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Effects of Lemborexant as a Treatment for Moderate-to-severe OSA Patients With Low Arousal Threshold

Phase 1
Recruiting
Conditions
OSA
Interventions
Registration Number
NCT05763329
Lead Sponsor
Chulalongkorn University
Brief Summary

The goal of this randomized, placebo-controlled, double-blind, crossover trial (1-week wash out period) is to compare 1 night of 5 mg Lemborexant to placebo administered before sleep in 10 moderate to severe OSA patients with low arousal threshold

The main questions it aims to answer are:

1. The effect of Lemborexant on apnea/hypopnea index (AHI) in moderate-to-severe OSA patients with low arousal threshold.

2. The effect of Lemborexant on the following parameters in moderate-to-severe OSA patients with low arousal threshold.

* Arousal threshold

* Mean and nadir oxygen saturation

* Sleep latency

* Sleep efficiency

* Wake after sleep onset (WASO)

* Percentage of time spent in NREM stage 1-3 and REM stage

* Stanford Sleepiness Scale Questionnaire in the morning

* The Oxford Sleep Resistance Test (OSLER) test

Participants will

* complete two overnight in-laboratory polysomnography (1-week washout)

* complete the OSLER test in the morning of the two overnight test

Researchers will compare with the placebo group to see if there is a difference in AHI

Detailed Description

Research Design A randomized, placebo-controlled, double-blind, crossover trial (1-week wash out period) comparing 1 night of 5 mg Lemborexant to placebo administered before sleep.

Research Methodology Participants A total of 10 moderate to severe OSA patients with low arousal threshold are randomized 1:1 to either Lemborexant or placebo. The participants will complete two overnight in-laboratory polysomnography (1-week washout). Next-morning alertness will also be assessed using OSLER test, respectively.

Inclusion criteria

Eligible, healthy individuals with all the followings:

* Untreated OSA patient 18 - 65 years of age

* AHI ≥15 events/h of sleep

* Low arousal threshold

Study protocol All patients who were previously diagnosed with moderate to severe obstructive sleep apnea from baseline polysomnography with a low arousal threshold will be enrolled.

The patients will be subsequently randomized 1:1 to one of the two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period. Patients will receive either Lemborexant 5 mg per day or placebo prior 5 minutes before lights-out.

During this 2-night polysomnography, sleep parameters will be analyzed including AHI, mean and nadir oxygen indices, sleep latency, sleep efficiency, wake after sleep onset (WASO), and percentage of time spent in NREM, stage 1-3 and REM stage. The OSLER test to define vigilance will be obtained on the following morning.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
10
Inclusion Criteria
  • Untreated OSA patient 18 - 65 years of age(49)
  • AHI ≥15 events/h of sleep (moderate to severe)(23, 49)
  • Low arousal threshold was defined using previously recommended criteria which allocated a score of 1 to each criterion that was satisfied: (apnea-hypopnea index, <30 events per hour) + (nadir oxygen saturation as measured by pulse oximetry >82.5%) + (fraction of hypopneas >58.3%). A score of 2 or above defined a low arousal threshold(50) (low arousal threshold defined as esophageal pressure values are 0 to -15 cmH2O)(27)
Exclusion Criteria
  • Previous allergy or adverse effects with Lemborexant or other sedatives - Taking any medication that affects sleep or other variable measured in this study - Pregnant or nursing mothers - Respiratory disorders other than OSA - Comorbid disease of poor controlled or resistant hypertension, uncontrolled cardiovascular or cerebrovascular disease
  • Using CPAP or other dental devices
  • Unable to tolerate equipment in this study

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo Day 1Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive placebo 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the Lemborexant arm and receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.
PlaceboLemborexant 5 MG Oral Tablet [Dayvigo] Day 2Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive placebo 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the Lemborexant arm and receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.
LemborexantLemborexant 5 MG Oral Tablet [Dayvigo] Day 1Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the placebo arm and receive placebo 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.
LemborexantPlacebo Day 2Patients will receive two treatment sequences. Participants will complete two overnight sleep studies and cross-over with 1-week wash-out period The participants will receive Lemborexant 5 mg per day 5 minutes before lights-out for one dose for the first overnight sleep test of the experiment. After 1 week wash-out period, the participants will cross to the placebo arm and receive placebo 5 minutes before lights-out for one dose for the second overnight sleep test of the experiment.
Primary Outcome Measures
NameTimeMethod
apnea/hypopnea index (AHI)through study completion, one week

AHI

Secondary Outcome Measures
NameTimeMethod
Mean and nadir oxygen saturationthrough study completion, one week
Sleep latency (Time the patients fall asleep)through study completion, one week

Time spent from light out to the first 20 consecutive 30-second period of nonwakefulness (minutes)

Sleep efficiency (Time the patients actually sleep through out the experiment)through study completion, one week

Time the patient sleep per time in bed which is the total sleep time per time from light out until light on (total record time (TRT) (8 hours) (minutes)

Wake after sleep onset (WASO)through study completion, one week

Total time of wakefulness after initial sleep onset until light on

Percentage of time spent in NREM stage 1-3 and REM stagethrough study completion, one week
The Oxford Sleep Resistance Test (OSLER) testthrough study completion, one week

Trial Locations

Locations (1)

Chulalongkorn University

🇹🇭

Pathum Wan, Bangkok, Thailand

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