Effects of Daytime Eszopiclone Administration in Shift Workers

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

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

Study Overview

• Status: Completed
• Conditions: Shift-Work Sleep Disorder
• Intervention / Treatment: Drug: eszopiclone; Drug: matching placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Massachusetts General Hospital; Sunovion

Publications and helpful links

General Publications

• Marino M, Li Y, Pencina MJ, D'Agostino RB Sr, Berkman LF, Buxton OM. Quantifying cardiometabolic risk using modifiable non-self-reported risk factors. Am J Prev Med. 2014 Aug;47(2):131-40. doi: 10.1016/j.amepre.2014.03.006. Epub 2014 Jun 17.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: April 13, 2009
• First Submitted That Met QC Criteria: May 11, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Actual): August 30, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: MWT; eszopiclone; Shift-work; SWSD; shiftworkers
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Neurologic Manifestations; Occupational Diseases; Chronobiology Disorders; Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: ESRC-977; 2009-P-000019 (Other Identifier: Brigham and Women's Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: After publication of initial results, would require institutional data sharing agreement with Partners Inc (Brigham and Women's Hospital), and Dr. Buxton