The Impact of Arousal Threshold in Obstructive Sleep Apnea

Study Overview
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Brief Summary
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The investigators hypothesis is that obstructive sleep apnea (OSA) patients with a low arousal threshold may wake up too early during a respiratory event, before upper airway muscles can be activated to achieve stable ventilation. Thus, strategies to manipulate the respiratory arousal threshold could potentially improve the quality of sleep and sleep disordered breathing. Agents that raise arousal threshold are therefore likely to benefit some patients with OSA. The overall goal of this project is to determine the importance of the arousal threshold in OSA, determine which patients might benefit from a raised arousal threshold, and test this hypothesis by using pharmacological manipulation of the arousal threshold to achieve this goal.

Detailed Description
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This study is a pilot study. The investigators will test whether donepezil has important effects on the arousal threshold and on the apnea hypopnea index. Donepezil is a cholinesterase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of symptoms of Alzheimer's disease. Eligible participants will undergo overnight polysomonography as described below and will receive either donepezil (10 mg immediately prior to sleep) or placebo (in random order) followed roughly 14 days later with placebo or donepezil. This aim will allow us to test the impact of donepezil on the apnea hypopnea index. The study plans to enroll approximately 30 subjects. The change in apnea hypopnea index as well as arousal thresholds/upper airway mechanics will be compared in the donepezil groups with the placebo group.

Official Title
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The Impact of Arousal Threshold in Obstructive Sleep Apnea: Donepezil's Effects on the Arousal Threshold and on the Apnea Hypopnea Index

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Donepezil
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-70 years sleep study (with apnea hypopnea index>5) Diagnosis of obstructive sleep apnea Exclusion Criteria: Any known unstable cardiac (apart from treated hypertension), pulmonary (including asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease. Susceptible to stomach ulcers. Pregnant women or Nursing mothers Using positive airway pressure (PAP) therapy over one week or longer Body weight <55kg History of hypersensitivity to Afrin, Lidocaine and/or Donepezil History of bleeding diathesis and/or gastrointestinal bleeding. Use of any medications that may affect sleep or breathing. A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders. Substantial cigarette (>5/day), alcohol (>3oz/day) or use of illicit drugs. More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day. Deprived from sleep in the recent one week Desaturations to below 70% lasting greater than 10 seconds in duration per event in the sleep study (without Oxygen).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br>Sleep data with Donepezil given | Drug: Donepezil<br>* Donepezil 10mg before sleep<br>|
| Placebo Comparator: Placebo<br>Sleep data with Placebo given | Drug: placebo<br>* One piece of placebo before sleep<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea Hypopnea Index (AHI) | The Apnea-Hypopnea Index or Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. The apneas (pauses in breathing) must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A higher AHI value indicates more severe sleep apnea | 14 days (during overnight sleep study after donepezil or placebo is given) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Arousal Threshold | Arousal Threshold was measured as the average nadir epiglottic airway pressure immediately before electroencephalogram (EEG) arousal. It was measured with an epiglottic pressure catheter. The epiglottic catheter/balloon is linked in a pressure catheter inserted through the de-congested, anesthetized nostril and the tip of the catheter located at hypopharyngeal area. | 14 days (during overnight sleep study after donepezil or placebo is given) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obstructive, Sleep Apnea, Arousal threshold, Donepezil