Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag

NCT00097474 | Completed Phase 2 FDA Drug

• 2 other identifiers: 05003705-CH-0037
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Jet Lag

Keywords

Cortisol; Jet Lag; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• improvement in jet lag symptoms

  Patients will report jet lag symptoms via questionnaire

  10 days

Secondary Outcomes (1)

• salivary cortisol level

  10 days

Study Arms (4)

Combination

EXPERIMENTAL

Both HC 30 and ML 5 will be administered

Drug: Hydrocortisone; Drug: Melatonin

Hydrocortisone

EXPERIMENTAL

30mg Hydrocortisone will be administered

Drug: Hydrocortisone

Melatonin

EXPERIMENTAL

5 mg Melatonin will be administered

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Hydrocortisone DRUG

Hydrocortisone will be given alone or in combination with Melatonin to see if symptoms of jet lag are alleviated

Combination; Hydrocortisone

Melatonin DRUG

Melatonin will be given alone or in combination with Hydrocortisone to see if symptoms of jet lag are alleviated

Combination; Melatonin

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18, but less than or equal to 65, male or female.
• Normal physical exam and laboratory results.
• Negative urinary pregnancy test 1 week prior to travel (pre-menopausal women).
• Planned eastward flight crossing 6-8 time zones between 30n and 50n latitudes.
• A minimum stay of 7 - 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.

You may not qualify if:

• 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.
• Fasting blood glucose greater than 110 mg/dL or known diabetes.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Arendt J, Aldhous M, Marks V. Alleviation of jet lag by melatonin: preliminary results of controlled double blind trial. Br Med J (Clin Res Ed). 1986 May 3;292(6529):1170. doi: 10.1136/bmj.292.6529.1170. No abstract available.

  PMID: 3085768 BACKGROUND

• Buxton OM, Copinschi G, Van Onderbergen A, Karrison TG, Van Cauter E. A benzodiazepine hypnotic facilitates adaptation of circadian rhythms and sleep-wake homeostasis to an eight hour delay shift simulating westward jet lag. Sleep. 2000 Nov 1;23(7):915-27.

  PMID: 11083601 BACKGROUND

• Cho K, Ennaceur A, Cole JC, Suh CK. Chronic jet lag produces cognitive deficits. J Neurosci. 2000 Mar 15;20(6):RC66. doi: 10.1523/JNEUROSCI.20-06-j0005.2000.

  PMID: 10704520 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Jet Lag Syndrome

Interventions

Hydrocortisone; Melatonin

Condition Hierarchy (Ancestors)

Chronobiology Disorders; Nervous System Diseases; Sleep Disorders, Circadian Rhythm; Dyssomnias; Sleep Wake Disorders; Travel-Related Illness; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lynnette K Nieman, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2004
• First Posted: November 24, 2004
• Study Start: December 21, 2004
• Primary Completion: January 6, 2006
• Study Completion: November 14, 2007
• Last Updated: June 8, 2026

Record last verified: 2026-04-16

Locations

US (1)