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

Study Overview
=================
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 20 moderate to severe OSA patients with low arousal threshold The main questions it aims to answer are: The effect of Lemborexant on apnea/hypopnea index (AHI) in moderate-to-severe OSA patients with low arousal threshold. 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), with esophageal pressure catheter placement and standard polysomnography monitoring complete the Stanford Sleepiness Scale Questionnaire and 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 20 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), with esophageal pressure catheter placement and standard polysomnography monitoring. Next-morning sleepiness and alertness will also be assessed using Stanford Sleepiness Scale Questionnaire and 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, arousal threshold, 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 Stanford Sleepiness Scale Questionnaire to define sleepiness and OSLER test to define vigilance will be obtained on the following morning.

Official Title
-----------------
A Randomized, Double-blind, Placebo-Controlled Trial on the Effects of Lemborexant as a Treatment for Moderate-to-severe OSA Patients With Low Arousal Threshold

Conditions
-----------------
OSA

Intervention / Treatment
-----------------
* Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1
* Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2
* Drug: Placebo Day 1
* Drug: Placebo Day 2


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 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. Time of lights out was calculated from the median usual bedtime for each participant from the most recent 5 days (± 1 hour) and was kept constant between the two study nights. During this 2-night polysomnography, sleep parameters will be analyzed. The Stanford Sleepiness Scale Questionnaire to define sleepiness and OSLER test to define vigilance will be obtained on the following morning.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lemborexant<br>Patients 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. | Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1<br>* Patients will receive Lemborexant 5 mg per day on the first day of sleep test<br>Drug: Placebo Day 2<br>* Patients will receive placebo on the second day of sleep test<br>|
| Placebo Comparator: Placebo<br>Patients 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. | Drug: Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2<br>* Patients will receive Lemborexant 5 mg per day on the second day of sleep test<br>Drug: Placebo Day 1<br>* Patients will receive placebo on the first day of sleep test<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| apnea/hypopnea index (AHI) | AHI | through study completion, one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal pressure to measure arousal threshold | The arousal threshold is calculated from the average of nadir esophageal pressure immediately prior to the arousal of each apnea or hypopnea events | through study completion, one week | 
| Mean and nadir oxygen saturation |  | through study completion, one week | 
| Sleep latency (Time the patients fall asleep) | Time spent from light out to the first 20 consecutive 30-second period of nonwakefulness (minutes) | through study completion, one week | 
| Sleep efficiency (Time the patients actually sleep through out the experiment) | 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) | through study completion, one week | 
| Wake after sleep onset (WASO) | Total time of wakefulness after initial sleep onset until light on | through study completion, one week | 
| Percentage of time spent in NREM stage 1-3 and REM stage |  | through study completion, one week | 
| Stanford Sleepiness Scale (SSS) Questionnaire in the morning | The questionnaire consists of only one item that requires the patients to select one of the seven statements that best described their sleepiness (scale of one is fully awake (best) and seven is sleepiness (worst) feeling active, vital, alert, or wide awake functioning at high levels, but not at peak; able to concentrate awake, but relaxed; responsive but not fully alert somewhat foggy, let down foggy; losing interest in remaining awake; slowed down sleepy, woozy, fighting sleep; prefer to lie down No longer fighting sleep, sleep onset soon; having dream-like thoughts | through study completion, one week | 
| The Oxford Sleep Resistance Test (OSLER) test |  | through study completion, one week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Apnea/Hypopnea Index (AHI), Lemborexant, Obstructive Sleep Apnea (OSA), Low Arousal Threshold, Polysomnography