0841 Morning Bright Light Therapy Improves Sleep in Veterans with Traumatic Brain Injury: Interim Analyses of a Randomized, Placebo-Controlled Trial

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Abstract Introduction Traumatic brain injury (TBI) is associated with persistent sleep-wake dysfunction, including insomnia and circadian rhythm disruption, which can exacerbate functional outcomes. Present therapies to treat TBI-associated sleep-wake disturbances (e.g., cognitive behavioral therapy for insomnia) are limited by marginal efficacy, poor patient acceptability, and/or high patient/provider burden. Morning bright light therapy (MBLT) is a simple, cost-effective, home-based sleep intervention with pleiotropic effects spanning sleep, circadian realignment, cognition, and mood. Methods The present data represent an interim analysis of an ongoing randomized, placebo-controlled clinical trial in Veterans with TBI (n=70). Veterans were randomized 2:1 to either MBLT (n=48) or non-light sham (n=22) and engaged in 60-minutes per day (within 2-hours of waking) to either device (MBLT; 10,000lux) for 4-weeks. Before the intervention, a 2-week baseline of sleep-wake recording was established. Primary outcomes include self-reported sleep, mood, cognition, and quality of life, as well as objective assessments of sleep and cognition, via actigraphy and neuropsychological testing, respectively. Results The MBLT group demonstrated improved self-reported sleep (insomnia severity index scores, 14±20%), coinciding with increased time in bed (59±67min), earlier sleep-onset (77±125min), and earlier mid-sleep time (37±72min), suggestive of circadian phase advancement. Self-reported cognition as well as short-term working memory (via the Hopkins Verbal Learning Test and the digit span test) both improved following MBLT, with concomitant improvements in mood, depression, and quality of life. Significant associations were found when considering PTSD or those with comorbid TBI, PTSD, and chronic pain (polytrauma clinical triad) as covariates. Plasma-based biomarkers also showed significant improvement in a sub-sample of n=20 MBLT participants, with reductions in ~20 proinflammatory cytokines, several pro-thrombotic clotting factors, and relevant neurodegenerative markers (e.g., pTau-217). There were no changes in the sham group. Conclusion MBLT is a feasible and highly acceptable home-based intervention to improve sleep and quality of life in Veterans with TBI. Additional work is needed to explore the therapeutic potential for MBLT in Veterans with either comorbid PTSD or the polytrauma clinical triad. Improvements in sleep likely contributed to downstream improvements observed in mood, depression, cognition, and pain management. This ongoing trial will serve as important scientific precedent for future work. Support (if any) CNRM-309698-7.01-65310, VA-I01-RX004822, HT9425-25-1-0895

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