Effects of Daytime Eszopiclone Administration in Shift Workers

Study Overview
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Brief Summary
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The purpose of this study is to test the effects of eszopiclone on daytime sleep and overnight wakefulness in shift workers.

Detailed Description
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The current study seeks to extend the currently available treatments for SWSD by addressing the putative root cause of the problem-the inability of night-shift workers with or without SWSD- to obtain adequate daytime sleep in the face of the circadian drive for alertness that increases across the biological day. Even healthy, young subjects who are sleep-deprived overnight exhibit daytime sleep marked by frequent awakenings and low sleep efficiency, less slow-wave sleep, and altered sleep architecture, e.g. earlier predominance of REM sleep. Many night-workers routinely report 3-6 hours of habitual sleep duration for daytime sleep. Pharmacological interventions to decrease awakenings and improve total sleep time during daytime sleep could improve subsequent alertness during a night shift. Improving the wakefulness of night-shift workers over the nighttime could result in substantial benefits for the individual workers, improve workplace productivity and safety, and improve public health.

Official Title
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Effects of Daytime Eszopiclone Administration in Shift Workers on Overnight Wakefulness During a Subsequent Simulated Nightshift

Conditions
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Shift-Work Sleep Disorder

Intervention / Treatment
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* Drug: eszopiclone
* Drug: matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-50 (men or women) Current shift worker (for at least 3 months, at least 5 overnights/month and 3 consecutive) A willingness and ability to comply with study procedures If of child-bearing potential, using a medically-accepted method of birth control, including abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method, or intrauterine device [IUD]). Exclusion Criteria: Current diagnosis of DSM-IV Axis I disorder (other than insomnia) Regular treatment (>1time/wk) with CNS-active medication within 1 month of first inpatient visit Uncontrolled medical illness that would interfere with participation in the study BMI>32 or < 19.8 kg/m2 Current symptoms or diagnosis of any moderate to severe sleep disorder other than SWSD Periodic Leg Movement of Sleep Index (PLMSi)>20/hr of sleep or Respiratory Desaturation Index (RDI)>15 on polysomnography (PSG) Current alcohol or drug dependence/abuse Menopausal or peri-menopausal symptoms that disrupt sleep Pregnant, lactating, or planning to become pregnant Current smoking of more than 10 cigarettes per day Current use of over the counter sleep aids such as Benadryl or melatonin

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: eszopiclone<br>Treatment with eszopiclone | Drug: eszopiclone<br>* 3mg eszopiclone prior to daytime sleep for 3 days (at home) and 1 day (in lab)<br>* Other names: Lunesta;|
| Placebo Comparator: matching placebo<br>Treatment with matching placebo | Drug: eszopiclone<br>* 3mg eszopiclone prior to daytime sleep for 3 days (at home) and 1 day (in lab)<br>* Other names: Lunesta;Drug: matching placebo<br>* matching placebo prior to daytime sleep for 3 days (at home) and 1 day (in lab)<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nighttime Wakefulness Assessed by Mean Sleep Latency Across 4 Maintenance of Wakefulness Tests | Participants underwent four Maintenance of Wakefulness Tests (MWT) at 2-hour intervals during the simulated night shift starting 5 hours after wake time. MWT range from 0 to 40 minutes, where shorter times to fall asleep represent greater sleepiness (worse). MWT tests are averaged, for a mean in minutes. | On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG-recorded Sleep Efficiency | Polysomnographic recordings of daytime sleep were made at sleep screen (8.5hr) and during daytime sleep episodes of 8.5 hours of duration during treatment visits. Sleep efficiency is calculated based on the time the participant spent in bed and the actual time the participant slept. | On each treatment, during an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts | 
| Subjective Sleepiness and Performance | The Karolinska Sleepiness Scale (KSS), a nine point Visual Analog Scale of alertness/sleepiness, was used to assess subjective sleepiness. The KSS is a scale from 1 to 9, from minimum to maximum sleepiness. | On each treatment, after an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts | 
| Objective Vigilance Task Performance | A computer-based Flanker Task elicits responses to an incongruent pairing of stimuli measured as reaction time, in milliseconds. The Flanker task tests response inhibition, or the participants suppression of an unwanted response. A target stimulus (symbol) is flanked by non-target stimuli (symbols) that are the same as the target stimulus, opposite of the target stimulus, or neutral with respect to the target stimulus. The task is intended to assess the ability to maintain selective attention in the presence of distractors. | On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts | 
| Sleep-dependent Memory Consolidation | A computer-based Word-pair tasks is the number of words recalled after sleep from a list of words shown prior to going to sleep. | On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shift-work, SWSD, eszopiclone, MWT, shiftworkers