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Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag

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ClinicalTrials.gov Identifier: NCT00097474
Recruitment Status : Completed
First Posted : November 24, 2004
Last Update Posted : September 14, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Tracking Information
First Submitted Date  ICMJE November 23, 2004
First Posted Date  ICMJE November 24, 2004
Last Update Posted Date September 14, 2021
Actual Study Start Date  ICMJE December 21, 2004
Actual Primary Completion Date January 6, 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
improvement in jet lag symptoms [ Time Frame: 10 days ]
Patients will report jet lag symptoms via questionnaire
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
salivary cortisol level [ Time Frame: 10 days ]
salivary cortisol at bedtime will be measured
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag
Official Title  ICMJE The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet Lag
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Jet Lag
Intervention  ICMJE
  • Drug: Hydrocortisone
    Hydrocortisone will be given alone or in combination with Melatonin to see if symptoms of jet lag are alleviated
  • Drug: Melatonin
    Melatonin will be given alone or in combination with Hydrocortisone to see if symptoms of jet lag are alleviated
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Combination
    Both HC 30 and ML 5 will be administered
    Interventions:
    • Drug: Hydrocortisone
    • Drug: Melatonin
  • Experimental: Hydrocortisone
    30mg Hydrocortisone will be administered
    Intervention: Drug: Hydrocortisone
  • Experimental: Melatonin
    5 mg Melatonin will be administered
    Intervention: Drug: Melatonin
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2009)
57
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
60
Actual Study Completion Date  ICMJE November 14, 2007
Actual Primary Completion Date January 6, 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • Age greater than or equal to 18, but less than or equal to 65, men or women.
  • Normal physical exam and laboratory results.
  • Negative urinary pregnancy test 1 week prior to travel (pre-menopausal women).
  • Planned non-stop eastward flight crossing 6-8 time zones between 30n and 50n latitudes.
  • A minimum stay of 4 - 10 days abroad.
  • Willingness and anticipated ability to comply with study procedures, including sleep and wake hours, saliva collection and questionnaire completion.
  • Written informed consent.

EXCLUSION CRITERIA:

  • BMI less than or equal to 20 or greater than or equal to 30 kg/m.
  • Current psychiatric or seizure disorder.
  • Current sleep disorder as assessed by presence of sleep apnea, daytime napping of more than 20 minutes, chronic fatigue.
  • History of Cushing's syndrome.
  • Serious chronic medical condition.
  • Current drug or alcohol abuse.
  • SGOT or SGPT greater than three-fold normal.
  • Current pregnancy or lactation.
  • Current use of CPAP.
  • Chronic use of beta-blockers (which inhibit melatonin secretion), anti-epileptic agents, anticoagulants, fluvoxamine, nifedipine or soporific or sleep-inducing agents (including benzodiazepines, melatonin), or glucocorticoids (including nasal or inhaled steroids).
  • Fasting blood glucose greater than 110 mg/dL or known diabetes.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00097474
Other Study ID Numbers  ICMJE 050037
05-CH-0037
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lynnette K Nieman, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date February 12, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP