Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea - Full Text View

Purpose

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).

Condition	Intervention
Polycystic Ovary Syndrome Obstructive Sleep Apnea	Drug: Depot Lupron followed by estrogen plus placebo Drug: Depot Lupron followed by progesterone plus placebo. Device: CPAP


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	PCOS, Sleep Apnea and Metabolic Risk in Women

Resource links provided by NLM:

MedlinePlus related topics: Polycystic Ovary Syndrome Sleep Apnea

Drug Information available for: Progesterone Leuprolide acetate

U.S. FDA Resources

Further study details as provided by University of Chicago:

Primary Outcome Measures:

Sex steroid levels [ Time Frame: After treatment (6 weeks) ] [ Designated as safety issue: No ]
Sleep recording/polysomnography [ Time Frame: After treatment (6 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Frequently sampled IVGTT [ Time Frame: After treatment (6 weeks) ] [ Designated as safety issue: No ]
24-hour hormonal profiles [ Time Frame: After treatment (6 weeks) ] [ Designated as safety issue: No ]


Estimated Enrollment:	80
Study Start Date:	December 2007
Estimated Study Completion Date:	August 2017
Estimated Primary Completion Date:	August 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1A 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 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.
Experimental: 1B 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. 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.
Experimental: 3 Randomized to receive CPAP (continuous positive airway pressure) treatment for 6 weeks.	Device: CPAP CPAP (continuous positive airway pressure) treatment at home for six weeks.

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


Ages Eligible for Study:	18 Years to 40 Years (Adult)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696111

Locations


United States, Illinois
University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism
Chicago, Illinois, United States, 60637

Sponsors and Collaborators

University of Chicago

Duke University

Investigators


Principal Investigator:	David A Ehrmann, MD	University of Chicago

More Information

Additional Information:

University of Chicago Center for Polycystic Ovary Syndrome This link exits the ClinicalTrials.gov site

Publications:

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. Review.

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.

Dronavalli S, Ehrmann DA. Pharmacologic therapy of polycystic ovary syndrome. Clin Obstet Gynecol. 2007 Mar;50(1):244-54.

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. Epub 2005 Oct 25.

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. Epub 2005 Oct 11.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	University of Chicago
ClinicalTrials.gov Identifier:	NCT00696111 History of Changes
Other Study ID Numbers:	15872B 1P50HD057796
Study First Received:	June 9, 2008
Last Updated:	August 23, 2016
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of Chicago:


PCOS OSA Metabolism Diabetes

Additional relevant MeSH terms:


Syndrome Apnea Sleep Apnea Syndromes Sleep Apnea, Obstructive Polycystic Ovary Syndrome Disease Pathologic Processes Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Signs and Symptoms Sleep Disorders, Intrinsic Dyssomnias Sleep Wake Disorders Nervous System Diseases	Ovarian Cysts Cysts Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Gonadal Disorders Endocrine System Diseases Estrogens Progesterone Leuprolide Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Progestins

ClinicalTrials.gov processed this record on September 23, 2016