Ramelteon for a Nap Prior to a Night Shift

• ClinicalTrials.gov Identifier: NCT00595075
• Recruitment Status: Completed
• First Posted: January 16, 2008
• Results First Posted: October 12, 2012
• Last Update Posted: October 30, 2012
• Sponsor: Brigham and Women's Hospital
• Collaborator: Takeda
• Information provided by (Responsible Party): Elizabeth B. Klerman, Brigham and Women's Hospital

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
Healthy	Drug: Ramelteon; Drug: placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: December 2007
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 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 Name: 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 [ Time Frame: 2 hours ]
   total sleep time/time in bed * 100% (higher values indicate better outcome)

Other Outcome Measures:

1. Post-nap Assessment - Visual Analog Scale [ Time Frame: 71 minutes ]
   numerical scale of increasing alertness from 0-100 (higher values are better outcome)
2. Post Nap Assessment - Karolinska Sleepiness Scale [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 8 hours ]
   Number of trials per test battery with a reaction time >0.5 seconds (higher values indicate worse outcome)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

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

More Information

Publications of Results:

Cohen DA, Wang W, Klerman EB, Rajaratnam SM. Ramelteon prior to a short evening nap impairs neurobehavioral performance for up to 12 hours after awakening. J Clin Sleep Med. 2010 Dec 15;6(6):565-71.

• 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: January 16, 2008
• Results First Posted: October 12, 2012
• Last Update Posted: October 30, 2012
• Last Verified: October 2012

Keywords provided by Elizabeth B. Klerman, Brigham and Women's Hospital:

sleep; performance; night shift; Ramelteon; Healthy Individuals