Ramelteon for a Nap Prior to a Night Shift

Sponsor
Brigham and Women's Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT00595075
Collaborator
Takeda (Industry)
11
2
11

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:

  1. ramelteon, compared with placebo, will significantly increase sleep efficiency during a 2-hour nap;

  2. 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

  3. 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

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Effects of Ramelteon on Sleep and Neurobehavioral Performance in a Simulated Night Shift Preceded by a Sleep Opportunity
Study Start Date :
Dec 1, 2007
Actual Primary Completion Date :
Nov 1, 2008
Actual Study Completion Date :
Nov 1, 2008

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:
  • Rozerem
  • 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

    1. Sleep Efficiency [2 hours]

      total sleep time/time in bed * 100% (higher values indicate better outcome)

    Other Outcome Measures

    1. Post-nap Assessment - Visual Analog Scale [71 minutes]

      numerical scale of increasing alertness from 0-100 (higher values are better outcome)

    2. Post Nap Assessment - Karolinska Sleepiness Scale [71 minutes]

      numerical scale of increasing sleepiness from 1-9 (higher values indicate worse outcome)

    3. 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

    4. 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

    5. 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)

    6. 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

    Ages Eligible for Study:
    18 Years to 35 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.
    Responsible Party:
    Elizabeth B. Klerman, Associate Professor, Associate Physician, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT00595075
    Other Study ID Numbers:
    • Takeda - 103113
    First Posted:
    Jan 16, 2008
    Last Update Posted:
    Oct 30, 2012
    Last Verified:
    Oct 1, 2012
    Keywords provided by Elizabeth B. Klerman, Associate Professor, Associate Physician, Brigham and Women's Hospital

    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

    1. Primary Outcome
    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)
    2. Other Pre-specified Outcome
    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)
    3. Other Pre-specified Outcome
    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)
    4. Other Pre-specified Outcome
    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)
    5. Other Pre-specified Outcome
    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)
    6. Other Pre-specified Outcome
    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)
    7. Other Pre-specified Outcome
    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

    Circadian phase was not measured.

    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
    Email dacohen@sentara.com
    Responsible Party:
    Elizabeth B. Klerman, Associate Professor, Associate Physician, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT00595075
    Other Study ID Numbers:
    • Takeda - 103113
    First Posted:
    Jan 16, 2008
    Last Update Posted:
    Oct 30, 2012
    Last Verified:
    Oct 1, 2012