Obstructive Sleep Apnea
Conditions
Keywords
obstructive sleep apnea, CPAP, metabolism
Brief summary
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 continuous positive airway pressure (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
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.
Interventions
OTHERCPAP withdrawal
CPAP is discontinued for 3 nights.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
American Academy of Sleep Medicine
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Plasma Free Fatty Acids (FFA, mmol/L) | 2 nights, <1 month apart. Data from each night was averaged to report a single value. | We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
| Concentration of Plasma Glucose (mg/dl) | 2 nights, <1 month apart. Data from each night was averaged to report a single value. | We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
| Concentration of Plasma Insulin (mcU/ml) | 2 nights, <1 month apart. Data from each night was averaged to report a single value. | We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
| Concentration of Plasma Triglycerides (mg/dl) | 2 nights, <1 month apart. Data from each night was averaged to report a single value. | We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reactive Hyperemia Index (RHI) | 2 nights, <1 month apart, 1 measurement each visit | 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. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
| Augmentation Index (AI) | 2 nights, <1 month apart, 1 measurement each visit | Measured in the morning using Itamar EndoPAT device. Augmentation index is measured once during each visit, and is expressed as a % increase in the pressure waveform during systole. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal). |
| Oral Glucose Tolerance Test (OGTT) | 2 nights, <1 month apart. 5 OGTT values were averaged to a obtain a single value. | We will report the mean of the area under the curve (AUC) during OGTT for all participants per group (CPAP vs. CPAP withdrawal). |
Countries
United States
Participant flow
Recruitment details
Patients with a history of obstructive sleep apnea (OSA) who were accustomed to CPAP use were enrolled from the Johns Hopkins Sleep Disorders Center.
Pre-assignment details
144 participants signed a consent form. 15 subjects withdrew or were lost to follow up after consent, leaving 129 participants who were randomized to CPAP first (61) or CPAP withdrawal first (68) visits.
Participants by arm
| Arm | Count |
|---|---|
| CPAP First, Then OSA (CPAP Withdrawal) This is a crossover study comparing effects of sleep apnea (CPAP withdrawal) vs CPAP.
Participants in this arm undergo a (1) CPAP study (continuation of established CPAP therapy), followed by a (2) CPAP withdrawal study. | 61 |
| OSA First (CPAP Withdrawal), Then CPAP This is a crossover study comparing effects of sleep apnea (CPAP withdrawal) vs CPAP.
Participants in this arm undergo a (1) CPAP withdrawal study, followed by a (2) CPAP study (continuation of established CPAP therapy). | 68 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention (1 Night) | Withdrawal by Subject | 4 | 3 |
| Washout (1 to 4 Weeks) | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Total | OSA First (CPAP Withdrawal), Then CPAP | CPAP First, Then OSA (CPAP Withdrawal) |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 12 | 53 years STANDARD_DEVIATION 12 | 51 years STANDARD_DEVIATION 12 |
| Diabetes status Diabetes | 42 Participants | 23 Participants | 19 Participants |
| Diabetes status No diabetes | 59 Participants | 34 Participants | 25 Participants |
| Diabetes status Prediabetes | 28 Participants | 11 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 65 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| History of hypertension Hypertension | 62 Participants | 31 Participants | 31 Participants |
| History of hypertension No hypertension | 67 Participants | 37 Participants | 30 Participants |
| Race/Ethnicity, Customized Race African American | 38 Participants | 17 Participants | 21 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Caucasian | 79 Participants | 44 Participants | 35 Participants |
| Race/Ethnicity, Customized Race Mixed | 5 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Native American | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 129 Participants | 68 Participants | 61 Participants |
| Sex: Female, Male Female | 47 Participants | 26 Participants | 21 Participants |
| Sex: Female, Male Male | 82 Participants | 42 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 129 |
| other Total, other adverse events | 2 / 129 | 0 / 129 |
| serious Total, serious adverse events | 0 / 129 | 0 / 129 |
Outcome results
Primary
Concentration of Plasma Free Fatty Acids (FFA, mmol/L)
We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart. Data from each night was averaged to report a single value.
Population: missing values due to IV issues leading to incomplete collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Concentration of Plasma Free Fatty Acids (FFA, mmol/L) | 0.47 mmol/L | Standard Deviation 14 |
| CPAP Withdrawal | Concentration of Plasma Free Fatty Acids (FFA, mmol/L) | 0.51 mmol/L | Standard Deviation 0.12 |
Primary
Concentration of Plasma Glucose (mg/dl)
We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart. Data from each night was averaged to report a single value.
Population: missing values due to IV issues leading to incomplete collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Concentration of Plasma Glucose (mg/dl) | 100 mg/dl | Standard Deviation 18 |
| CPAP Withdrawal | Concentration of Plasma Glucose (mg/dl) | 101 mg/dl | Standard Deviation 21 |
Primary
Concentration of Plasma Insulin (mcU/ml)
We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart. Data from each night was averaged to report a single value.
Population: missing values due to IV issues leading to incomplete collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Concentration of Plasma Insulin (mcU/ml) | 18 microunits/mL | Standard Deviation 8 |
| CPAP Withdrawal | Concentration of Plasma Insulin (mcU/ml) | 18 microunits/mL | Standard Deviation 12 |
Primary
Concentration of Plasma Triglycerides (mg/dl)
We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart. Data from each night was averaged to report a single value.
Population: Missing values due to IV issues leading to incomplete collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Concentration of Plasma Triglycerides (mg/dl) | 127 mg/dl | Standard Deviation 65 |
| CPAP Withdrawal | Concentration of Plasma Triglycerides (mg/dl) | 128 mg/dl | Standard Deviation 74 |
Secondary
Augmentation Index (AI)
Measured in the morning using Itamar EndoPAT device. Augmentation index is measured once during each visit, and is expressed as a % increase in the pressure waveform during systole. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart, 1 measurement each visit
Population: Some missing data due to technical problems during collection of EndoPAT data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Augmentation Index (AI) | 3.3 percentage | Standard Deviation 16 |
| CPAP Withdrawal | Augmentation Index (AI) | 6.3 percentage | Standard Deviation 16 |
Secondary
Oral Glucose Tolerance Test (OGTT)
We will report the mean of the area under the curve (AUC) during OGTT for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart. 5 OGTT values were averaged to a obtain a single value.
Population: Missing values due to IV issues leading to incomplete collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Oral Glucose Tolerance Test (OGTT) | 19820 mg/dl*min | Standard Deviation 5818 |
| CPAP Withdrawal | Oral Glucose Tolerance Test (OGTT) | 19224 mg/dl*min | Standard Deviation 5324 |
Secondary
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. We will report the mean for all participants per group (CPAP vs. CPAP withdrawal).
Time frame: 2 nights, <1 month apart, 1 measurement each visit
Population: Some missing data due to technical problems during collection of EndoPAT data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Reactive Hyperemia Index (RHI) | 2.21 Ratio | Standard Deviation 0.57 |
| CPAP Withdrawal | Reactive Hyperemia Index (RHI) | 2.12 Ratio | Standard Deviation 0.65 |