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

OSA Clinical Trial

— LOSALAT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05763329
• Other study ID #: 218/64
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2023
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: Chulalongkorn University
• Contact: Sarocha Vivatvakin, MD
• Phone: 66879310233
• Email: sarocha.v[@]chula.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

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), 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• OSA

Intervention

Drug:
• Lemborexant 5 MG Oral Tablet [Dayvigo] Day 1
Patients will receive Lemborexant 5 mg per day on the first day of sleep test
• Lemborexant 5 MG Oral Tablet [Dayvigo] Day 2
Patients will receive Lemborexant 5 mg per day on the second day of sleep test
• Placebo Day 1
Patients will receive placebo on the first day of sleep test
• Placebo Day 2
Patients will receive placebo on the second day of sleep test

Locations

Country	Name	City	State
Thailand	Chulalongkorn University	Pathum Wan	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Chulalongkorn University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	apnea/hypopnea index (AHI)	AHI	through study completion, one week
Secondary	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
Secondary	Mean and nadir oxygen saturation		through study completion, one week
Secondary	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
Secondary	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
Secondary	Wake after sleep onset (WASO)	Total time of wakefulness after initial sleep onset until light on	through study completion, one week
Secondary	Percentage of time spent in NREM stage 1-3 and REM stage		through study completion, one week
Secondary	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
Secondary	The Oxford Sleep Resistance Test (OSLER) test		through study completion, one week