This two-year study is designed to treat the neurocognitive, emotional/behavioral and psychosocial impairment in veterans who suffer from a combination of chronic, mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). The primary goal of this study is to demonstrate that positive changes in the psychosocial functioning of mTBI-PTSD veterans can be produced by a transcranial light therapy designed to help restore the cellular functioning of injured brain cells. The assumption underlying the expected improvement in primary psychosocial domains is that treating the injured brain directly will produce a corresponding increase in the health and effectiveness of the brain systems responsible for modulating/regulating thought, behavior and emotions. Improved regulation of thought, behavior and emotions will in turn manifest as decreased clinical symptomatology and increased capacity for veterans to successfully fulfill their social, interpersonal and occupational roles. The transcranial light treatment in this study is an innovative, photomedicine therapy using red and near- infrared (NIR) light produced from FDA-cleared, non-thermal, light-emitting diodes (LEDs) that are applied directly to the scalp. The photons from these wavelengths of light penetrate through the porous bone structure of the skull to reach cells that have been injured by brain trauma. Cell surfaces in the brain have photochromophores that react to the photons of light and, once stimulated, subsequently start a cascade of processes within the damaged cells to reverse the impaired cellular activity. The model for LED therapy effects is based on findings of decreased, cellular mitochondrial functioning after traumatic brain injury in animals and humans. Mitochondria power cells by creating adenosine tri-phosphate (ATP); however, in damaged cells, a hypoxic state leads to compromised ATP production. Photons of red and NIR light, absorbed by mitochondria in damaged brain cells, prompt release of nitric oxide from cytochrome C Oxidase in the mitochondrial membranes of hypoxic cells. Reversing the hypoxic state improves the subnormal cellular activity---increased ATP is released into the cell; better cellular respiration and oxygenation results). Currently, no empirically-validated, clinical therapies exist that directly and non-invasively target traumatically injured brain cells. This study's long-term objective, and relevance to the VA mission, is to develop, refine, and empirically validate an effective intervention that could be disseminated throughout the VA to clinicians and researchers for treating and rehabilitating TBI-PTSD veterans in clinics and adjunctively, or alternatively, as self-administered, home-based therapy.
The specific aims of this application to RR&D's SPiRE program are to: 1) build on positive findings from our open-protocol case studies with civilian TBI-PTSD patients by examining efficacy of transcranial LED therapy in a larger sham-controlled, clinical trial with veterans, and 2) use the findings as a bass for a future MERIT Review grant submission. Hypotheses: H1) at Post-treatment, the Real-LED compared to Sham-LED treatment, will produce significant improvement in: a) psychosocial functioning for measured domains of primary daily activity, b) neurocognitive measures of attention, memory, and executive function, and c) PTSD symptom severity; H2) effects detected at post- treatment will be maintained at 2-months; and H3) measured changes and self-reported treatment effects will be corroborated by the reports of knowledgeable collaterals. Study Design & Methods: Forty, mTBI+PTSD veterans, ages 18-55, will be enrolled over 2 years into a completely within-subjects design with a sham- controlled lead-in (Sham-LED Tx. before Real-LED Tx.) and four measurement times: Pre-Tx.; Post-Sham LED; Post-Real LED; 2-Mo. Follow-up. Measurement will include: assessment of daily psychosocial functioning (self-& others-report); PTSD, depression, pain, and neurocognitive domains (attention, memory and executive functioning. Power at alpha = .01 is adequate: Cohen's effect size=0.4 for all main effects.
At present, a very practical need exists for VA researchers to develop, validate and share new approaches for treating impaired functioning in veterans with chronic, mild TBI (mTBI) and post-traumatic stress disorder (PTSD). These two conditions commonly occur together in veterans who do not recover fully from concussions, and, in combination, they can cause marked disruption in thinking, managing emotions, social behavior, intimate relationships and working effectively at a job or in school. While PTSD treatments exist, the effects of the chronic brain injury can limit the benefits gained from these therapies. Proven treatments are needed that directly increase the functioning of injured brain cells, and parts of the brain involved in thinkig, emotions, behavior and our daily activities. This study will use a safe photomedicine treatment---red and near-infrared light applied to the head, to deliver photons that help repair the cellular activity of injured brain cells. We expect this therapy to reduce symptoms caused by PTSD and mTBI and improve daily functioning for veterans.