Efficacy of Ramelteon on Insomnia Symptoms Associated With Jet Lag in Healthy Adult Volunteers
Condition: Circadian Dysregulation
MeSH terms: Chronobiology Disorders; Jet Lag Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Ramelteon; Ramelteon; Ramelteon; Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Ramelteon 1 mg, tablets, orally, once nightly for 4 nights.; Ramelteon 4 mg, tablets, orally, once nightly for 4 nights.; Ramelteon 8 mg, tablets, orally, once nightly for 4 nights.; Ramelteon placebo-matching tablets, orally, once nightly for 4 nights.
Other intervention name(s): TAK-375; Rozerem™; TAK-375; Rozerem™; TAK-375; Rozerem™
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Circadian Rhythm Disorders; Biological Clock Disturbances; Jet Lag Syndrome; Time Zone Change Syndrome; Drug Therapy