Metabolic Impact of Intermittent CPAP

Study Overview
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Brief Summary
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Obstructive sleep apnea is a risk factor for diabetes and cardiovascular disease, by unknown mechanisms. The investigators hypothesize that sleep apnea changes glucose and lipid metabolism during sleep, which over time could lead to diabetes and cardiovascular disease. This study examines metabolic changes during sleep in patients with obstructive sleep apnea. Patients accustomed to CPAP therapy are enrolled to undergo sleep studies, either on CPAP therapy or after withdrawing from CPAP for 3 nights. During sleep, blood samples are obtained so that metabolic function can be compared between sleep apnea and CPAP nights.

Detailed Description
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Participants with a history of moderate severe sleep apnea (AHI>20) will be enrolled if participants meet inclusion/exclusion criteria. Investigators will report to the sleep laboratory on two nights, (1) after continuing their CPAP or (2) after discontinuing CPAP for 3 nights. The order of observation will be randomized. A standard research dinner is provided before each study. IV's are placed so that blood can be sampled at frequent (30 min) intervals throughout the night. In the morning after each study, a glucose tolerance test and endothelial function study (endoPAT) are performed. Serum samples will be analyzed for glucose, insulin, free fatty acids, triglycerides, hormones, and other metabolic biomarkers.

Official Title
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Metabolic Impact of Intermittent CPAP

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Other: CPAP withdrawal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of moderate to severe Obstructive sleep apnea (OSA) (AHI or respiratory disturbance index (RDI)> 10). They must also own a CPAP machine and report the ability to tolerate sleeping with or without CPAP during the night. Exclusion Criteria: Uncontrolled hypertension with systolic blood pressure >170 or diastolic blood pressure > 110 Congestive heart failure Use of clonidine or nicotinic acid medication Diabetes requiring the use of insulin Known pregnancy, by urine testing in women of child-bearing age History of falling asleep while driving, near miss High risk occupation (pilot, commercial driver) Hemoglobin < 10 g/dL on point of care screening

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: CPAP (Usual care)<br>Continuation of established CPAP therapy. CPAP will be worn during a metabolic sleep study in the research laboratory. | |
| Experimental: CPAP withdrawal;<br>Cessation of established CPAP therapy for 3 nights. CPAP will NOT be worn during this period, and a metabolic sleep study off CPAP is performed in the research laboratory on the third night. | Other: CPAP withdrawal<br>* CPAP is discontinued for 3 nights.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of Free Fatty Acids (FFA, mmol/L) | Serial samples taken during sleep, 29 time points per night, 2 nights | 2 nights, <1 month apart, each visit with 29 time points | 
| Change in concentration of Glucose (mg/dl) | Serial samples taken during sleep, 29 time points per night, 2 nights | 2 nights, <1 month apart, each visit with 29 time points | 
| Change in concentration of Insulin (mcU/ml) | Serial samples taken during sleep, 29 time points per night, 2 nights | 2 nights, <1 month apart, each visit with 29 time points | 
| Change in concentration of Triglycerides (mg/dl) | Serial samples taken during sleep, 29 time points per night, 2 nights | 2 nights, <1 month apart, each visit with 29 time points | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serial Oral Glucose Tolerance Test (OGTT) to assess change over time | Serial samples taken in the morning after each sleep study, 5 time points | 2 nights, <1 month apart, each visit with 5 time points | 
| Change in Reactive hyperemia Index (RHI) | Measured in the morning using Itamar EndoPAT device. This will measure the ratio of blood flow after brachial artery occlusion to blood flow prior to brachial artery occlusion. Normal values range from approximately 1 to 3 with higher values being associated with better vascular function. | 2 nights, <1 month apart, 1 measurement each visit | 
| Change in Augmentation Index (AI) | Measured in the morning using Itamar EndoPAT device | 2 nights, <1 month apart, 1 measurement each visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obstructive sleep apnea, CPAP, metabolism