0845 Actigraphy-Masured Sleep Is Improved After Dietary Supplementation in Older Adults with Mild Traumatic Brain Injury: A Randomized Clinical Trial

Abstract Introduction Sleep-wake disturbances are strongly associated with traumatic brain injury (TBI) and frequently persist into the chronic recovery phase. Clinical interventions to improve these disturbances are limited, being symptom-directed or with excessive patient-provider burden. Preclinical work in a rodent model of TBI show that dietary supplementation with branched-chain amino acids (BCAA: leucine/isoleucine/valine) restores a normal sleep-wake phenotype, mechanistically via restoring orexin/hypocretin input in the lateral hypothalamus. The present data reflect the field's first effort at translating these preclinical data to humans in a large-scale, double-blinded, placebo-controlled clinical trial. Methods Veterans with TBI (n=175 enrolled) were randomized via covariate adaptive randomization and n=160 allocated (1:1:1:1) to high (30g b.i.d.), medium (20g b.i.d.), and low (10g b.i.d.) BCAAs or placebo (rice protein, 10g b.i.d.) for 12 weeks. Actigraphy was continuously recorded. The effect of BCAAs (group) on total sleep time (TST), sleep-onset-latency (SOL), wake-after-sleep-onset (WASO), sleep efficiency (SE), and awakenings was examined using linear models. All models were adjusted for sex, age, PTSD, depression, TBI recency, and pain. Participant ID was included as a random factor to account for repeated measures. Results 154 age- and sex-matched (49±10 years of age, 73% male) Veterans with TBI were analyzed: placebo (n=36), low (n=40), medium (n=35), and high (n=43) dose groups. Participants in the high-dose group demonstrated an increase in TST of 0.66 minutes/day (~55min over 84-days, p< 0.001), a decrease in WASO of 0.21 minutes/day (~17.6min over 84-days, p< 0.001), and an increase in SE of 0.05% per day (~4.2% over 84-days, p=0.01) compared to placebo. Effects in the medium- and low-dose groups were less robust, with both showing an increase in SE compared to placebo (medium: ~5.0% over 84-days, p< 0.001; low: ~3.4% over 84-days, p=0.03), and only the low-dose group showing a decrease in WASO compared to placebo (~18.5min over 84-days, p< 0.001). No changes were present in SOL or awakenings. Conclusion Dietary BCAA supplementation at 60g/day improves objective metrics of sleep in Veterans in the chronic phase of recovery from TBI. Future and ongoing work will examine changes in spectral power during sleep and cognitive function. Support (if any) VA-BLRD-IK2-BX002712, VA-RRD-RX004822