Improving Residual Sleepiness and Inflammation in Older Adults with OSA: An RCT of Citicoline

About This Grant

ABSTRACT Obstructive sleep apnea (OSA) is a leading public health problem, with estimates that one in 15 adults in the United States suffer from the condition. It is reported that up to 20%-40% of older adults have OSA. Of concern is that up to 34% of individuals treated with standard of care Continuous Positive Airway Pressure (CPAP) therapy have residual sleepiness despite normalization of breathing during sleep. The risk of death is more than two times higher in older adults with OSA and who struggle with excessive daytime sleepiness. The PI’s completed NIH R00 study determined that lower plasma choline and increased inflammation is associated with sleepiness in individuals diagnosed with OSA. A significant correlation between plasma levels of choline and the antioxidant enzyme Superoxide Dismutase-1 (SOD1), was also identified. Citicoline (a dietary, endogenous nutrient) is an oral choline supplement that is well-tolerated by users. Previous studies in animals have shown citicoline inhibits inflammatory cytokines such as Interleukin-6 (IL-6) and improves SOD1. These findings provide support for our theory that choline supplementation will inhibit inflammation and improve sleepiness. Existing wake promoting medications are limited by their tendency for dependency, adverse side effects, and contraindications of usage in those with cardiovascular comorbidities and in the elderly. Citicoline has the potential to improve residual sleepiness and reduce inflammation, yet this intervention has not yet been explored in the OSA population despite a need for improved symptom management. We hypothesize that the addition of citicoline to standard of care treatment (CPAP) will result in improvements in residual sleepiness and inflammation. We will conduct a 4-week randomized, double-blind, placebo-controlled clinical trial comparing citicoline versus placebo in 120 (60 in each group) individuals aged 55 years and older prescribed CPAP who have residual excessive daytime sleepiness [defined by an Epworth Sleepiness Scale (ESS) score of >=11] despite at least 3 months of effective, adherent CPAP use. Participants will be recruited from the Emory Sleep Center. The first aim is to determine whether the citicoline group shows improvements in residual sleepiness and plasma choline compared to the placebo group from T1 to T2. The second aim is to determine whether the citicoline group has increases in SOD1 levels and reductions in IL-6 compared to the placebo group from T1 to T2. Repeated assessments will consist of sleep, diet, and quality of life questionnaires, 2 nights of the Sleep Profiler PSG2 home sleep device, and 7 nights of wrist actigraphy. Our team has extensive experience with biomarkers, clinical research, and sleep medicine. Positive outcomes from this project will allow citicoline to be used as a new therapeutic to improve residual sleepiness and inflammation, which will lead to a reduction in OSA-related comorbidities and improve the health and well-being of older adults.