Jet LagPhase 2NCT00097474
Effects of Hydrocortisone, Melatonin, and Placebo on Jet Lag
A Phase 2 study testing Hydrocortisone and Melatonin in people with Jet Lag, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Jet Lag
- What is being tested?
- Hydrocortisone and Melatonin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2004to 14 Nov 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet Lag
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:
Read more
- 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.
Read the 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.
- Conditions
- Jet Lag
- Being tested
- Hydrocortisone, Melatonin, Placebo
- Keywords
- Cortisol, Jet Lag, Healthy Volunteer, HV
- Medical subject headings
- Jet Lag Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Hydrocortisone will be given alone or in combination with Melatonin to see if symptoms of jet lag are alleviated
MelatoninDrug
Melatonin will be given alone or in combination with Hydrocortisone to see if symptoms of jet lag are alleviated
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Combination | Experimental | Both HC 30 and ML 5 will be administered Receives: Drug: Hydrocortisone; Drug: Melatonin |
| Hydrocortisone | Experimental | 30mg Hydrocortisone will be administered Receives: Drug: Hydrocortisone |
| Melatonin | Experimental | 5 mg Melatonin will be administered Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
improvement in jet lag symptoms
Patients will report jet lag symptoms via questionnaire
Measured: 10 days
Secondary outcomes (1)
salivary cortisol level
salivary cortisol at bedtime will be measured
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2004 (estimated)
- Study start21 Dec 2004
- Primary completion6 Jan 2006
- Study completion14 Nov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Jet LagStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lynnette K Nieman, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00097474
- Sponsor's protocol ID
- 050037
- Other IDs
- 05-CH-0037
- Status last verified
- 14 Oct 2026
- First submitted
- 23 Nov 2004
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 3085768Buxton 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.
PubMed 11083601Cho 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.
PubMed 10704520
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Hydrocortisone, Melatonin, and Placebo on Symptoms of Jet Lag
- ClinicalTrials.gov ID
- NCT00097474
- Acronym / sponsor ID
- 050037
- Conditions
- Jet Lag
- Keywords
- Cortisol, Jet Lag, Healthy Volunteer, HV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 21 Dec 2004 (actual)
- Primary completion
- 6 Jan 2006 (actual)
- Study completion
- 14 Nov 2007 (actual)
- First posted
- 24 Nov 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Combination | Experimental | Drug: Hydrocortisone, Drug: MelatoninBoth HC 30 and ML 5 will be administered |
| Hydrocortisone | Experimental | Drug: Hydrocortisone30mg Hydrocortisone will be administered |
| Melatonin | Experimental | Drug: Melatonin5 mg Melatonin will be administered |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydrocortisoneHydrocortisone will be given alone or in combination with Melatonin to see if symptoms of jet lag are alleviated | Drug | Combination, Hydrocortisone |
| MelatoninMelatonin will be given alone or in combination with Hydrocortisone to see if symptoms of jet lag are alleviated | Drug | Combination, Melatonin |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
improvement in jet lag symptoms
Time frame: 10 days
Patients will report jet lag symptoms via questionnaire
1 secondary outcome
salivary cortisol level
Time frame: 10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Background: PubMed 3085768Arendt 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.
- Background: PubMed 11083601Buxton 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.
- Background: PubMed 10704520Cho 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynnette K Nieman, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydrocortisone and Melatonin in people with Jet Lag, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
improvement in jet lag symptoms (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00097474, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.