Obstructive Sleep Apnea, Polycystic Ovary Syndrome
Conditions
Keywords
PCOS, OSA, Metabolism, Diabetes
Brief summary
The purpose of this study is to look at the metabolic (use of energy) and hormonal features of sleep problems in women with polycystic ovary syndrome (PCOS).
Detailed description
The prevalence of obesity and chronic sleep loss are at record levels among Americans and evidence continues to emerge to support a causal link between the two conditions. Metabolic abnormalities related to sleep disruption are particularly evident in individuals with obstructive sleep apnea (OSA), a disorder traditionally associated with male gender. While more prevalent in men, OSA is underrecognized in women in part because its clinical and polysomnographic features differ from those of men. Women with polycystic ovary syndrome (PCOS) are particularly susceptible to OSA with at least a 5-fold higher risk for its development compared to obese women without PCOS. This study will enroll obese women with PCOS, with and without OSA. Those with OSA will be randomized to receive CPAP or to receive depot leuprolide to suppress ovarian steroid output over 12 weeks, reassessed at 6 weeks, and then randomized (double-blind, placebo controlled) to 6 weeks of either micronized estrogen + placebo or micronized progestin + placebo. The independent effects of androgen, estrogen, and progesterone on OSA and metabolic function will be assessed. In addition, primary human adipocytes will be prepared from fat biopsies obtained from subjects. Insulin sensitivity will be determined by phospho-specific immunoblotting in conjunction with glucose uptake and anti-lipolysis assays. In parallel, adipocytes from these subjects will be cultured for 1-5 days prior to metabolic assays to ascertain if removal of from circulating factors will improve insulin signaling, or if insulin resistance persists in vitro. Finally, there will be an interface with the Metabolomics Laboratory at Duke University (C. Newgard, Lab Director), and metabolomics assessment will be done on blood and urine samples.
Interventions
DRUGDepot Lupron followed by estrogen plus placebo
A single intramuscular dose of depot lupron (11.25 mg). Six weeks after injection, subjects will receive daily oral doses of estrogen (2mg) plus placebo for six weeks.
Sponsors
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of PCOS * Obese (BMI of at least 30 kg/m2)
Exclusion criteria
* Diagnosis of nonclassic 21-hydroxylase deficiency, Cushing syndrome, hypothyroidism, or significant elevations in prolactin * Taking steroid preparations (including oral contraceptives), medications known to alter insulin secretion and/or action, or medications known to influence sleep during the 2 months prior to starting the study * Positive pregnancy test * Diagnosis of diabetes mellitus * Hypertension (systolic \> 140 mmHg and/or diastolic \> 90 mmhg) not well-controlled on stable medication with either ACE inhibitors or diuretics * Habitual alcohol use * Excessive caffeine intake of more than 300 mg/day * Known peanut allergies, or allergies to medications used in the study * Hemoglobin \< 11g/dL and/or hematocrit \< 33% * Systemic illnesses, including heart, renal, liver, or malignant disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estrogen Levels | Baseline | Estrogen levels measured every 20 minutes for 24 hours and the the average of those values are presented. The units of measurement are picograms per milliter (pg/ml). |
| Sleep Efficiency Measured at Baseline | Baseline | Sleep efficiency recorded with polysomnography minimum value = 0%, maximum value = 100%, higher values are a better outcome. |
| Total Testosterone | Baseline | Total Testosterone levels measured every 20 minutes for 24 hours and the average of those values are presented. The units of measurement are picograms per milliter (pg/ml). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intravenous Glucose Tolerance Test | Baseline | Acute Insulin Response measured by the intravenous glucose tolerance test measured during baseline. The unit of measurement is mg/dl. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Specific Aim 1 Baseline analysis comparing PCOS women with OSA to PCOS women without OSA. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Specific Aim 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 26.7 years STANDARD_DEVIATION 5.5 |
| Race/Ethnicity, Customized African American | 8 Participants |
| Race/Ethnicity, Customized Caucasian | 9 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 0 | 0 / 1 |
| other Total, other adverse events | 0 / 18 | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 18 | 0 / 0 | 0 / 1 |
Outcome results
Primary
Estrogen Levels
Estrogen levels measured every 20 minutes for 24 hours and the the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).
Time frame: Baseline
Population: The number of patients in Specific Aim 2 is zero, since the one patient randomized to Lupron dropped out.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Specific Aim 1: Women Without Obstructive Sleep Apnea | Estrogen Levels | 73.3 pg/ml | Standard Deviation 32.5 |
| Specific Aim 1: Women With Obstructive Sleep Apnea | Estrogen Levels | 69.9 pg/ml | Standard Deviation 14.1 |
| Specific Aim 3 | Estrogen Levels | 61.0 pg/ml | Standard Deviation 18.2 |
Primary
Sleep Efficiency Measured at Baseline
Sleep efficiency recorded with polysomnography minimum value = 0%, maximum value = 100%, higher values are a better outcome.
Time frame: Baseline
Population: Patients dropped out after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Specific Aim 1: Women Without Obstructive Sleep Apnea | Sleep Efficiency Measured at Baseline | 93.2 Percentage | Standard Deviation 4 |
| Specific Aim 1: Women With Obstructive Sleep Apnea | Sleep Efficiency Measured at Baseline | 86.7 Percentage | Standard Deviation 7 |
| Specific Aim 3 | Sleep Efficiency Measured at Baseline | 92.3 Percentage | — |
Primary
Total Testosterone
Total Testosterone levels measured every 20 minutes for 24 hours and the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).
Time frame: Baseline
Population: patients dropped out after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Specific Aim 1: Women Without Obstructive Sleep Apnea | Total Testosterone | 70.5 pg/ml | Standard Deviation 44.7 |
| Specific Aim 1: Women With Obstructive Sleep Apnea | Total Testosterone | 50.9 pg/ml | Standard Deviation 26.4 |
| Specific Aim 3 | Total Testosterone | 45.3 pg/ml | Standard Deviation 14.8 |
Secondary
Intravenous Glucose Tolerance Test
Acute Insulin Response measured by the intravenous glucose tolerance test measured during baseline. The unit of measurement is mg/dl.
Time frame: Baseline
Population: Patients dropped out after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Specific Aim 1: Women Without Obstructive Sleep Apnea | Intravenous Glucose Tolerance Test | 938.5 mg/dl | Standard Deviation 770.1 |
| Specific Aim 1: Women With Obstructive Sleep Apnea | Intravenous Glucose Tolerance Test | 730.6 mg/dl | Standard Deviation 478.1 |
| Specific Aim 3 | Intravenous Glucose Tolerance Test | 189.5 mg/dl | — |