI study subjects, compared to the best care that member of the active armed service can receive. Furthermore, one of the treatment comparators (the pressurized air control) might actually not be as good a control as they had thought (the pressurized air “sham”).
So, I was a bit taken aback when I read the following sentences in the discussion and conclusion sections,
“However, we observed no difference between HBO and sham. We postulate that improvement in the chamber intervention groups was due to placebo effects or the potential benefit of daily interactions with the study staff….Taken with results from other concurrent investigations, our study does not support phase 3 trials of HBO for the treatment of PCS at this time.”
Now, authors can conclude anything they want with their results and if the results leave room for interpretation, well, you have to give it your best shot at interpreting.
My problem with the discussion and conclusion are the following:
- The treatment arms (pressurized air and HBOT) both showed superior outcomes in the primary measures they used (See Figure 1). Not only superior, but clinically and statistically significant than the best treatment the US Army can provide their wounded troops.
- The recognition that one of the supposed controls was not a control.
- The fact that two other DoD/VA sponsored studies recruiting wounded active duty members and one civilian-funded study on Marine veterans showed improvements in the same primary outcomes (symptoms for TBI and PTSD; Figure 1). That’s a total of 4 phase 1 clinical studies that showed improvements in at least 1 primary outcome and secondary outcomes.
- At least 2 phase 1 studies in a civilian population (Table 1) that support the effects of HBOT on symptoms and cognitive performance of study subjects.
- Concluding that (in essence): There is nothing of importance to see here. Move along. We recommend that no more research with HBOT be done for TBI/PCS.
Ordinarily, this would be a snoozer.
Unfortunately, the stakes are very high for the military service members that live with mTBI/PCS or have a misdiagnosis of PTSD  (see our previous post here). At a minimum, 22+ service members commit suicide  per day, mental health issues are presumed to be the primary drivers of the suicide (PTSD and TBI). The Institute of Medicine of the National Academy of Science concluded that the DoD and VA have spent $9.2 billion attempting to deal with PTSD , but unable to stop the suicide epidemic (this study briefly mentions HBOT as a potential treatment option (p. 263) for TBI, but makes no conclusions or recommendations regarding its use for PTSD).
This is a bit of a poser for physicians. Currently, there are no phase III clinical trials that have tested the efficacy of TBI/PCS and PTSD treatments that are currently in use by VA and DoD medical. Yet, the routine prescription of drugs and therapies occurs daily. So, if a doctor wants to try HBOT for his/her patients within the Armed Services, they have to move Heaven and Earth to get the treatment for their patients. This may include getting creative in how their patients get treatment, including begging civilian groups to sponsor treatment …but that is another story entirely.
This directly affects the civilian health care space, when it comes to treatment for mTBI/PCS. Medical groups, associations and insurance groups are unlikely to cover HBOT treatments for this type of neurological injury. The published reports can be used as justification for denying payment or treatment. This ensures that only those willing or able to pay (or provided pro bono) for treatment will receive HBOT.
Significantly, these reports make the pursuit of further research much harder. Funding agencies are unlikely to provide research money when the assumption of non-efficacy is so widely broadcast. Convincing other scientists and medical researchers that there is a case for using HBOT for neurological conditions then becomes an uphill battle.
This fight is far from over, but it should be unnecessary.
The cardinal rule in Medicine is
“First, Do No Harm.”
The second rule should be
“Work to Restore Health.”
If a treatment has few side effects (HBOT is safe and well tolerated [1,5,6,7,8,9,10,11,12,13] and good preliminary evidence for its use, the physician has the right and obligation to prescribe it. Other unproven treatments are applied regularly and covered.
But delay has costs to a society.
Veterans and active duty members will continue to take their lives.
Individual groups will try to find treatments for loved ones, without the help of those that should be aiding them.
People will lose faith and hope in the institutions that are charged with caring and protecting them.
And so it goes…
The fight goes on for brain health and healing.
|Figure 1- Primary outcomes of HBOT trials for mTBI/PCS treatment in armed service personnel and veterans.|
- Miller RS, Weaver LK, Bahraini N, Churchill S, Price RC, et al. (2014) Effects of Hyperbaric Oxygen on Symptoms and Quality of Life Among Service Members With Persistent Postconcussion Symptoms: A Randomized Clinical Trial. JAMA Intern Med.
- MacGregor AJ, Shaffer RA, Dougherty AL, Galarneau MR, Raman R, et al. (2010) Prevalence and psychological correlates of traumatic brain injury in operation iraqi freedom. J Head Trauma Rehabil 25: 1-8.
- Kemp J, Bossarte R (2012) Suicide Data Report, 2012 In: Department of Veterans Affairs MHS, Suicide Prevention Program, editor: Office of Public and Intergovernmental Affairs.
- (IOM) IoM (2014) Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Final Assessment. Washington, DC: National Academy of Science.
- Cifu DX, Walker WC, West SL, Hart BB, Franke LM, et al. (2014) Hyperbaric oxygen for blast-related postconcussion syndrome: Three-month outcomes. Ann Neurol 75: 277-286.
- Cifu DX, Hart BB, West SL, Walker W, Carne W (2014) The effect of hyperbaric oxygen on persistent postconcussion symptoms. J Head Trauma Rehabil 29: 11-20.
- Rockswold SB, Rockswold GL, Zaun DA, Liu J (2013) A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury. J Neurosurg 118: 1317-1328.
- Churchill S, Weaver LK, Deru K, Russo AA, Handrahan D, et al. (2013) A prospective trial of hyperbaric oxygen for chronic sequelae after brain injury (HYBOBI). Undersea Hyperb Med 40: 165-193.
- Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, et al. (2013) Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury – Randomized Prospective Trial. PLoS One 8: e79995.
- Wolf G, Cifu D, Baugh L, Carne W, Profenna L (2012) The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma 29: 2606-2612.
- Harch PG, Andrews SR, Fogarty EF, Amen D, Pezzullo JC, et al. (2011) A Phase I Study of Low-Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post-Concussion Syndrome and Post-Traumatic Stress Disorder. J Neurotrauma.
- Gossett WA, Rockswold GL, Rockswold SB, Adkinson CD, Bergman TA, et al. (2010) The safe treatment, monitoring and management of severe traumatic brain injury patients in a monoplace chamber. Undersea Hyperb Med 37: 35-48.
- Wright JK, Zant E, Groom K, Schlegel RE, Gilliland K (2009) Case report: Treatment of mild traumatic brain injury with hyperbaric oxygen. Undersea Hyperb Med 36: 391-399.