Ramelteon for a Nap Prior to a Night Shift
Study Details
Study Description
Brief Summary
Night shift-workers are often advised to take a prophylactic nap prior to starting the shift in order to improve alertness and performance. However, individuals often report difficulty initiating and maintaining sleep at that time of the day secondary to the alerting influence of the near-24 hour circadian rhythm (biological clock). A sleep-promoting medication may improve the quality of an evening nap and subsequent alertness and performance during a night shift. We will use Ramelteon, a melatonin agonist that is FDA approved for insomnia, in order to test the following hypotheses:
-
ramelteon, compared with placebo, will significantly increase sleep efficiency during a 2-hour nap;
-
sleep inertia, as assessed by neurobehavioral tests and subjective and objective sleepiness assessments will not be significantly increased after ramelteon treatment compared with placebo treatment; and
-
neurobehavioral performance, subjective and objective sleepiness, and subjective mood during a simulated 8-hour night shift will be significantly improved when ramelteon is given prior to a prophylactic nap compared to a prophylactic nap with placebo.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 1 Ramelteon 8 mg will be given once prior to a 2-hour nap |
Drug: Ramelteon
Ramelteon 8 mg tablet by mouth x 1 dose
Other Names:
|
Placebo Comparator: 2 Placebo will be given once prior to a 2-hour nap |
Drug: placebo
placebo identical in appearance to active experimental drug x 1 dose
|
Outcome Measures
Primary Outcome Measures
- Sleep Efficiency [2 hours]
total sleep time/time in bed * 100% (higher values indicate better outcome)
Other Outcome Measures
- Post-nap Assessment - Visual Analog Scale [71 minutes]
numerical scale of increasing alertness from 0-100 (higher values are better outcome)
- Post Nap Assessment - Karolinska Sleepiness Scale [71 minutes]
numerical scale of increasing sleepiness from 1-9 (higher values indicate worse outcome)
- Post Nap Assessment - Digit Symbol Substitution Test (Correct Answers) [71 minutes]
A cognitive throughput task consisting of matching symbols to numerical keys; higher numbers indicate a better score
- Post Nap Assessment - Karolinska Drowsiness Test [71 minutes]
EEG spectral analysis of 5.5-9.0 Hz frequency activity (theta low-frequency alpha), with higher activity indicating increased drowsiness and worse outcome
- Psychomotor Vigilance Task - Median Reaction Time [8 hours]
Visual-motor reaction time in which participants hit a button on a response box as fast as possible in response to a visual target (lower values indicate better outcome)
- Psychomotor Vigilance Task - Number of Lapses [8 hours]
Number of trials per test battery with a reaction time >0.5 seconds (higher values indicate worse outcome)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged between 18-35 years;
-
Non-smoking for at least 6 months;
-
Healthy (no medical, psychiatric or sleep disorders);
-
No clinically significant deviations from normal in medical history, vital signs, physical examination, blood chemistry and hematology, and ECG;
-
Women of childbearing potential must agree to use an acceptable method of birth control, and must have a negative serum pregnancy test;
-
Body mass index of > 18 or < 30 kg/m∧2;
-
No drugs or medication likely to affect sleep or alertness, as determined by the investigators;
-
Habitual caffeine consumption < 300 mg per day on average;
-
Habitual alcohol consumption < 10 alcoholic units per week on average.
Exclusion Criteria:
-
History of alcohol or substance abuse;
-
Positive result on drugs of abuse screening;
-
Current or past history of sleep disorders, including but not limited to obstructive sleep apnea, or any significant sleep complaint;
-
Psychiatric disorder, including a history of depression or dysthymia (characterized by depressed mood on the majority of days for at least two years);
-
Recent acute or chronic medical disorder, including but not limited to hepatic impairment and severe chronic obstructive pulmonary disease;
-
History of intolerance or hypersensitivity to melatonin or melatonin agonists;
-
Pregnancy or lactation;
-
Shift work;
-
Transmeridian travel (2 or more time zones) in past 2 months;
-
Any other scientific or medical reason, as determined by the PI, such as non-compliance with protocol or intolerance to inpatient study conditions.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Brigham and Women's Hospital
- Takeda
Investigators
- Principal Investigator: Shantha Rajaratnam, PhD, Brigham and Women's Hosptial
- Principal Investigator: Elizabeth B Klerman, MD,PhD, Brigham and Women's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Takeda - 103113
Study Results
Participant Flow
Recruitment Details | Healthy volunteers were recruited |
---|---|
Pre-assignment Detail | Participants received 1 dose of ramelteon or placebo during the first inpatient visit and then returned approximately four weeks later for the other condition, counterbalanced for order |
Arm/Group Title | Ramelteon in First Crossover Period | Placebo in First Crossover Period |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Period Title: Overall Study | ||
STARTED | 6 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Ramelteon in First Crossover Period | Placebo in First Crossover Period | Total |
---|---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap | Total of all reporting groups |
Overall Participants | 6 | 5 | 11 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
6
100%
|
5
100%
|
11
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
22.7
(4.1)
|
26.8
(3.2)
|
24.5
(4.1)
|
Sex: Female, Male (Count of Participants) | |||
Female |
2
33.3%
|
4
80%
|
6
54.5%
|
Male |
4
66.7%
|
1
20%
|
5
45.5%
|
Region of Enrollment (participants) [Number] | |||
United States |
6
100%
|
5
100%
|
11
100%
|
Outcome Measures
Title | Sleep Efficiency |
---|---|
Description | total sleep time/time in bed * 100% (higher values indicate better outcome) |
Time Frame | 2 hours |
Outcome Measure Data
Analysis Population Description |
---|
All participants that completed both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [percent] |
89.1
(9.8)
|
83.3
(14.3)
|
Title | Post-nap Assessment - Visual Analog Scale |
---|---|
Description | numerical scale of increasing alertness from 0-100 (higher values are better outcome) |
Time Frame | 71 minutes |
Outcome Measure Data
Analysis Population Description |
---|
All participants that completed both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [units on a scale] |
61.1
(18.6)
|
67.1
(22.8)
|
Title | Post Nap Assessment - Karolinska Sleepiness Scale |
---|---|
Description | numerical scale of increasing sleepiness from 1-9 (higher values indicate worse outcome) |
Time Frame | 71 minutes |
Outcome Measure Data
Analysis Population Description |
---|
All participants that completed both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [units on a scale] |
5.4
(1.6)
|
4.8
(1.8)
|
Title | Post Nap Assessment - Digit Symbol Substitution Test (Correct Answers) |
---|---|
Description | A cognitive throughput task consisting of matching symbols to numerical keys; higher numbers indicate a better score |
Time Frame | 71 minutes |
Outcome Measure Data
Analysis Population Description |
---|
All participants that completed both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [correct answers] |
50.4
(9.3)
|
53.3
(9.3)
|
Title | Post Nap Assessment - Karolinska Drowsiness Test |
---|---|
Description | EEG spectral analysis of 5.5-9.0 Hz frequency activity (theta low-frequency alpha), with higher activity indicating increased drowsiness and worse outcome |
Time Frame | 71 minutes |
Outcome Measure Data
Analysis Population Description |
---|
All participants completing both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [microvolts^2/Hz] |
4.9
(4.5)
|
4.0
(5.6)
|
Title | Psychomotor Vigilance Task - Median Reaction Time |
---|---|
Description | Visual-motor reaction time in which participants hit a button on a response box as fast as possible in response to a visual target (lower values indicate better outcome) |
Time Frame | 8 hours |
Outcome Measure Data
Analysis Population Description |
---|
All participants completing both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [seconds] |
0.662
(0.16)
|
0.362
(0.25)
|
Title | Psychomotor Vigilance Task - Number of Lapses |
---|---|
Description | Number of trials per test battery with a reaction time >0.5 seconds (higher values indicate worse outcome) |
Time Frame | 8 hours |
Outcome Measure Data
Analysis Population Description |
---|
All participants completing both crossover periods |
Arm/Group Title | Ramelteon | Placebo |
---|---|---|
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [lapses] |
15.5
(16.3)
|
13.2
(16.0)
|
Adverse Events
Time Frame | During each 28-hr inpatient study admission | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Ramelteon | Placebo | ||
Arm/Group Description | Ramelteon 8 mg will be given prior to a 2-hour nap | Placebo will be given prior to a 2-hour nap | ||
All Cause Mortality |
||||
Ramelteon | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Ramelteon | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/11 (0%) | 0/10 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Ramelteon | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/11 (0%) | 0/10 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Daniel Cohen |
---|---|
Organization | Sentara Neurology Specialists |
Phone | 757-388-6323 |
dacohen@sentara.com |
- Takeda - 103113