Ramelteon for a Nap Prior to a Night Shift

Effects of Ramelteon on Sleep and Neurobehavioral Performance in a Simulated Night Shift Preceded by a Sleep Opportunity

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ramelteon; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Efficiency	total sleep time/time in bed * 100% (higher values indicate better outcome)	2 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-nap Assessment - Visual Analog Scale	numerical scale of increasing alertness from 0-100 (higher values are better outcome)	71 minutes
Post Nap Assessment - Karolinska Sleepiness Scale	numerical scale of increasing sleepiness from 1-9 (higher values indicate worse outcome)	71 minutes
Post Nap Assessment - Digit Symbol Substitution Test (Correct Answers)	A cognitive throughput task consisting of matching symbols to numerical keys; higher numbers indicate a better score	71 minutes
Post Nap Assessment - Karolinska Drowsiness Test	EEG spectral analysis of 5.5-9.0 Hz frequency activity (theta low-frequency alpha), with higher activity indicating increased drowsiness and worse outcome	71 minutes
Psychomotor Vigilance Task - Median Reaction Time	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)	8 hours
Psychomotor Vigilance Task - Number of Lapses	Number of trials per test battery with a reaction time >0.5 seconds (higher values indicate worse outcome)	8 hours

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Takeda
• Investigators: Principal Investigator: Shantha Rajaratnam, PhD, Brigham and Women's Hosptial; Principal Investigator: Elizabeth B Klerman, MD,PhD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: January 7, 2008
• First Submitted That Met QC Criteria: January 15, 2008
• First Posted (ESTIMATE): January 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 30, 2012
• Last Update Submitted That Met QC Criteria: October 24, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: sleep; performance; Ramelteon; night shift; Healthy Individuals
• Other Study ID Numbers: Takeda - 103113