Official Title: “PCOS, Sleep Apnea and Metabolic Risk in Women”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Factorial Assignment, Efficacy Study

Study Primary Completion Date: August 2012

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.

Intervention(s) in this Clinical Trial

• Drug: Depot 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.
• Drug: Depot Lupron followed by progesterone plus placebo.
  • 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.
• Device: CPAP
  • CPAP (continuous positive airway pressure) treatment at home for six weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1A
  • Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive estrogen plus placebo for another 6 weeks.
• Experimental: 1B
  • Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive progesterone plus placebo for another 6 weeks.
• Experimental: 3
  • Randomized to receive CPAP (continuous positive airway pressure) treatment for 6 weeks.

Primary Measures

• Sex steroid levels
  • Time Frame: After treatment (6 weeks)
    Safety Issue?: No
• Sleep recording/polysomnography
  • Time Frame: After treatment (6 weeks)
    Safety Issue?: No

Secondary Measures

• Frequently sampled IVGTT
  • Time Frame: After treatment (6 weeks)
    Safety Issue?: No
• 24-hour hormonal profiles
  • Time Frame: After treatment (6 weeks)
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Chicago

Overall Clinical Trial Officials and Contacts

David A Ehrmann, MD Principal Investigator University of Chicago  

Overall Contact: Abeer Rue 773-702-4295 ahaddad@medicine.bsd.uchicago.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00696111

Study ID Number: 15872B

ClinicalTrials.gov Identifier: NCT00696111

Health Authority: United States: Food and Drug Administration

University of Chicago Center for Polycystic Ovary Syndrome