This sham-controlled study will investigate if scalp application of non-invasive, light-emitting diodes (LED) in red and near-infrared (NIR) wavelengths improves cognition in Veterans with Gulf War Veterans' Illnesses (GWVI). Impaired cognition is one of the 3 major symptom areas of GWVI. Pilot data show that scalp application of red/NIR LEDs significantly improves cognition in chronic, traumatic brain injury (TBI), including improvement in Executive Function (multi-tasking, processing speed) and Memory. Pilot data show increased rCBF on functional MRI scans after a series of red/NIR LED treatments in chronic stroke; and neurodegenerative disease, Primary Progressive Aphasia (similar to Alzheimer's Disease). There is improved mitochondrial function with increased production of adenosine tri-phosphate (ATP) in hypoxic/compromised cells treated with red/NIR photons. Mitochondrial dysfunction is reported in GWI Veterans; associated with neurotoxicant exposures during deployment [organophosphate pesticides (OP); and pretreatment nerve agents, pyridostigmine bromide (PB) pills]. Design: This is a blinded, Sham-controlled study. All participants receive a series of Sham, followed by a series of Real LED treatments. Method: Participants will be Veterans originally deployed from Ft. Devens, MA, who have previously participated in GWI surveys and have agreed to be re-contacted. Dr. Krengel, Co-Investigator, has a DoD grant (2011-2014) to re-survey these Veterans via web survey. She will review the web data and refer cases to this LED study who meet CDC multi-symptom illness criteria (Fukuda et al., 1998) for GWVI: one chronic symptom (>6 months) in at least 2 of 3 categories: 1) musculoskeletal pain; 2) mood-cognition; 3) fatigue. Participants must report cognitive problems, and at least one other symptom of GWVI. Further screening with additional Neuropsychological (NP) tests will be performed. This is a 4-year study, with 40 cases treated per year, total=160. Primary Outcome Measures are NP testing in 3 domains: 1) Attention/Executive Function; 2) Learning and Memory; 3) Psychomotor/Visual Spatial. Secondary Outcome Measures include pain; fatigue; mood; and biomarkers from blood tests (mitochondrial function, inflammation, coagulation, and general health). Treatment: A Real LED helmet and identical Sham LED helmet will be used. LEDs are FDA-cleared, non-significant risk. During all treatments the patient wears goggles that block red wavelength; NIR wavelength is beyond the visible spectrum. Participants have NP testing at Entry and 1 blood draw; 15 Sham LED Tx's (2x/Wk; 7.5 Wks) and within 1 week post- 15th Sham Tx, NP and 1 blood draw. Then, 15 Real LED Tx's (2x/Wk; 7.5 Wks) and within 1 week post- 15th Real Tx, NP and 1 blood draw; maintenance NP testing 2 mo. later. Interim analyses are planned at halfway point of study, with the O'Brien-Fleming alpha spending function to establish stopping boundaries to be conservative. If MANOVA is significant at p<.022, efficacy will be considered to be reliably established. Power = .93 to detect significant within-Subject change from Baseline (or from end of Sham) to end of Treatment, interim analyses.
Impaired cognition is one of the 3 major symptom areas of Gulf War Veterans' Illnesses (GWVI). This sham- controlled study will investigate if scalp application of painless, non-invasive, light-emitting diodes (LED) in red and near-infrared (NIR) wavelengths improves cognition in veterans with GWVI. Our pilot data show that scalp application of red/NIR LEDs significantly improves cognition in chronic, traumatic brain injury. Our data also show increased regional cerebral blood flow (rCBF) on functional MRI scans after red/NIR LED treatments in chronic stroke. Increased rCBF is triggered by release of nitric oxide from hypoxic/compromised cells, after exposure to the red/NIR photons. Red/NIR photons also promote improved mitochondrial function and increased production of adenosine tri-phosphate (ATP). GWI veterans have mitochondrial dysfunction due to neurotoxicant exposures. This will be the first study to investigate a science- and evidence-based treatment expected to improve cognition in veterans with GWVI. Treatment of these 200,000 veterans is a high priority.
