Shift-Work Sleep Disorder
Conditions
Keywords
Shift-work, SWSD, eszopiclone, MWT, shiftworkers
Brief summary
The purpose of this study is to test the effects of eszopiclone on daytime sleep and overnight wakefulness in shift workers.
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.
Interventions
DRUGeszopiclone
3mg eszopiclone prior to daytime sleep for 3 days (at home) and 1 day (in lab)
DRUGmatching placebo
matching placebo prior to daytime sleep for 3 days (at home) and 1 day (in lab)
Sponsors
Sumitomo Pharma America, Inc.
Massachusetts General Hospital
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 50 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Eszopiclone Then Placebo Study participants on eszopiclone and then placebo | 11 |
| Placebo Then Eszopiclone Study participants on placebo and then eszopiclone | 13 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | disempanelled for inappropriate behavior | 1 | 0 |
Baseline characteristics
| Characteristic | Eszopiclone Then Placebo | Placebo Then Eszopiclone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 13 Participants | 24 Participants |
| Region of Enrollment United States | 11 participants | 13 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 24 | 10 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
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.
Time frame: On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Eszopiclone | Nighttime Wakefulness Assessed by Mean Sleep Latency Across 4 Maintenance of Wakefulness Tests | 11.0 minutes |
| Placebo | Nighttime Wakefulness Assessed by Mean Sleep Latency Across 4 Maintenance of Wakefulness Tests | 14.75 minutes |
Secondary
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.
Time frame: On each treatment, during an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | EEG-recorded Sleep Efficiency | 92.3 percentage of time sleeping | Standard Deviation 5.1 |
| Placebo | EEG-recorded Sleep Efficiency | 88.9 percentage of time sleeping | Standard Deviation 9.6 |
Secondary
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.
Time frame: On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Objective Vigilance Task Performance | 631 milliseconds | Standard Deviation 260.5 |
| Placebo | Objective Vigilance Task Performance | 617 milliseconds | Standard Deviation 294.9 |
Secondary
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.
Time frame: On each treatment, after an 8.5 hour daytime sleep period following at least 3 consecutive night shifts
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Sleep-dependent Memory Consolidation | 20.4 words | Standard Deviation 8.1 |
| Placebo | Sleep-dependent Memory Consolidation | 21.4 words | Standard Deviation 6.7 |
Secondary
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.
Time frame: On each treatment, after an 8.5-hr daytime sleep episode following at least 3 consecutive night shifts
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eszopiclone | Subjective Sleepiness and Performance | 5.0 units on a scale | Standard Error 2.1 |
| Placebo | Subjective Sleepiness and Performance | 5.3 units on a scale | Standard Error 2.3 |