Effects of Quetiapine on Sleep and Next Day Alertness in People With Obstructive Sleep Apnea

Study Overview
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Brief Summary
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Quetiapine is medication used to treat schizophrenia and bipolar disorder. Increasingly, low doses of quetiapine are prescribed off-label for insomnia. Quetiapine increases sleep duration with fewer interruptions, and people report feeling more rested. This accounts for why it is popular to prescribe for insomnia. Insomnia and obstructive sleep apnea (OSA) share many symptoms and differential diagnosis can be difficult. While quetiapine may improve sleep and breathing in certain people (i.e in light sleepers) an initial study indicated that quetiapine caused breathing disturbances in healthy individuals. Effects in OSA are unknown. In this placebo-controlled double blind study, participants with mild-moderate OSA will spend 2 nights in the sleep lab, one with quetiapine at a dose commonly prescribed for insomnia and one with placebo. The investigators will assess participants sleep by standard clinical sleep study, and morning alertness using questionnaires, reaction tests, and a driving simulator test.

Official Title
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Effects of Quetiapine on Sleep and Next Day Alertness in People With Obstructive Sleep Apnea

Conditions
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Sleep Apnea, Obstructive

Intervention / Treatment
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* Drug: Quetiapine 50 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages: 18+ (Adult, Older Adult) Gender: All Moderate or more difficulty staying asleep score on the Insomnia Severity Index questionnaire Obstructive Sleep Apnoea (OSA), Apnoea Hypopnea Index ≥ 5 events/hour BMI between 18.5 and 40 kg/m2 Exclusion Criteria: Concomitant medications that interact or are contraindicated with quetiapine Concomitant medications known to influence breathing, sleep, arousal, or muscle physiology Current pregnancy or breast-feeding Current or recent other medical conditions likely to affect results or safety

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind, randomized, placebo-controlled, cross-over study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine<br>Quetiapine 50mg in the form of one capsule, taken before bedtime. Dosage is taken on one instance for one night only. | Drug: Quetiapine 50 MG<br>* A single dose of 50mg of quetiapine taken at bedtime for one night.<br>* Other names: Seroquel;|
| Placebo Comparator: Placebo<br>Placebo sugar pill in the form of one capsule, taken before bedtime. Dosage is taken on one instance for one night only. | Drug: Placebo<br>* A placebo sugar pill that looks like the quetiapine tablet taken at bedtime for one night.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in OSA severity (Quetiapine night vs. placebo night) | OSA severity as measured by the AHI (apnoea hypopnea index measured as # events/h sleep) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nadir overnight hypoxemia (Quetiapine night vs. placebo night) | Nadir overnight oxygen saturation during sleep (%) measured via pulse oximetry during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in mean overnight hypoxemia (Quetiapine night vs. placebo night) | Mean overnight oxygen saturation during sleep (%) measured via pulse oximetry during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in time below 90% blood arterial oxygen saturation (Quetiapine night vs. placebo night) | Percent time asleep spent below an arterial oxygen saturation of 90% measured via pulse oximetry during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in sleep efficiency (Quetiapine night vs. placebo night) | Percent time spent asleep divided by the recording time from lights out to lights on during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in arousal index (Quetiapine night vs. placebo night) | Number of cortical arousals per hour of sleep during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in sleep architecture (Quetiapine night vs. placebo night) | Proportion of sleep stages (% total sleep time) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in respiratory control (Quetiapine night vs. placebo night) | Loop gain and the ventilatory response to arousal (% eupnea) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in the respiratory arousal threshold (Quetiapine night vs. placebo night) | Threshold to arousal (% eupnea) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in airway collapsibility (Quetiapine night vs. placebo night) | Vpassive (% eupnea) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in pharyngeal muscle response (Quetiapine night vs. placebo night) | Vcompensation (% eupnea) during overnight in-laboratory polysomnography. | Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Baseline OSA endotypes (outcomes 8-11) and whether they are associated with changes in OSA severity (Quetiapine night vs. placebo night) | Exploratory analysis to determine if baseline OSA endotypes (outcomes 8-11) are associated with changes in OSA severity (Quetiapine night vs. placebo night) | Baseline sleep study | 
| Change in perceived sleepiness (Quetiapine night vs. placebo night) | Next day perceived sleepiness assessed via the Karolinska Sleepiness Scale (10 point scale where 1=extremely alert and 10=extremely sleepy) | Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in driving simulator performance (Quetiapine night vs. placebo night) | Next day alertness as measured via the AusEd driving simulator performance task | Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 
| Change in psycho-motor vigilance (Quetiapine night vs. placebo night) | Next day alertness as measured via the pschomotor vigilance test (PVT) | Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep apnea, obstructive, quetiapine, randomised, double-blind, placebo, respiratory arousal threshold