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Efficacy of Ramelteon on Insomnia Symptoms Associated With Jet Lag in Healthy Adult Volunteers

Phase 4
Completed
Conditions
Circadian Dysregulation
Interventions
Drug: Placebo
Registration Number
NCT00492011
Lead Sponsor
Takeda
Brief Summary

The purpose of this study to determine the degree to which ramelteon, once daily (QD), can reduce the insomnia symptoms associated with rapid, eastward travel across 5 time zones.

Detailed Description

Circadian dysrhythmia, or jet lag, is defined as multiple biologic and psychologic stresses created by rapid travel across multiple time zones. As more people are transported by jet aircraft, the issue of jet lag becomes more important. What was an inconvenience during travel for leisure is now a physiologic consequence for the travelers and crew.

Jet lag is composed of a variety of unpleasant symptoms that vary with the number of time zones crossed, the individual, and even the direction flown (east versus west). The most typical symptoms include daytime sleepiness, fatigue, impaired alertness, and trouble initiating and maintaining sleep. Other symptoms of circadian dysrhythmia are insomnia, gastrointestinal complaints, apathy, weakness, irritability, malaise, and loss of appetite. Travel across time zones also has been associated with diabetic ketoacidosis, depression, and impaired cognitive performance in individuals at risk. Decreased sport performance has been noted in several studies.

In addition to environmental and social cues, physical factors, such as age, hydration status, and illness, could adversely affect the ability to entrain (adjust) quickly. The stressors of flight, noise, vibration, decreased humidity, barometric pressure changes, and decreased partial pressure of oxygen all contribute to crew and travelers health at the destination.

Being out of synchronicity with the environment causes jet lag symptoms. Travel through time zones places the body in a situation when it must sleep when not tired and awaken when the internal cues are initiating sleep. The brain's internal clock is the suprachiasmatic nucleus within the hypothalamus the body is in a constant state of circadian adjustment to remain entrained to a given time zone. In addition to the subjective feeling of well being are measurable changes associated with daily patterns. For example, core body temperature changes throughout the day and decreases before falling asleep. Melatonin levels increase in the evening and night and recede during the day.

Ramelteon is a melatonin receptor 1 and melatonin receptor 2 agonist currently marketed in the US for the treatment of insomnia characterized by difficulty with sleep onset. Study participation is anticipated to be about 2 weeks.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
110
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ramelteon 1 mg QDRamelteon-
PlaceboPlacebo-
Ramelteon 4 mg QDRamelteon-
Ramelteon 8 mg QDRamelteon-
Primary Outcome Measures
NameTimeMethod
Average Latency to Persistent Sleep measured by polysomnography.Nights 2, 3, and 4
Secondary Outcome Measures
NameTimeMethod
Dim light melatonin offset time in a subset of subjects defined as the time of the morning when the melatonin drops to below 3 pg/mL with a downward slope.Nights 2, 3, and 4
Total sleep time in minutes by polysomnography.Nights 2, 3, and 4
Number of awakenings after persistent sleep by polysomnography.Nights 2, 3, and 4
Wake time after persistent sleep onset by polysomnography.Nights 2, 3, and 4
Sleep efficiency by polysomnography.Nights 2, 3, and 4
Karolinska Sleepiness ScaleDays 1, 2, 3, 4 and 5
Pittsburgh Sleep Quality IndexDay 6
Daytime Function measured by Daytime Function Questionnaire (DTFQ) and Psychomotor Vigilance test (PVT)Day 3
Digit Symbol Substitution TestDays 1, 2, 3, 4 and 5
Memory Recall TestDays 1, 2, 3, 4 and 5
Visual Analogue Scale for Mood and Feelings, level of alertness and ability to concentrateDays 1, 2, 3, 4 and 5
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