Clinical trial NCT00696111: Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea
Official title: PCOS, Sleep Apnea and Metabolic Risk in Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Obstructive Sleep Apnea
Keywords: PCOS
OSA
Metabolism
Diabetes
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Duke University
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2008-06-12
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Estrogen Levels
timeFrame: Baseline
measure: Sleep Efficiency Measured at Baseline
timeFrame: Baseline
measure: Total Testosterone
timeFrame: Baseline
Secondary outcomes:
measure: Intravenous Glucose Tolerance Test
timeFrame: Baseline
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism
state: Illinois
Study officials:
affiliation: University of Chicago
name: David A Ehrmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hoffman LK, Ehrmann DA. Cardiometabolic features of polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2008 Apr;4(4):215-22. doi: 10.1038/ncpendmet0755. Epub 2008 Feb 5.
citation: Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1044-9. doi: 10.1073/pnas.0706446105. Epub 2008 Jan 2.
citation: Dronavalli S, Ehrmann DA. Pharmacologic therapy of polycystic ovary syndrome. Clin Obstet Gynecol. 2007 Mar;50(1):244-54. doi: 10.1097/GRF.0b013e31802f35a0.
citation: Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN; PCOS/Troglitazone Study Group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Jan;91(1):48-53. doi: 10.1210/jc.2005-1329. Epub 2005 Oct 25.
citation: Tasali E, Van Cauter E, Ehrmann DA. Relationships between sleep disordered breathing and glucose metabolism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Jan;91(1):36-42. doi: 10.1210/jc.2005-1084. Epub 2005 Oct 11.
citation: Tasali E, Chapotot F, Leproult R, Whitmore H, Ehrmann DA. Treatment of obstructive sleep apnea improves cardiometabolic function in young obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011 Feb;96(2):365-74. doi: 10.1210/jc.2010-1187. Epub 2010 Dec 1.