Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag
Condition: Jet Lag
MeSH terms: Jet Lag Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine the effects of cortisol (hydrocortisone), melatonin, a combination of
      cortisol and melatonin, and placebo (an inactive substance) on jet lag symptoms. Jet lag is a
      term used to describe symptoms people commonly experience after rapid travel across several
      time zones. The cause of jet lag is not known, but various hormones, including cortisol and
      melatonin, have a day-to-night pattern of secretion and play a role in maintaining the body's
      internal rhythms. This study will test whether taking cortisol, melatonin, or both can help
      re-establish the body's day-night cycle and result in less jet lag.

      People between 18 and 65 years of age who are planning a non-stop eastward flight with the
      following characteristics may be eligible for this study:

        -  Crossing six to eight time zones (6 to 8 hours difference between Eastern Standard Time
           and the destination)

        -  Destination between 30 and 50 latitudes (approximately Cairo to London)

        -  Evening flight (5 PM to midnight) with morning arrival

        -  Remaining abroad at least 4-10 days

      Candidates must have a body mass index (BMI) between 20 and 30 kg/M (not too thin and not
      overweight) and must not be taking medicines that affect sleep or cortisol or melatonin
      levels. Prospective participants are screened with a medical history, blood tests, and check
      of blood pressure, height, and weight.

      Pre-flight Procedures

      Participants keep a sleep journal 3 days before the flight. For 1 day within 3 days of the
      flight they fill out jet lag and sleepiness questionnaires and collect morning and bedtime
      saliva samples for measurement of cortisol and melatonin. The saliva is collected by chewing
      on two small cotton pads and spitting them into a tube. Premenopausal women provide a urine
      sample the week before the flight to test for pregnancy. On the day of the flight, the
      participants do not collect saliva or fill out sleep logs or questionnaires. They are given
      two bottles with study medication. One bottle, labeled "AM," contains either hydrocortisone
      or placebo; the other, labeled "PM," contains either melatonin or placebo.

      Post-flight Procedures

      Upon arriving at their destination in the morning, participants obtain a saliva sample and
      take one of the capsules in the "AM" bottle. At bedtime, they collect saliva and then take
      one of the "PM" capsules. They repeat the medication doses for a total of 4 days and repeat
      the saliva collections on days 2 through 4, 7 and 10 after arrival. In addition, participants
      complete jet lag and sleep questionnaires in the morning, afternoon, and just before bedtime
      on the day of arrival and on days 2 through 4, 7 and 10.

      After they return from their trip, participants are seen at the NIH Clinic to bring in their
      saliva specimens and review their questionnaires with study investigators.
    

Detailed description: 
      Jet lag resulting from rapid flight across several time zones is a common complaint of
      travelers. The symptoms of jet lag are primarily described as daytime sleepiness, fatigue,
      and impaired mental efficiency and can also include weakness and irritability. It is
      considered to be due to the desynchronization between the internal circadian rhythm and the
      new local day-night cycle at the traveler s destination. A means of rapidly resynchronizing
      the circadian rhythm to the local time would benefit people who suffer severely from this
      syndrome.

      What actually underlies jet lag is a question that has not been fully answered. Various
      endogenous hormones, including cortisol and melatonin, have a natural circadian rhythmicity
      and play a role in maintaining the body s internal clock. Cortisol is produced by the
      hypothalamic- pituitary-adrenal axis in a circadian manner and in response to stress. Normal
      cortisol has a diurnal rhythm with a maximum level in the morning and a nadir during the
      night. While a time shift does not change the total daily amount of cortisol that is
      secreted, the temporal organization of the cortisol secretions is disrupted and the circadian
      rhythm does not re-entrain for several days. Thus, the first few mornings in a new time zone
      can be considered relatively cortisol-deficient because the traveler does not experience the
      peak of cortisol at the time of awakening. Taking exogenous glucocorticoids at the proper
      time may help re-entrain the circadian rhythm faster and result in less jet lag.

      Melatonin is a hormone that is secreted nocturnally by the pineal gland. Exposure to bright
      light diminishes its release while darkness triggers it. A recent meta-analysis has shown
      that taking melatonin can alleviate symptoms of jet lag.

      The aim of the present study is an attempt for the first time to attenuate jet lag symptoms
      with hydrocortisone, melatonin, a combination of both hydrocortisone and melatonin or
      placebo.

      Forty-eight normal volunteers will be randomized in blocks of eight to one of four treatment
      arms: hydrocortisone (25 mg) alone, melatonin (5 mg) alone, hydrocortisone (25 mg) and
      melatonin (5 mg) in combination, and placebo. Volunteers will travel in an eastwardly
      direction across 6-8 time zones. Upon morning arrival at the new destination, volunteers will
      obtain a saliva sample and then take 25 mg hydrocortisone (or placebo). At the target bedtime
      of (10 pm to midnight local time) they will take 5 mg of melatonin (or placebo). Volunteers
      will wake up at 7 am-10:30 am (local time) and take 25 mg hydrocortisone (or placebo).
      Subjects will repeat these dosages for 3 days for a total of four days. Participants also
      will obtain salivary samples of cortisol and melatonin on awakening and at bedtime on one day
      before travel and at the new destination for days 1 - 4, 7 and 10 after arrival. The primary
      outcome measure will be subjective rating of jet lag and components or correlates of this
      such as fatigue and daytime tiredness. Subjects will keep sleep logs and fill out a symptoms
      questionnaire daily for 3 days before and 4 days after the flight and on days 7 and 10.
      Secondary outcomes will be the measurement of salivary cortisol and melatonin. The data
      obtained from this study will provide an assessment of effective treatment of jet lag
      syndrome and will provide a better understanding of the role of hormones in the disruption of
      the circadian rhythm.
    

Intervention name(s): Hydrocortisone; Melatonin; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Hydrocortisone will be given alone or in combination with Melatonin to see if symptoms of jet lag are alleviated; Melatonin will be given alone or in combination with Hydrocortisone to see if symptoms of jet lag are alleviated; Placebo
Intervention MeSH terms: Hydrocortisone; Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Cortisol; Jet Lag; Healthy Volunteer; HV