Effects of Daytime Eszopiclone Administration in Shift Workers

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00900159
• Collaborator: Sunovion (Industry), Massachusetts General Hospital (Other)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 9.1
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Shift-Work Sleep Disorder	Drug: eszopiclone; Drug: matching placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Daytime Eszopiclone Administration in Shift Workers on Overnight Wakefulness During a Subsequent Simulated Nightshift
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Nighttime Wakefulness Assessed by Mean Sleep Latency Across 4 Maintenance of Wakefulness Tests [On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts]

   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.

Secondary Outcome Measures

1. EEG-recorded Sleep Efficiency [On each treatment, during an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts]

   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.

2. Subjective Sleepiness and Performance [On each treatment, after an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts]

   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.

3. Objective Vigilance Task Performance [On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts]

   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.

4. Sleep-dependent Memory Consolidation [On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• Sunovion
• Massachusetts General Hospital

Investigators

• Principal Investigator: Orfeu M Buxton, Ph.D., Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Orfeu M. Buxton, Dr. Orfeu Buxton, Ph.D., Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00900159
• Other Study ID Numbers: ESRC-977; 2009-P-000019
• First Posted: May 12, 2009
• Last Update Posted: Aug 30, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Orfeu M. Buxton, Dr. Orfeu Buxton, Ph.D., Brigham and Women's Hospital: Shift-work; SWSD; eszopiclone; MWT; shiftworkers
• Additional relevant MeSH terms: Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm; Eszopiclone

Study Results

Participant Flow

Recruitment Details	The recruitment period was from April 2009 to December 2009. All recruitment happened at Brigham and Women's Hospital in Boston, MA. Recruitment included using advertisements around the Boston area.

Arm/Group Title	Eszopiclone Then Placebo	Placebo Then Eszopiclone
Arm/Group Description	Study participants on eszopiclone and then placebo	Study participants on placebo and then eszopiclone
Period Title: First Intervention
STARTED	11	13
COMPLETED	11	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	11	13
COMPLETED	11	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	11	13
COMPLETED	10	13
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Eszopiclone Then Placebo	Placebo Then Eszopiclone	Total
Arm/Group Description	Study participants on eszopiclone and then placebo	Study participants on placebo and then eszopiclone	Total of all reporting groups
Overall Participants	11	13	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	13 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	4 36.4%	8 61.5%	12 50%
Male	7 63.6%	5 38.5%	12 50%
Region of Enrollment (participants) [Number]
United States	11 100%	13 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Nighttime Wakefulness Assessed by Mean Sleep Latency Across 4 Maintenance of Wakefulness Tests
Description	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.
Time Frame	On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Medication for insomnia symptoms	Non-medicated pills
Measure Participants	23	23
Mean (95% Confidence Interval) [minutes]	11.0	14.75

2. Secondary Outcome

Title	EEG-recorded Sleep Efficiency
Description	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.
Time Frame	On each treatment, during an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Medication for insomnia symptoms	Non-medicated pills
Measure Participants	23	23
Mean (Standard Deviation) [percentage of time sleeping]	92.3 (5.1)	88.9 (9.6)

3. Secondary Outcome

Title	Subjective Sleepiness and Performance
Description	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.
Time Frame	On each treatment, after an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Medication for insomnia symptoms	Non-medicated pills
Measure Participants	23	23
Mean (Standard Error) [units on a scale]	5.0 (2.1)	5.3 (2.3)

4. Secondary Outcome

Title	Objective Vigilance Task Performance
Description	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.
Time Frame	On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Medication for insomnia symptoms	Non-medicated pills
Measure Participants	23	23
Mean (Standard Deviation) [milliseconds]	631 (260.5)	617 (294.9)

5. Secondary Outcome

Title	Sleep-dependent Memory Consolidation
Description	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.
Time Frame	On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Medication for insomnia symptoms	Non-medicated pills
Measure Participants	23	23
Mean (Standard Deviation) [words]	20.4 (8.1)	21.4 (6.7)

Adverse Events

Adverse Event Reporting Description	Adverse events characterized as per clinicaltrials.gov standards. All event were "Other (Not Including Serious) Adverse Events: Adverse events that are not Serious Adverse Events. " Systematic methods included regular investigator assessment.
Arm/Group Title	Eszopiclone		Placebo
Arm/Group Description	eszopiclone: 3mg eszopiclone prior to daytime sleep for 3 days (at home) and 1 day (in lab)		eszopiclone: 3mg eszopiclone prior to daytime sleep for 3 days (at home) and 1 day (in lab) placebo: matching placebo prior to daytime sleep for 3 days (at home) and 1 day (in lab)
All Cause Mortality
	Eszopiclone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Eszopiclone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Eszopiclone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/24 (66.7%)		10/24 (41.7%)
Cardiac disorders
Dizziness	2/24 (8.3%)	2	0/24 (0%)	0
Chest pain	1/24 (4.2%)	1	0/24 (0%)	0
Eye disorders
Dry eyes	0/24 (0%)	0	1/24 (4.2%)	1
Tunnel vision	0/24 (0%)	0	1/24 (4.2%)	1
Gastrointestinal disorders
Bad taste	10/24 (41.7%)	10	0/24 (0%)	0
Dry mouth	1/24 (4.2%)	1	1/24 (4.2%)	1
Gagging	0/24 (0%)	0	1/24 (4.2%)	1
General disorders
Headache	6/24 (25%)	7	1/24 (4.2%)	3
Nausea	2/24 (8.3%)	2	0/24 (0%)	0
Application site dryness	0/24 (0%)	0	1/24 (4.2%)	1
Hunger	0/24 (0%)	0	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/24 (0%)	0	2/24 (8.3%)	2
Joint pain	1/24 (4.2%)	1	0/24 (0%)	0
Musculoskeletal pain	1/24 (4.2%)	1	0/24 (0%)	0
Pain in extremities	1/24 (4.2%)	1	0/24 (0%)	0
Leg cramp	0/24 (0%)	0	1/24 (4.2%)	1
Psychiatric disorders
Somnolence	1/24 (4.2%)	2	2/24 (8.3%)	2
Abnormal dreams	1/24 (4.2%)	1	0/24 (0%)	0
Listlessness	0/24 (0%)	0	1/24 (4.2%)	1
Short-term memory loss	0/24 (0%)	0	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/24 (4.2%)	1	0/24 (0%)	0
Sore throat	1/24 (4.2%)	1	0/24 (0%)	0
Head cold	0/24 (0%)	0	1/24 (4.2%)	1
Skin and subcutaneous tissue disorders
Erythema	0/24 (0%)	0	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

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.