Circadian Integration of Photic and Non-photic Stimuli

Circadian rhythm disorders are disruptions in an individual's circadian rhythm, or "internal body clock." This internal clock regulates the 24-hour cycle of biological processes in the body, including sleep and hormone production. Jet lag, delayed sleep phase syndrome, in which individuals fall asleep and wake up later than desired, and advanced sleep phase syndrome, in which individuals fall asleep and wake up earlier than desired, are all examples of circadian rhythm disorders. Because of the disruptive nature of these conditions, it is important to identify the quickest and most effective method for regulating the body and reestablishing normal sleep patterns. Light therapy, in which individuals are exposed to bright, artificial light, is currently used to treat these disorders. Melatonin, a hormone that regulates circadian rhythms, and methylxanthines, a class of stimulant medications, are other common non-light treatments. While each of these individual treatments has been proven effective, little is known about the combined effect of light and non-light treatments. The purpose of this study is to evaluate the safety and effectiveness of light therapy, melatonin, and methylxanthine, alone and in combination, at regulating circadian rhythms and improving sleep quality and cognitive function.

This study will enroll healthy individuals. Participants will first attend two screening visits, which will include a review of medical, psychiatric, and sleep histories; vital sign measurements; blood and urine collection; a physical examination; and an electrocardiogram. For 1 week, participants will record sleep habits in a diary and by telephone. They will also wear a device that monitors activity and light exposure levels. Eligible participants will then attend four 5-day inpatient visits at the Sleep and Chronobiology Laboratory at the University of Colorado at Boulder. During each of the four visits, participants will be randomly assigned to one of the following four treatments:

• Dim light therapy and placebo
• Bright light therapy and placebo
• Dim light therapy, melatonin, and methylxanthines
• Bright light therapy, melatonin, and methylxanthines

At each visit, participants will receive a different treatment. During these visits, participants will remain awake for up to 40 hours at a time, while their eye movements, and brain, muscle, heart, and breathing activity are monitored. Urine and saliva will be collected, and participants will undergo various cognitive performance testing measures. At 3-week intervals between each visit, participants will record sleep habits and will wear the activity and light exposure monitoring device. A sleep diary will also be maintained by participants for 3 weeks following the end of the last visit.