Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea

Study Overview
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Brief Summary
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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
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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.

Official Title
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PCOS, Sleep Apnea and Metabolic Risk in Women

Conditions
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Polycystic Ovary Syndrome, Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: Depot Lupron followed by estrogen plus placebo
* Drug: Depot Lupron followed by progesterone plus placebo.
* Device: CPAP


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A<br>Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive estrogen plus placebo for another 6 weeks. | Drug: Depot Lupron followed by estrogen plus placebo<br>* 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.<br>|
| Experimental: 1B<br>Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive progesterone plus placebo for another 6 weeks. | Drug: Depot Lupron followed by progesterone plus placebo.<br>* A single intramuscular dose of depot lupron (11.25 mg). Six weeks after injection, subjects will receive daily oral doses of progesterone (200mg) plus placebo for six weeks.<br>|
| Experimental: 3<br>Randomized to receive CPAP (continuous positive airway pressure) treatment for 6 weeks. | Device: CPAP<br>* CPAP (continuous positive airway pressure) treatment at home for six weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sex steroid levels |  | After treatment (6 weeks) | 
| Sleep recording/polysomnography |  | After treatment (6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequently sampled IVGTT |  | After treatment (6 weeks) | 
| 24-hour hormonal profiles |  | After treatment (6 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, OSA, Metabolism, Diabetes