Lemborexant Shift Work Treatment Study

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

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.

Study Overview

• Status: Recruiting
• Conditions: Shift-Work Related Sleep Disturbance
• Intervention / Treatment: Drug: Lemborexant; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cara A Woodworth, BA; Phone Number: 415-476-6618; Email: cara.woodworth@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Cara A Woodworth, BA; Phone Number: 415-476-6618; Email: cara.woodworth@ucsf.edu
      • Sub-Investigator: Andrew Krystal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Aric Prather, PhD, University of California, San Francisco

Publications and helpful links

Helpful Links

• Study Screener

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2022
• Primary Completion (ANTICIPATED): June 30, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (ACTUAL): April 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Lemborexant; Shift Work; Daytime Sleepiness
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Dyssomnias; Parasomnias; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Lemborexant
• Other Study ID Numbers: 20-32763

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No