Efficacy of Ramelteon on Insomnia Symptoms Associated With Jet Lag in Healthy Adult Volunteers
|ClinicalTrials.gov Identifier: NCT00492011|
Recruitment Status : Completed
First Posted : June 27, 2007
Last Update Posted : February 28, 2012
|Condition or disease||Intervention/treatment||Phase|
|Circadian Dysregulation||Drug: Ramelteon Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Ability of Ramelteon 1 mg, 4 mg, and 8 mg to Alleviate the Insomnia Symptoms Associated With Eastward Bound Jet Lag Across 5 Time Zones in Healthy Adult Volunteers|
|Study Start Date :||February 2007|
|Primary Completion Date :||August 2007|
|Study Completion Date :||August 2007|
|Experimental: Ramelteon 1 mg QD||
Ramelteon 1 mg, tablets, orally, once nightly for 4 nights.
|Experimental: Ramelteon 4 mg QD||
Ramelteon 4 mg, tablets, orally, once nightly for 4 nights.
|Experimental: Ramelteon 8 mg QD||
Ramelteon 8 mg, tablets, orally, once nightly for 4 nights.
|Placebo Comparator: Placebo||
Ramelteon placebo-matching tablets, orally, once nightly for 4 nights.
- Average Latency to Persistent Sleep measured by polysomnography. [ Time Frame: Nights 2, 3, and 4 ]
- 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. [ Time Frame: Nights 2, 3, and 4 ]
- Total sleep time in minutes by polysomnography. [ Time Frame: Nights 2, 3, and 4 ]
- Number of awakenings after persistent sleep by polysomnography. [ Time Frame: Nights 2, 3, and 4 ]
- Wake time after persistent sleep onset by polysomnography. [ Time Frame: Nights 2, 3, and 4 ]
- Sleep efficiency by polysomnography. [ Time Frame: Nights 2, 3, and 4 ]
- Karolinska Sleepiness Scale [ Time Frame: Days 1, 2, 3, 4 and 5 ]
- Pittsburgh Sleep Quality Index [ Time Frame: Day 6 ]
- Daytime Function measured by Daytime Function Questionnaire (DTFQ) and Psychomotor Vigilance test (PVT) [ Time Frame: Day 3 ]
- Digit Symbol Substitution Test [ Time Frame: Days 1, 2, 3, 4 and 5 ]
- Memory Recall Test [ Time Frame: Days 1, 2, 3, 4 and 5 ]
- Visual Analogue Scale for Mood and Feelings, level of alertness and ability to concentrate [ Time Frame: Days 1, 2, 3, 4 and 5 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00492011
|United States, Florida|
|Miami, Florida, United States|
|Pembroke Pines, Florida, United States|
|United States, Hawaii|
|Honolulu, Hawaii, United States|
|United States, New York|
|New York, New York, United States|
|Study Director:||Medical Director Clinical Science||Takeda|