The Effect of Eszopiclone on the Arousal Threshold in Sleep Apnea Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to find out whether taking eszopiclone (Lunesta) changes the breathing effort required to briefly wake people with obstructive sleep apnea from sleep (respiratory arousal threshold). We would like to see if taking eszopiclone can reduce the severity of obstructive sleep apnea in some people (those that have a low respiratory arousal threshold; i.e. wake up easily to respiratory stimuli).

Detailed Description
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Obstructive sleep apnea is an exceedingly common disease with major neurocognitive and cardiovascular consequences. The current primary treatment e.g. Continuous positive airway pressure (CPAP) is effective but poorly tolerated by many patients particularly those with mild-moderate disease. Secondary treatments such as oral appliances to advance the mandible or surgical procedures to enlarge the airway are commonly appealing to the patient. However, these approaches have only modest success in reducing apnea frequency to an acceptable level. Thus, finding tolerable and effective therapy for sleep apnea remains an important objective. The causes of sleep apnea vary between patients. Targeted therapy according to the underlying causes of sleep apnea in individual patients is likely to be most effective. However, current therapeutic options for sleep apnea are quite limited. The purpose of this physiological research study is to determine if taking eszopiclone (Lunesta)changes the breathing effort required to briefly wake people with obstructive sleep apnea from sleep (the arousal threshold) and if administration of the sedative medication eszopiclone (Lunesta) to certain sleep apnea patients (those with a low arousal threshold ie wake up easily) would be beneficial.

Official Title
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A Double-Blind Randomized Physiological Study Examining the Effects of Eszopiclone on the Arousal Threshold and Obstructive Sleep Apnea Severity

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Eszopiclone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-64 years old Untreated obstructive sleep apnea Exclusion Criteria: Nadir SaO2 <70% on a baseline PSG Medications known to affect either sleep, breathing or muscle activity Major co-morbidities apart from sleep apnea Allergy to lidocaine, oxymetazoline HCl, or eszopiclone Women who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Eszopiclone<br>Eszopiclone 3mg prior to sleep (1 night) | Drug: Eszopiclone<br>* 3mg tablet once prior to sleep<br>* Other names: Lunesta;|
| Placebo Comparator: Sugar Pill<br>Sugar Pill (placebo) prior to sleep (1 night) | Drug: Placebo<br>* 1 placebo capsule prior to sleep<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea Hypopnea Index | number of respiratory events per hour of sleep Respiratory events last for at least 10 seconds and are associated with a decrease in blood oxygenation or a cortical arosual from sleep. AHI values are typically categorized as 5-15/hr = mild; 15-30/hr = moderate; and > 30/h = severe | 8 hour In-Laboratory Polysomnogram (PSG) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arousal Threshold | quantified using an epiglottic pressure transducer in CmH2O | 8 hour In-Laboratory Polysomnogram (PSG) | 
| Nadir Overnight Oxygen Saturation | Nadir overnight oxygen saturation (%) | 8 hour In-Laboratory Polysomnogram (PSG) | 
| Sleep Duration | total sleep duration | 8 hour In-Laboratory Polysomnogram (PSG) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obstructive sleep apnea, Arousal threshold, Sedative medication, upper airway