Sleep and Breathing in the General Population - Chemical Stimuli

Study Overview
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Brief Summary
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Central sleep apnea (CSA) is a common condition and its treatment remains elusive. The focus of this proposal is to identify the role of the physiologic path involving cortical arousals in CSA by decreasing arousal frequency using the pharmacological agent zolpidem. The goal is to identify the acute effects of administering zolpidem on sleep and respiratory outcomes, and subsequently, its effect on the severity of CSA and propensity to develop CSA. This study will shed light on the mechanisms underlying CSA that involve cortical arousals and will guide future therapeutic interventions for CSA.

Detailed Description
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The literature suggests that zolpidem may be effective in the treatment of central sleep apnea (CSA). However, evidence regarding the efficacy of zolpidem and the underlying mechanisms involved in its effect on CSA are not well-studied. Furthermore, respiratory-related arousals are hypothesized to contribute CSA symptoms and severity. The aim of the study is to determine the effect of decreasing respiratory-related arousals on the propensity to develop central apnea. The investigators hypothesize that administration of the nonbenzodiazepine hypnotic zolpidem will decrease the frequency of respiratory-related arousals, lower the central apnea-hypopnea index, and widen the CO2 reserve during sleep in patients with CSA compared to no treatment. Participants will complete a night study on a low dose of zolpidem and another night study without zolpidem in a crossover manner. The order of night studies is randomized. The results will help unveil the role of arousals in CSA and the acute effect of zolpidem on CSA severity and the propensity to CSA.

Official Title
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Sleep and Breathing in Health and Disease (Part 2A - Chemical Stimuli, Sleep and Breathing in the General Population)

Conditions
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Sleep-disordered Breathing

Intervention / Treatment
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* Drug: Zolpidem
* Other: No Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Veterans with central sleep apnea, defined as Apnea Hypopnea Index (AHI)>15/hour with CAHI>5/hour, will be included in the experiments. Exclusion Criteria: less than 18 years old pregnant or breastfeeding female have severe respiratory disease that require to be on oxygen recent health event that may affect the ability to participate in the study, Body Mass Index (BMI) is >40 kg/m2 significant insomnia mental instability recent health event that may affect sleep if at any time the principal investigator (PI) identifies that a certain drug is not suitable, or are unable to use the device that is used to treat sleep apnea, will be not be allowed to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: After an initial assessment to determine eligibility, participant complete two in-lab night studies in a randomized manner including one night with the administration of zolpidem and another without zolpidem.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zolpidem, then No Treatment<br>Participants will be administered zolpidem for the first night study, and No Treatment during the second night study. | Drug: Zolpidem<br>* A nonbenzodiazepine hypnotic<br>* Other names: Ambien;Other: No Treatment<br>* The Control condition in which participants do not receive medication.<br>|
| Experimental: No Treatment, then Zolpidem<br>Participants will be administered zolpidem for the second night study, and No Treatment during the first night study. | Drug: Zolpidem<br>* A nonbenzodiazepine hypnotic<br>* Other names: Ambien;Other: No Treatment<br>* The Control condition in which participants do not receive medication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Central Apnea-hypopnea Index | The number of central apneas and hypopneas per hour of sleep was obtained from polysomnography studies. | one night | 
| Respiratory Arousal Index | A measure of the frequency of respiratory-related arousals during sleep | one night | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CO2 Reserve | CO2 reserve is the requisite change to induce central apnea is referred to as the CO2 reserve, which can be positive or negative. CO2 reserve is defined as the difference between the eupneic end-tidal CO2 pressure and the end-tidal CO2 pressure induced by the ventilation protocol that is sufficient to trigger a central apnea as defined by the American Academy of Sleep Medicine. | one night | 
| Controller Gain | Controller gain is a ventilatory response to changes in end-tidal PCO2. Controller gain was calculated by dividing the difference in minute ventilation between the post-mechanical ventilation induced by the ventilation protocol and steady-state respiration by the difference in the end-tidal CO2 pressure between the mechanical ventilation and steady-state respiration. | one night | 
| Stead-State Plant Gain (mmHg | Plant gain is a blood gas response to a change in ventilation. This measure represents the effectiveness of the plant in eliminating CO2. Steady-state plant gain was calculated from the ratio of end-tidal CO2 to minute ventilation during stable respiration. | one night | 
| Respiratory Arousal Threshold | The nadir pressure in the upper airway (supra-glottic pressure) prior to the occurrence of an arousal | one night | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep-disordered Breathing, central sleep apnea