Effectiveness of Combining Light and Non-Light Treatments for Jet Lag and Sleep Disorders

Study Overview
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Brief Summary
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Jet lag and some sleep disorders are caused by a disruption in an individual's internal clock. Understanding the most effective way to quickly re-adjust the body's internal clock will be beneficial for treating individuals with these conditions. This study will evaluate the combined effectiveness of light and non-light therapies at regulating sleep cycles and improving sleep quality.

Detailed Description
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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.

Official Title
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Circadian Integration of Photic and Non-photic Stimuli

Conditions
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Sleep Disorders, Circadian Rhythm

Intervention / Treatment
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* Drug: Melatonin
* Drug: Methylxanthine
* Procedure: Light Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good general health, as determined by blood chemistries, urine toxicology, physical examination, and medical and psychiatric history Exclusion Criteria: History of any current or chronic disease, including any of the following: Chronobiologic disorders Sleep disorders Cardiovascular disorders Respiratory disorders Kidney and urinary tract disorders Infectious diseases Gastrointestinal disorders Immune system disorders Connective tissue and joint disorders Hematopoietic disorders Neoplastic diseases Endocrine and metabolic diseases Neurologic disorders Current or past history of drug abuse Pregnant or breastfeeding Current oral contraceptive use

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dim Light Melatonin and/or methylxanthine<br>Dim Light Melatonin and/or methylxanthine | Drug: Melatonin<br>* 5mg, pill, once<br>* Other names: Life Extension Melatonin 5 mg;Drug: Methylxanthine<br>* 2.9 mg/kg, pill, once<br>|
| Experimental: Placebo and Dim Light or bright light<br>Placebo and Dim Light or bright light | Procedure: Light Therapy<br>* Bright light exposure<br>|
| Experimental: Bright light melatonin and/or methylxanthine<br>Bright light, melatonin, and/or methylxanthine | Drug: Melatonin<br>* 5mg, pill, once<br>* Other names: Life Extension Melatonin 5 mg;Drug: Methylxanthine<br>* 2.9 mg/kg, pill, once<br>Procedure: Light Therapy<br>* Bright light exposure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circadian phase, as measured by the shift of the endogenous melatonin rhythm (measured during each inpatient visit) |  | 24 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circadian phase, as measured by the shift of the endogenous temperature rhythm |  | 24 hour | 
| Sleep quality, as measured by wakefulness after sleep onset (electroencephalogram [EEG] defined wakefulness after 10 minutes of consecutive sleep) and number of awakenings |  | overnight | 
| Cognitive function, as measured by daytime sleepiness, reaction time, and mood and well being (all measured during each inpatient visit) |  | 24 h and daytime | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circadian Rhythm Sleep Disorders