Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea
Primary Purpose
Polycystic Ovary Syndrome, Obstructive Sleep Apnea
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Depot Lupron followed by estrogen plus placebo
Depot Lupron followed by progesterone plus placebo.
CPAP
Sponsored by
About this trial
This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring PCOS, OSA, Metabolism, Diabetes
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
Sites / Locations
- University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
1A
1B
3
Arm Description
Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive estrogen plus placebo for another 6 weeks.
Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive progesterone plus placebo for another 6 weeks.
Randomized to receive CPAP (continuous positive airway pressure) treatment for 6 weeks.
Outcomes
Primary Outcome Measures
Sex steroid levels
Sleep recording/polysomnography
Secondary Outcome Measures
Frequently sampled IVGTT
24-hour hormonal profiles
Full Information
NCT ID
NCT00696111
First Posted
June 9, 2008
Last Updated
May 25, 2023
Sponsor
University of Chicago
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT00696111
Brief Title
Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea
Official Title
PCOS, Sleep Apnea and Metabolic Risk in Women
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2007 (undefined)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
June 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, Obstructive Sleep Apnea
Keywords
PCOS, OSA, Metabolism, Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1A
Arm Type
Experimental
Arm Description
Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive estrogen plus placebo for another 6 weeks.
Arm Title
1B
Arm Type
Experimental
Arm Description
Randomized to receive depot Lupron for 6 weeks. Then randomized again to receive progesterone plus placebo for another 6 weeks.
Arm Title
3
Arm Type
Experimental
Arm Description
Randomized to receive CPAP (continuous positive airway pressure) treatment for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Depot Lupron followed by estrogen plus placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Depot Lupron followed by progesterone plus placebo.
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
CPAP
Intervention Description
CPAP (continuous positive airway pressure) treatment at home for six weeks.
Primary Outcome Measure Information:
Title
Sex steroid levels
Time Frame
After treatment (6 weeks)
Title
Sleep recording/polysomnography
Time Frame
After treatment (6 weeks)
Secondary Outcome Measure Information:
Title
Frequently sampled IVGTT
Time Frame
After treatment (6 weeks)
Title
24-hour hormonal profiles
Time Frame
After treatment (6 weeks)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A Ehrmann, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18250636
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.
Results Reference
background
PubMed Identifier
18172212
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.
Results Reference
background
PubMed Identifier
17304039
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.
Results Reference
background
PubMed Identifier
16249284
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.
Results Reference
background
PubMed Identifier
16219719
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.
Results Reference
background
PubMed Identifier
21123449
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.
Results Reference
derived
Links:
URL
http://www.uchospitals.edu/specialties/pcos/
Description
University of Chicago Center for Polycystic Ovary Syndrome
Learn more about this trial
Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea
We'll reach out to this number within 24 hrs