Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

Official title:

PCOS, Sleep Apnea and Metabolic Risk in Women

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00696111
• Other study ID #: 15872B
• Secondary ID: 1P50HD057796
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 2007
• Est. completion date: June 2023

Study information

• Verified date: May 2023
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: June 2023
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Polycystic Ovary Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
University of Chicago	Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Dronavalli S, Ehrmann DA. Pharmacologic therapy of polycystic ovary syndrome. Clin Obstet Gynecol. 2007 Mar;50(1):244-54. doi: 10.1097/GRF.0b013e31802f35a0. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sex steroid levels		After treatment (6 weeks)
Primary	Sleep recording/polysomnography		After treatment (6 weeks)
Secondary	Frequently sampled IVGTT		After treatment (6 weeks)
Secondary	24-hour hormonal profiles		After treatment (6 weeks)

External Links

•   University of Chicago Center for Polycystic Ovary Syndrome