Clinical trial NCT05763329: Effects of Lemborexant as a Treatment for Moderate-to-severe OSA Patients With Low Arousal Threshold
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: OSA
Keywords: Apnea/Hypopnea Index (AHI)
Lemborexant
Obstructive Sleep Apnea (OSA)
Low Arousal Threshold
Polysomnography
Lead sponsor: Chulalongkorn University
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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 OSLER test to define vigilance will be obtained on the following morning.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: apnea/hypopnea index (AHI)
timeFrame: through study completion, one week
Secondary outcomes:
measure: Mean and nadir oxygen saturation
timeFrame: through study completion, one week
measure: Sleep latency (Time the patients fall asleep)
timeFrame: through study completion, one week
measure: Sleep efficiency (Time the patients actually sleep through out the experiment)
timeFrame: through study completion, one week
measure: Wake after sleep onset (WASO)
timeFrame: through study completion, one week
measure: Percentage of time spent in NREM stage 1-3 and REM stage
timeFrame: through study completion, one week
measure: The Oxford Sleep Resistance Test (OSLER) test
timeFrame: through study completion, one week
Other outcomes:
Locations:
city: Pathum Wan
country: Thailand
facility: Chulalongkorn University
state: Bangkok
Study officials:
affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University
name: Sarocha Vivatvakin, MD
role: PRINCIPAL_INVESTIGATOR
References: