The Impact of Venlafaxine on Apnea Hypopnea Index 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 randomized double-blinded crossover pilot study. The investigators will test whether Venlafaxine has important effects on the apnea hypopnea index. Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) for the treatment of depression and anxiety. Venlafaxine increases serum serotonin level, which may affect arousal threshold. Furthermore, higher serotonin level theoretically may improve muscle tone, including upper airway muscle. Therefore, the investigators hypothesize that venlafaxine may decrease arousal threshold and improve muscle tone, leading to improvement of OSA. Eligible participants will undergo overnight polysomonography as described below and will receive either Venlafaxine(50 mg 2 hour prior to sleep) or placebo (in random order) followed roughly 7 days later with placebo or donepezil. This aim will allow us to test the impact of Venlafaxine on the apnea hypopnea index. The change in apnea hypopnea index will be compared in the Venlafaxine groups with the placebo group.

Official Title
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The Impact of Venlafaxine on Apnea Hypopnea Index in Patients With Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Venlafaxine
* 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 cardiac (apart from treated hypertension), pulmonary (including uncontrolled asthma), renal, neurologic (including epilepsy), neuromuscular, or hepatic disease. Susceptible to stomach ulcers. co-administration of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing the MAO inhibitor); initiation of MAO inhibitor intended to treat psychiatric disorders within 7 days of discontinuing venlafaxine; initiation in patients receiving linezolid or intravenous methylene blue Pregnant women. History of hypersensitivity to Afrin, Lidocaine (all Aims) or venlafaxine History of bleeding diathesis and/or gastrointestinal bleeding. Glaucoma and Urinary Retention Use of any medications that may affect sleep or breathing. Use of any medications that have known interaction with venlafaxine and the interaction may significantly increase the risk of the subject or decrease the therapeutic effect of the medication. 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. Desaturations to below 70% lasting greater than 10 seconds in duration per event

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 |
| --- | --- |
| Active Comparator: Venlafaxine<br>50mg of Venlafaxine before sleep | Drug: Venlafaxine<br>* Venlafaxine 50mg before sleep<br>|
| Placebo Comparator: Placebo<br>One piece of placebo before sleep | 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 |
| --- | --- | --- |
| The Apnea Hypopnea Index | The Apnea hypopnea index 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 change from baseline in apnea hypopnea index after a single dose of Venlafaxine will be evaluated using overnight polysomnography. An apnea hypopnea index less than five events per hour is considered within normal limits. | Baseline and 7-day follow up | 
| Nadir Oxygen Level During Sleep | Change from baseline in nadir oxygen level during sleep after a single dose of Venlafaxine will be evaluated using overnight polysomnography. A lower blood oxygen saturation during sleep is associated with a more severe obstructive sleep apnea. | Baseline and 7-day follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Loop Gain | Loop gain 1 is used to describe the stability of ventilatory control. The change from baseline in loop gain after a single dose of Venlafaxine will be estimated. | Baseline and 7-day follow up | 
| Arousal Threshold | Change from baseline in respiratory arousal threshold after single dose of Venlafaxine will be estimated. | Baseline and 7-day follow up | 
| Sleep Efficiency | Change from baseline in sleep efficiency after single dose of Venlafaxine will be estimated using overnight polysomnography. | Baseline and 7-day follow up | 

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