Metabolic Study of Women With Polycystic Ovary Syndrome and Sleep Apnea

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified July 2024 by University of Chicago
Sponsor
University of Chicago
Information Provided by (Responsible Party)
University of Chicago
Clinicaltrials.gov Identifier
NCT00696111
Other Study ID Numbers:
15872B
First Submitted
June 8, 2008
First Posted
June 11, 2008
Results First Posted
June 29, 2023
Last Update Posted
December 30, 2024
Last Verified
July 2024

ClinicalTrials.gov processed this data on December 2024Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Polycystic Ovary SyndromeObstructive Sleep Apnea
Drug: Depot Lupron followed by estrogen plus placebo

Study Design

Study TypeInterventional
Actual Enrollment18 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitlePCOS, Sleep Apnea and Metabolic Risk in Women
Study Start DateNovember 30, 2007
Actual Primary Completion DateJune 29, 2022
Actual Study Completion DateJune 29, 2022

Groups and Cohorts

Group/CohortIntervention/Treatment
Depot Lupron and estrogen plus placebo
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.

Outcome Measures

Primary Outcome Measures
  1. Estrogen Levels
    Estrogen levels measured every 20 minutes for 24 hours and the the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).
  2. Sleep Efficiency Measured at Baseline
    Sleep efficiency recorded with polysomnography minimum value = 0%, maximum value = 100%, higher values are a better outcome.
  3. Total Testosterone
    Total Testosterone levels measured every 20 minutes for 24 hours and the average of those values are presented. The units of measurement are picograms per milliter (pg/ml).
Secondary Outcome Measures
  1. Intravenous Glucose Tolerance Test
    Acute Insulin Response measured by the intravenous glucose tolerance test measured during baseline. The unit of measurement is mg/dl.

Eligibility Criteria

Ages Eligible for Study(Adult)
Sexes Eligible for StudyFemale
Accepts Healthy VolunteersNo
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

Sponsors and CollaboratorsUniversity of Chicago
Locations
University of Chicago Department of Medicine, Section of Endocrinology, Diabetes & Metabolism | Chicago Illinois, United States, 60637
Investigators
Principal Investigator: David A Ehrmann, MD, University of Chicago
Study Documents (Full Text)
Documents provided by University of ChicagoStudy Protocol and Statistical Analysis Plan  June 14, 2023