Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag

This study has been completed.
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) )
ClinicalTrials.gov Identifier:
NCT00097474
First received: November 23, 2004
Last updated: September 18, 2014
Last verified: August 2014
  Purpose

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.

...


Condition Intervention Phase
Jet Lag Syndrome
Drug: Hydrocortisone
Other: Placebo
Drug: Hydrocortisone and Melatonin
Drug: Melatonin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet Lag

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Fatigue score

Enrollment: 57
Study Start Date: November 2004
Study Completion Date: November 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydrocortisone
Upon morning arrival at the new destination, volunteers take 20 mg hydrocortisone and at the target bedtime of (10 pm to midnight local time) theywill take placebo for four days.
Drug: Hydrocortisone
Upon morning arrival at the new destination, volunteers take 20 mg hydrocortisone (or placebo) and at the target bedtime of (10 pm to midnight local time) they will take 5 mg of melatonin (or placebo) for four days.
Experimental: Melatonin
Upon morning arrival at the new destination, volunteers take 20 mg placebo and at the target bedtime of (10 pm to midnight local time) they willtake 5 mg of melatonin for four days.
Drug: Melatonin
N/A
Experimental: HC/Melatonin
Upon morning arrival at the new destination, volunteers take 20 mg hydrocortisone and at the target bedtime of (10 pm to midnight local time) theywill take 5 mg of melatonin for four days.
Drug: Hydrocortisone and Melatonin
Upon morning arrival at the new destination, volunteers take 20 mg hydrocortisone (or placebo) and at the target bedtime of (10 pm to midnight local time) they will take 5 mg of melatonin (or placebo) for four days.
Placebo Comparator: Placebo
Upon morning arrival at the new destination, volunteers take placebo and at the target bedtime of (10 pm to midnight local time) they will take placebo for four days.
Other: Placebo
Upon morning arrival at the new destination, volunteers take 20 mg hydrocortisone (or placebo) and at the target bedtime of (10 pm to midnight local time) they will take 5 mg of melatonin (or placebo) for four days.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Age greater than or equal to 18, but less than or equal to 65, men or women.
  • Normal blood pressure, BMI within 20-30 and normal 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.
  • Exclusion of individuals who have not experienced jet lag on previous flights.
  • Use of medications known to interact with melatonin or hydrocortisone.
  • Use of prescription, over-the counter, or alternative medications known to cause sleep disturbances.
  • Use of prescription, over-the counter, or alternative medications that commonly cause insomnia or excessive drowsiness.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00097474

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Lynnette K Nieman, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT00097474     History of Changes
Other Study ID Numbers: 050037, 05-CH-0037
Study First Received: November 23, 2004
Last Updated: September 18, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cortisol
Travel
Saliva
Body Clock
Sleep
Healthy Volunteer
HV
Jet Lag

Additional relevant MeSH terms:
Jet Lag Syndrome
Chronobiology Disorders
Nervous System Diseases
Sleep Disorders, Circadian Rhythm
Dyssomnias
Sleep Disorders
Mental Disorders
Melatonin
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Anti-Inflammatory Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on September 30, 2014