Circadian DysregulationPhase 4NCT00492011
Efficacy of Ramelteon on Insomnia Symptoms Associated With Jet Lag in Healthy Adult Volunteers
A Phase 4 study testing Ramelteon in people with Circadian Dysregulation, run by Takeda at 4 sites in United States.
Trial summary
The purpose of this study to determine the degree to which ramelteon, once daily (QD), can reduce the insomnia symptoms associated with rapid, eastward travel across 5 time zones. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Circadian Dysregulation
- What is being tested?
- Ramelteon
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2007to Aug 2007
- Phase
- Phase 4
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Willing to travel from Hawaii to the East Coast and have a minimum stay of 6 days at the destination in a sleep laboratory during the entire study.
- Has lived in Hawaii for at least 12 months and has not been traveling outside of Hawaii for 4 consecutive days within 30 days prior to the Outpatient Screening Visit.
- History of sleep disturbance associated with jet lag symptoms, with at least two occurrences in the last three years, as defined in the International Classification of Sleep Disorders.
- Habitual bedtime should be determined by sleep history as between 9:00 PM and 12:00 AM as determined by sleep history prior to randomization.
- Have regular bedtime (within 1 hour) for 1 week prior to travel.
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- The subject has a subjective sleep latency of less than 30 minutes and a subjective total sleep time of 6.5 hours but less than 9 hours, as determined by sleep history.
- Mean subjective sleep latency of less than 30 minutes and a mean subjective total sleep time of greater than 6.5 hours but less than 9 hours in 3 of 5 nights after the outpatient screening visit, as determined by post-sleep questionnaire.
- Willingness and ability to comply with study procedures, including travel time, sleep, and waking-hour activities, light-exposure restriction, and food intake.
- Body mass index between 18 and 34, inclusive.
- Negative test result for selected substances of abuse (including alcohol) at Initial Screening, the In-Patient Actigraphy Screening Nights 1 and 2, and the Treatment Period.
- Negative test result for hepatitis B Surface antigen and hepatitis C virus antibody.
Who cannot join
- Known hypersensitivity to ramelteon or related compounds, including melatonin, and melatonin related compounds.
- History of primary sleep disorders as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised within the past 6 months.
- Current sleep disorder as assessed by presence of sleep apnea, period leg movement syndrome, insomnia, daytime napping of more than 20 minutes, chronic fatigue.
- Ever had a history of seizures, sleep apnea, restless leg syndrome, periodic limb movement syndrome, or chronic obstructive pulmonary disease.
- History of psychiatric disorder (including schizophrenia, bipolar disorder, mental retardation, or cognitive disorder, anxiety, or depression) within the past 12 months.
- Current, clinically significant neurological (including cognitive), hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematological, or metabolic disease, as determined by the investigator.
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- History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised, or regularly consumes more than 14 alcoholic drinks per week.
- History of drug abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised.
- Positive urine drug screen or a positive urine drug screen or alcohol breathalyzer test.
- Sleep schedule changes required by employment (eg, shift worker) within 3 months prior to the administration of single blind study medication.
- Positive hepatitis panel including anti- hepatitis A virus (only IgM is exclusionary), hepatitis B surface antigen, or anti- hepatitis C virus.
- Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
- Any additional condition(s) that in the Investigator's opinion would:
- affect sleep/wake function
- prohibit the subject from completing the study
- cause a situation such that it would not be in the best interest of the subject to participate in the study.
- Participated in a weight loss program or has substantially altered their exercise routine within 30 days prior to the administration of study medication.
- Smokes greater than 3 cigarettes per day or uses tobacco products during nightly awakenings.
- Has flown across greater than 3 time zones within 28 days prior to or during screening.
- Reports high caffeine consumption (greater than 600 mg daily).
- Participated in any other investigational study and/or taken any investigational drug within 30 days or 5 half-lives of the investigational drug prior to the first dose of double blind study medication, whichever is longer.
- Used any central nervous system medication within 1 week (or 5 half lives of the drug, whichever is longer) prior to the administration of study medication. These medications must not have been used to treat psychiatric disorders.
- Used prescription or over-the-counter (OTC) hypnotic medication (including melatonin) within 3 months of the screening visits.
- Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Anxiolytics
- Sedatives
- Antidepressants
- CNS active drugs (including herbal)
- Anticonvulsants
- Narcotic analgesics
- Sedating H1 antihistamines
- St. John's Wort
- Systemic steroids
- Kava-kava
- Respiratory stimulants
- Ginkgo-biloba
- Decongestants
- Over-the-counter and prescription stimulants
- Antipsychotics
- Over-the-counter and prescription diet aids
- Muscle Relaxants Drugs affecting sleep/wake function
- Melatonin
- Modafinil
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Study site
Honolulu, Hawaii
Study site
Miami, Florida
Study site
New York, New York
Study site
Pembroke Pines, Florida
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Ability of Ramelteon 1 mg, 4 mg, and 8 mg to Alleviate the Insomnia Symptoms Associated With Eastward Bound Jet Lag Across 5 Time Zones in Healthy Adult Volunteers
The purpose of this study to determine the degree to which ramelteon, once daily (QD), can reduce the insomnia symptoms associated with rapid, eastward travel across 5 time zones.
Read the detailed description
Circadian dysrhythmia, or jet lag, is defined as multiple biologic and psychologic stresses created by rapid travel across multiple time zones. As more people are transported by jet aircraft, the issue of jet lag becomes more important. What was an inconvenience during travel for leisure is now a physiologic consequence for the travelers and crew.
Jet lag is composed of a variety of unpleasant symptoms that vary with the number of time zones crossed, the individual, and even the direction flown (east versus west). The most typical symptoms include daytime sleepiness, fatigue, impaired alertness, and trouble initiating and maintaining sleep. Other symptoms of circadian dysrhythmia are insomnia, gastrointestinal complaints, apathy, weakness, irritability, malaise, and loss of appetite. Travel across time zones also has been associated with diabetic ketoacidosis, depression, and impaired cognitive performance in individuals at risk. Decreased sport performance has been noted in several studies.
In addition to environmental and social cues, physical factors, such as age, hydration status, and illness, could adversely affect the ability to entrain (adjust) quickly. The stressors of flight, noise, vibration, decreased humidity, barometric pressure changes, and decreased partial pressure of oxygen all contribute to crew and travelers health at the destination.
Being out of synchronicity with the environment causes jet lag symptoms. Travel through time zones places the body in a situation when it must sleep when not tired and awaken when the internal cues are initiating sleep. The brain's internal clock is the suprachiasmatic nucleus within the hypothalamus the body is in a constant state of circadian adjustment to remain entrained to a given time zone. In addition to the subjective feeling of well being are measurable changes associated with daily patterns. For example, core body temperature changes throughout the day and decreases before falling asleep. Melatonin levels increase in the evening and night and recede during the day.
Ramelteon is a melatonin receptor 1 and melatonin receptor 2 agonist currently marketed in the US for the treatment of insomnia characterized by difficulty with sleep onset. Study participation is anticipated to be about 2 weeks.
- Conditions
- Circadian Dysregulation
- Being tested
- Ramelteon, Placebo
- Keywords
- Circadian Rhythm Disorders, Biological Clock Disturbances, Jet Lag Syndrome, Time Zone Change Syndrome, Drug Therapy
- Medical subject headings
- Chronobiology Disorders, Jet Lag Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamelteonDrug
Also called TAK-375, Rozerem™
Ramelteon 1 mg, tablets, orally, once nightly for 4 nights.
RamelteonDrug
Also called TAK-375, Rozerem™
Ramelteon 4 mg, tablets, orally, once nightly for 4 nights.
RamelteonDrug
Also called TAK-375, Rozerem™
Ramelteon 8 mg, tablets, orally, once nightly for 4 nights.
PlaceboDrug
Ramelteon placebo-matching tablets, orally, once nightly for 4 nights.
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon 1 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Ramelteon 4 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Ramelteon 8 mg QD | Experimental | Not described Receives: Drug: Ramelteon |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Latency to Persistent Sleep measured by polysomnography.
Measured: Nights 2, 3, and 4
Secondary outcomes (11)
Dim light melatonin offset time in a subset of subjects defined as the time of the morning when the melatonin drops to below 3 pg/mL with a downward slope.
Measured: Nights 2, 3, and 4
Total sleep time in minutes by polysomnography.
Measured: Nights 2, 3, and 4
Number of awakenings after persistent sleep by polysomnography.
Measured: Nights 2, 3, and 4
Wake time after persistent sleep onset by polysomnography.
Measured: Nights 2, 3, and 4
Sleep efficiency by polysomnography.
Measured: Nights 2, 3, and 4
Karolinska Sleepiness Scale
Measured: Days 1, 2, 3, 4 and 5
Pittsburgh Sleep Quality Index
Measured: Day 6
Daytime Function measured by Daytime Function Questionnaire (DTFQ) and Psychomotor Vigilance test (PVT)
Measured: Day 3
Digit Symbol Substitution Test
Measured: Days 1, 2, 3, 4 and 5
Memory Recall Test
Measured: Days 1, 2, 3, 4 and 5
Visual Analogue Scale for Mood and Feelings, level of alertness and ability to concentrate
Measured: Days 1, 2, 3, 4 and 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2007 (estimated)
- Study startFeb 2007
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Circadian DysregulationStudies of the same condition, open and under way.
- More trials run by TakedaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00492011
- Sponsor's protocol ID
- 01-04-TL-375-045
- Other IDs
- U1111-1115-1566
- Status last verified
- Feb 2012
- First submitted
- 25 Jun 2007
- Last updated
- 28 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Zee PC, Wang-Weigand S, Wright KP Jr, Peng X, Roth T. Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel. Sleep Med. 2010 Jun;11(6):525-33. doi: 10.1016/j.sleep.2010.03.010. Epub 2010 May 18.
PubMed 20483660
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Ability of Ramelteon 1 mg, 4 mg, and 8 mg to Alleviate the Insomnia Symptoms Associated With Eastward Bound Jet Lag Across 5 Time Zones in Healthy Adult Volunteers
- ClinicalTrials.gov ID
- NCT00492011
- Acronym / sponsor ID
- 01-04-TL-375-045
- Conditions
- Circadian Dysregulation
- Keywords
- Circadian Rhythm Disorders, Biological Clock Disturbances, Jet Lag Syndrome, Time Zone Change Syndrome, Drug Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 27 Jun 2007 (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.
The purpose of this study to determine the degree to which ramelteon, once daily (QD), can reduce the insomnia symptoms associated with rapid, eastward travel across 5 time zones.
Detailed description
Circadian dysrhythmia, or jet lag, is defined as multiple biologic and psychologic stresses created by rapid travel across multiple time zones. As more people are transported by jet aircraft, the issue of jet lag becomes more important. What was an inconvenience during travel for leisure is now a physiologic consequence for the travelers and crew.
Jet lag is composed of a variety of unpleasant symptoms that vary with the number of time zones crossed, the individual, and even the direction flown (east versus west). The most typical symptoms include daytime sleepiness, fatigue, impaired alertness, and trouble initiating and maintaining sleep. Other symptoms of circadian dysrhythmia are insomnia, gastrointestinal complaints, apathy, weakness, irritability, malaise, and loss of appetite. Travel across time zones also has been associated with diabetic ketoacidosis, depression, and impaired cognitive performance in individuals at risk. Decreased sport performance has been noted in several studies.
In addition to environmental and social cues, physical factors, such as age, hydration status, and illness, could adversely affect the ability to entrain (adjust) quickly. The stressors of flight, noise, vibration, decreased humidity, barometric pressure changes, and decreased partial pressure of oxygen all contribute to crew and travelers health at the destination.
Being out of synchronicity with the environment causes jet lag symptoms. Travel through time zones places the body in a situation when it must sleep when not tired and awaken when the internal cues are initiating sleep. The brain's internal clock is the suprachiasmatic nucleus within the hypothalamus the body is in a constant state of circadian adjustment to remain entrained to a given time zone. In addition to the subjective feeling of well being are measurable changes associated with daily patterns. For example, core body temperature changes throughout the day and decreases before falling asleep. Melatonin levels increase in the evening and night and recede during the day.
Ramelteon is a melatonin receptor 1 and melatonin receptor 2 agonist currently marketed in the US for the treatment of insomnia characterized by difficulty with sleep onset. Study participation is anticipated to be about 2 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ramelteon 1 mg QD | Experimental | Drug: Ramelteon |
| Ramelteon 4 mg QD | Experimental | Drug: Ramelteon |
| Ramelteon 8 mg QD | Experimental | Drug: Ramelteon |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Willing to travel from Hawaii to the East Coast and have a minimum stay of 6 days at the destination in a sleep laboratory during the entire study.
- Has lived in Hawaii for at least 12 months and has not been traveling outside of Hawaii for 4 consecutive days within 30 days prior to the Outpatient Screening Visit.
- History of sleep disturbance associated with jet lag symptoms, with at least two occurrences in the last three years, as defined in the International Classification of Sleep Disorders.
- Habitual bedtime should be determined by sleep history as between 9:00 PM and 12:00 AM as determined by sleep history prior to randomization.
Key exclusion criteria (43 listed)
- Known hypersensitivity to ramelteon or related compounds, including melatonin, and melatonin related compounds.
- History of primary sleep disorders as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised within the past 6 months.
- Current sleep disorder as assessed by presence of sleep apnea, period leg movement syndrome, insomnia, daytime napping of more than 20 minutes, chronic fatigue.
- Ever had a history of seizures, sleep apnea, restless leg syndrome, periodic limb movement syndrome, or chronic obstructive pulmonary disease.
- History of psychiatric disorder (including schizophrenia, bipolar disorder, mental retardation, or cognitive disorder, anxiety, or depression) within the past 12 months.
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 |
|---|---|---|
| RamelteonAlso: TAK-375, Rozerem™Ramelteon 1 mg, tablets, orally, once nightly for 4 nights. | Drug | Ramelteon 1 mg QD |
| RamelteonAlso: TAK-375, Rozerem™Ramelteon 4 mg, tablets, orally, once nightly for 4 nights. | Drug | Ramelteon 4 mg QD |
| RamelteonAlso: TAK-375, Rozerem™Ramelteon 8 mg, tablets, orally, once nightly for 4 nights. | Drug | Ramelteon 8 mg QD |
| PlaceboRamelteon placebo-matching tablets, orally, once nightly for 4 nights. | Drug | Placebo |
Primary outcome
Average Latency to Persistent Sleep measured by polysomnography.
Time frame: Nights 2, 3, and 4
11 secondary outcomes
Dim light melatonin offset time in a subset of subjects defined as the time of the morning when the melatonin drops to below 3 pg/mL with a downward slope.
Time frame: Nights 2, 3, and 4
Total sleep time in minutes by polysomnography.
Time frame: Nights 2, 3, and 4
Number of awakenings after persistent sleep by polysomnography.
Time frame: Nights 2, 3, and 4
Wake time after persistent sleep onset by polysomnography.
Time frame: Nights 2, 3, and 4
Sleep efficiency by polysomnography.
Time frame: Nights 2, 3, and 4
Karolinska Sleepiness Scale
Time frame: Days 1, 2, 3, 4 and 5
Pittsburgh Sleep Quality Index
Time frame: Day 6
Daytime Function measured by Daytime Function Questionnaire (DTFQ) and Psychomotor Vigilance test (PVT)
Time frame: Day 3
Digit Symbol Substitution Test
Time frame: Days 1, 2, 3, 4 and 5
Memory Recall Test
Time frame: Days 1, 2, 3, 4 and 5
Visual Analogue Scale for Mood and Feelings, level of alertness and ability to concentrate
Time frame: Days 1, 2, 3, 4 and 5
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 28 Feb 2012.
- Results publication: PubMed 20483660Zee PC, Wang-Weigand S, Wright KP Jr, Peng X, Roth T. Effects of ramelteon on insomnia symptoms induced by rapid, eastward travel. Sleep Med. 2010 Jun;11(6):525-33. doi: 10.1016/j.sleep.2010.03.010. Epub 2010 May 18.
- Rozerem Package InsertLink 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.
Medical Director Clinical Science study director
Takeda
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramelteon in people with Circadian Dysregulation, run by Takeda at 4 sites 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 12 inclusion and 43 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 28 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Average Latency to Persistent Sleep measured by polysomnography. (time frame: Nights 2, 3, and 4). 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 NCT00492011, which also lists 1 linked publication.
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 28 Feb 2012.