OSA - Obstructive Sleep Apnea
Conditions
Keywords
Apnea/Hypopnea Index (AHI), Lemborexant, Obstructive Sleep Apnea (OSA), Low Arousal Threshold, Polysomnography
Brief summary
The goal of this clinical trial is to investigate the 1-month treatment effects of different dose of lemborexant in moderate OSA adult patients (18-65 years of age) with low arousal threshold. The main questions it aims to answer are: Primary outcome measure: Apnea/hypopnea index (AHI) Secondary outcome measure: 1. Polysomnography parameters * Mean and nadir oxygen saturation * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Rapid eye movement (REM) latency * Percentage of time spent in Non-rapid eye movement (NREM) stage 1-3 and REM stage * Arousal index 2. Oxford Sleep Resistance Test (OSLER) test 3. Epworth Sleepiness Scale (ESS) 4. Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) 5. Pittsburgh Sleep Quality Index (PSQI) 6. Actigraphy parameters * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency 7. Sleep diary parameters (Appendix 5) * Total sleep time * Sleep efficiency * Wake after sleep onset (WASO) * Sleep latency * Sleep quality Researchers will compare placebo to see if there is a difference in AHI. Participants will * participate a total of 3 phases of study (3-crossover trial) * each phrase the participants will receive either lemborexant 5 mg, lemborexant 10 mg, or placebo orally per day for 30 days with 2-week washout (depend on intervention arm whether the participants receive which intervention sequence) * complete three overnight in-laboratory polysomnography (2-week washout) at day 30 of each phrase * monitor actigraphy during day 1 to 29 of intervention of all periods * record sleep diary during day 1 to 29 of intervention of all periods * complete the OSLER test in the morning of the three overnight test * complete questionnaires including: Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T), Pittsburgh Sleep Quality Index (PSQI) at baseline (prior to intervention) and the night before overnight in-laboratory polysomnography
Interventions
DRUGLemborexant 5 MG [Dayvigo] Period 1
Participants will receive lemborexant 5 mg per day for 30 days during first period
DRUGPlacebo Period 1
Participants will receive placebo 5 mg per day for 30 days during the first period
DRUGLemborexant 5 MG [Dayvigo] Period 2
Participant will receive lemborexant 5 mg per day for 30 days during the second period
DRUGPlacebo Period 2
Participant will receive placebo 5 mg per day for 30 days during the second period
DRUGLemborexant 5 MG [Dayvigo] Period 3
Participants will receive lemborexant 5 mg per day for 30 days during third period
DRUGPlacebo Period 3
Participants will receive placebo per day for 30 days during third period
DRUGLemborexant 10 MG [Dayvigo] Period 1
Participants will receive lemborexant 10 mg per day for 30 days during first period
DRUGLemborexant 10 MG [Dayvigo] Period 2
Participants will receive lemborexant 10 mg per day for 30 days during second period
DRUGLemborexant 10 MG [Dayvigo] Period 3
Participants will receive lemborexant 10 mg per day for 30 days during third period
Sponsors
Chulalongkorn University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Individuals are eligible for participation in this study if they have all of the followings: 1. Patient, aged 18 - 65 years at the time of informed consent 2. Voluntary agreement and capable for giving written informed consent 3. Diagnosis with OSA according to the criteria of the International Classification of Sleep Disorders, version 3 Text Revision 4. Baseline screening polysomnography (PSG) demonstrated apnea-hypopnea index 15 - 30 events/h of sleep (moderate severity) 5. Patients identified as low arousal threshold using previously recommended criteria which allocated a score of 1 to each criterion: apnea-hypopnea index \< 30 events per hour, nadir oxygen saturation as measured by pulse oximetry \> 82.5%, and fraction of hypopneas \> 58.3%. A score of 2 or above defined a low arousal threshold. 6. Peripheral capillary oxygen saturation (SpO2) ≥ 94% measured during screening visit 7. Habitually sleeping ≥ 5.5 hours/night with usual bedtime falls within the range of 9:00 PM to 1:00 AM 8. Body mass index 18 - 40 kg/m2
Exclusion criteria
Individuals were not eligible for participation in this study if they have any of the followings: 1. Previous allergy or adverse effects with Lemborexant or other sedatives 2. Pregnant or breastfeeding 3. Significant medical comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion 4. Uncontrolled cardiovascular or cerebrovascular diseases 5. Neuromuscular diseases 6. Nasal anatomical defect 7. Significant psychiatric comorbidities that could affect individual safety and study assessment results, regarding investigators' opinion 8. Active respiratory disorders other than OSA 9. Central respiratory events (CAHI) \>25% of the total AHI 10. Diagnosis/symptoms of sleep-related disease other than OSA including narcolepsy, restless legs syndrome, periodic limb movement disorder, or circadian rhythm sleep-wake disorder 11. Severe hypersomnolence (ESS ≥16) 12. Peripheral capillary oxygen saturation (SpO2) \< 80% for ≥ 5% of total sleep time measured during screening visit 13. Driving-related sleepiness accident or near misses in the past 12 months 14. Safety-critical occupation 15. Using CPAP or other dental devices within 2 weeks of screening polysomnography until the end of the study 16. Unable to tolerate equipment in this study 17. Taking any medication that affects sleep or other variable measured in this study 18. Taking any medication with cytochrome P450 Family 3A (CYP3A) inhibitors and all CYP3A inducers 19. Drug or alcohol use disorder within 2 years before the study initiation or current excessive alcohol intake 20. Excessive caffeine intake
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apnea/hypopnea index (AHI) | At day 30 during the overnight in-laboratory of each study period | Apnea/hypopnea index (AHI) measured by polysomnography (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean and nadir oxygen saturation | At day 30 during the overnight in-laboratory of each study period | Mean and nadir oxygen saturation measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores mean better outcome) |
| Sleep efficiency | At day 30 during the overnight in-laboratory of each study period | Sleep efficiency measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores mean better outcome) |
| Wake after sleep onset (WASO) | At day 30 during the overnight in-laboratory of each study period | Wake after sleep onset (WASO) measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome) |
| Sleep latency | At day 30 during the overnight in-laboratory of each study period | Sleep latency measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome) |
| REM latency | At day 30 during the overnight in-laboratory of each study period | REM latency measured by polysomnography (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean worse outcome) |
| Percentage of time spent in NREM stage 1-3 and REM stage | At day 30 during the overnight in-laboratory of each study period | Percentage of time spent in NREM stage 1-3 and REM stage measured by polysomnography (scale: percent: minimum 0% - maximum 100%; higher scores in NREM stage 3 and REM mean better outcome but higher scores in NREM stage 1 and 2 mean worse outcome) |
| Arousal index | At day 30 during the overnight in-laboratory of each study period | Arousal index measured by polysomnography (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome) |
| OSLER error index | On the morning of the in-laboratory polysomnography | Oxford Sleep Resistance Test (OSLER) test (scale: events/hour: minimum 0 event/hour - no maximum scoring; higher scores mean worse outcome) |
| Epworth Sleepiness Scale (ESS) | Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period | Epworth Sleepiness Scale (ESS) questionnaires (scale: point: minimum 0 point - maximum 24 point; higher scores mean worse outcome) |
| Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) | Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period | Functional Outcome of Sleep Questionnaire-short version (FOSQ-10T) (scale: point: minimum 5 point - maximum 20 point; higher scores mean better outcome) |
| Pittsburgh Sleep Quality Index | Baseline (prior to intervention) and at day 30 of intervention before the overnight in-laboratory of each study period | Pittsburgh Sleep Quality Index (scale: point: minimum 0 point - maximum 21 point; higher scores mean worse outcome) |
| Total sleep time | During day 1-29 of intervention | Total sleep time measured by actigraphy (scale: minute: minimum 0 minute - no maximum scoring; higher scores mean better outcome) |
| Sleep quality | During day 1-29 of intervention | Sleep quality recorded by sleep diary (5-point Likert scale of 1-5; higher score mean better outcome) |
Countries
Thailand
Contacts
CONTACTSarocha Vivatvakin, MD
CONTACTNaricha Chirakalwasan, MD
PRINCIPAL_INVESTIGATORSarocha Vivatvakin, MD
Department of Medicine, Faculty of Medicine
Outcome results
None listed