Lemborexant Shift Work Treatment Study

Study Overview
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Brief Summary
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Insomnia and daytime sleepiness are common complaints among night shift workers, but effective sleep treatments in shift workers are lacking. The aim of this Phase IV double-blind, placebo-controlled, randomized study is to test whether a dual orexin antagonist, Lemborexant (5mg or 10mg), which would be expected to block the clock-driven orexin-mediated wakefulness during the day, will increase daytime sleep time in shift workers who complain of difficulty sleeping during the daytime compared to placebo.

Detailed Description
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Insomnia and daytime sleepiness are common complaints among night shift workers. A meta-analysis on sleep in shift workers indicates that fixed night shift workers sleep, on average, 0.4 hours less than fixed day shift workers, while rotating shift workers sleep on average 1 hour less than fixed day shift workers. While there may be several reasons for sleep difficulties and sleep loss among shift workers, the misalignment of one's sleep preference (i.e., goal of sleeping during the day) and one's circadian rhythm (i.e., endogenous rhythm that signals the body to be awake during the day) is thought to be a primary cause. Insufficient sleep among night shift and rotating shift workers is linked with significant health consequences, including elevated risk for cardiovascular disease and cancer. Effective sleep treatments in shift workers are lacking. However, a recent randomized study of Suvorexant (20mg), a hypocretin/orexin receptor antagonist, produced a significant improvement in daytime total sleep time compared to placebo. Available evidence suggests that the reason Suvorexant is effective is because it blocks the hypocretin/orexin receptors that mediate signaling from the biological clock (suprachiasmatic nucleus of the hypothalamus) attempting to maintain sustained wakefulness during the biological day. As Lemborexant is also a hypocretin/orexin antagonist, it would also be expected to improve daytime sleep in shift workers but would have the advantage over Suvorexant of being highly effective in the dosages available for clinical use. As such, Lemborexant is ideally positioned to be an effective and important treatment of sleep problems in shift workers. The aim of this Phase IV double-blind, placebo-controlled, randomized study is to test whether a dual orexin antagonist, Lemborexant (5mg or 10mg), which would be expected to block the clock-driven orexin-mediated wakefulness during the day, will increase daytime sleep time in shift workers who complain of difficulty sleeping during the daytime compared to placebo. This will be a 4-week double blinded placebo controlled trial (2 weeks of baseline assessment followed by 2-weeks of treatment/placebo). The trial design is based on a recent successful study of the treatment of sleep problems in shift workers with a hypocretin/orexin receptor antagonist.

Official Title
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Effect of a Dual Orexin Receptor Antagonist, Lemborexant, on Total Sleep Time in Shift Workers: a Randomized Controlled Trial

Conditions
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Shift-Work Related Sleep Disturbance

Intervention / Treatment
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* Drug: Lemborexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full-time night shift work (at least 6 hours per shift, 4 days per week or 32 hours per week) Employed as a night shift worker for at least 3 months Self-reported concerns about daytime sleepiness and difficulty sleeping during the daytime Exclusion Criteria: Pregnancy (verified by urine pregnancy test) or plan to become pregnant in the next 3 months Currently breastfeeding Inadequate opportunity for sleep during the daytime (< 7 hours opportunity) after overnight shift Extreme circadian preference (based on Horne & Ostberg Morningness-Eveningness Questionnaire) Severe depressive symptoms (>25 on CES-D) Unwillingness to discontinue sleep aids (prescription or non-prescription) during the study period Presence of sleep disordered breathing (verified by Apnea link) Self-reported diagnosis of narcolepsy, restless legs syndrome Self-reported intake of >600mg of caffeine per night shift or use of stimulants during night shift, rotational, or irregular shifts Unstable or untreated medical or psychiatric condition based on clinical interview. Severe hepatic or renal impairment (based on chemistry panel); Self-reported use of digoxin or strong or moderate cytochrome P450 3A4 isozyme inhibitors or cytochrome P450 3A4 isozyme inducers for 6 months prior to or during the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a 4-week double blinded placebo controlled trial (2 weeks of baseline assessment followed by 2-weeks of treatment/placebo). The trial design is based on a recent successful study of the treatment of sleep problems in shift workers with a hypocretin/orexin receptor antagonist
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>Participants randomized into this arm will receive Lemborexant (5-10mg). | Drug: Lemborexant<br>* A dual orexin antagonist<br>* Other names: Dayvigo;|
| Placebo Comparator: Placebo Treatment<br>Participants randomized into this arm will receive a placebo medication which appears the same as the active treatment. | Drug: Placebo<br>* A placebo that looks and tastes like Lemborexant tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Daytime Total Sleep Time in Minutes Collected from the Consensus Sleep Diary | Within-person changes in daytime total sleep time in minutes from baseline to 2 weeks. Daytime total sleep time is reported in minutes from a Consensus Sleep Diary, completed by participants daily. | Baseline and 2 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Daytime Total Sleep Time in Minutes Measured by Actigraphy | Within-person changes in daytime total sleep time in minutes from baseline to 2 weeks. Daytime total sleep time is collected using daily actigraphy data from Actiwatches, which participants will wear for two weeks. | Baseline and 2 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shift Work, Daytime Sleepiness, Lemborexant