Metabolism and Sleep Apnea Treatment

Study Overview
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Brief Summary
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The purpose of this research study is to see if obstructive sleep apnea (OSA) is associated with abnormalities in fat metabolism. Through this research study, the Investigator will evaluate how fat is metabolized in people with and without sleep apnea, what substances the fat tissue releases, and how these substances might change the way the body uses energy and sugar.

Official Title
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Metabolism and Sleep Apnea Treatment

Conditions
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Obstructive Sleep Apnea, Fat Disorder

Intervention / Treatment
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* Device: PAP Therapy
* Behavioral: Lifestyle Counseling Intervention


Participation Criteria
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Eligibility Criteria
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Aim 1 Group: Inclusion criteria: Age between 18-70 years Ability to provide consent Exclusion criteria Body Mass Index (BMI) > 40 kg/m2 Prevalent myocardial infarction, coronary revascularization, heart failure, and stroke Type 1 or Type 2 diabetes mellitus Current or prior use of PAP or oral appliance therapy for OSA Use of oral corticosteroids Unstable medical conditions that may preclude enrollment in the protocol such as: uncontrolled angina and/or congestive heart failure, uncontrolled blood pressure or resistant hypertension, severe chronic obstructive pulmonary disease, cancer, and active psychiatric disease (e.g., major depression) Other sleep disorders (e.g., circadian rhythm disorder, self-reported habitual sleep duration < 6h) Use of supplemental oxygen during wakefulness or sleep Central sleep apnea, obesity hypoventilation syndrome or Cheyne-Stokes respiration based on the home sleep test Resting awake Oxygen Saturation (SpO2) < 90% Aim 2 Group: Inclusion criteria: Age between 18-70 years Ability to provide consent Moderate-to-severe OSA (AHI ≥ 15/h); Demonstration of Positive Airway Pressure (PAP) use of > 4 h/night on 70% of the nights during 1-week run-in period Successful completion of all of the procedures for Aim 1. Exclusion criteria: BMI: ≥ 40 kg/m2 Type 1 or Type 2 diabetes mellitus Current use of PAP or oral appliance therapy for OSA Commercial driver or report of motor vehicle accident or near-miss due to sleepiness within the 2 previous years Epworth sleepiness score of 18 or more Use of oral corticosteroids Participation in another clinical trial Unstable medical conditions that may preclude enrollment in the protocol such as: uncontrolled angina and/or congestive heart failure, uncontrolled blood pressure or resistant hypertension, severe chronic obstructive pulmonary disease, cancer, and active psychiatric disease (e.g., major depression) Other sleep disorders (e.g., circadian rhythm disorder, self-reported habitual sleep duration < 6h) Use of supplemental oxygen during wakefulness or sleep Central sleep apnea, obesity hypoventilation syndrome or Cheyne-Stokes respiration based on the home sleep test Resting awake SpO2 < 90%

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No Intervention (Aim 1) Group<br>Participants in this group will not receive an intervention and will only undergo several testing procedures conducted within 3 to 4 weeks to assess OSA severity. | |
| Experimental: PAP Therapy and Lifestyle Intervention (Aim 2) Group<br>Participants in the Aim 1 Group found to have moderate to severe OSA (defined as having a Apnea-Hypopnea Index (AHI) of 15.0 events/hour or more) randomized to this arm will receive the PAP therapy and Lifestyle Intervention for 12 weeks. | Device: PAP Therapy<br>* Auto-PAP device (ResMed AirsenseTM Autoset) with a heated humidifier will be provided along with an appropriate mask and connecting hose for nightly use<br>Behavioral: Lifestyle Counseling Intervention<br>* Lifestyle intervention will include counseling on (a) education on nutrition and exercise; and (b) behavioral support for identifying lifestyle change strategies and problem-solving barriers to improve the regularity and duration of sleep. This will be conducted using brochures on weight loss and sleep hygiene<br>|
| Experimental: Lifestyle Intervention Only (Aim 2) Group<br>Participants in the Aim 1 Group found to have moderate to severe OSA (defined as having a Apnea-Hypopnea Index (AHI) of 15.0 events/hour or more) randomized to this arm will receive only the Lifestyle Intervention for 12 weeks. | Behavioral: Lifestyle Counseling Intervention<br>* Lifestyle intervention will include counseling on (a) education on nutrition and exercise; and (b) behavioral support for identifying lifestyle change strategies and problem-solving barriers to improve the regularity and duration of sleep. This will be conducted using brochures on weight loss and sleep hygiene<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole body lipolysis rate | Measured using the Intravenous Glucose Tolerance Test (IVGTT) in micromoles/L/min assessed at baseline and again at 3 months | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free Fatty Acids (FFA) Oxidation Rate | Measured using the IVGTT in micromoles/L/min assessed at baseline and again at 3 months | Up to 3 months | 
| Adipocyte insulin resistance | Measured using the IVGTT in micromoles-microunits/L-ml assessed at baseline and again at 3 months | Up to 3 months | 
| Lipolysis suppression slope | Measured using the IVGTT in micromoles/L-min assessed at baseline and again at 3 months | Up to 3 months | 
| Free fatty acid rebound slope | Measured using the IVGTT in micromoles/L-min assessed at baseline and again at 3 months | Up to 3 months | 
| Free fatty acid insulin sensitivity parameter | Measured using the IVGTT in (picomoles/L x min)^-1 assessed at baseline and again at 3 months | Up to 3 months | 
| Insulin sensitivity | Measured using the IVGTT in (milliunits/L x min)^-1 assessed at baseline and again at 3 months | Up to 3 months | 
| Acute insulin response to glucose | Measured using the IVGTT in (milliunits/L) x minute assessed at baseline and again at 3 months | Up to 3 months | 
| Glucose effectiveness | Measured using the IVGTT in per minute assessed at baseline and again at 3 months | Up to 3 months |