Clinical trial NCT00706511: Metabolic Study of Sleep Apnea in Men and Women
Official title: Sleep and Metabolism in Obesity: Impact of Gender
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea (OSA)
Keywords: OSA
Diabetes
Metabolism
Gender
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: 2008-06-27
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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 men and women.

Detailed description: Obesity is a major risk factor for obstructive sleep apnea (OSA), a condition characterized by repetitive respiratory disturbances, intermittent hypoxia, sleep fragmentation by frequent microarousals and low amounts of deep slow wave sleep (SWS). Today, more than 10 million American women suffer from OSA. OSA has been identified as an independent risk factor for the metabolic syndrome. Because OSA is more prevalent in men than in women, a disproportionate number of studies of OSA and its consequences have been conducted in men. Thus, OSA has been characterized as a disorder associated with gender-based health care inequity. Recent evidence, including data from our group, suggests that reduced amounts and intensity of SWS (i.e. slow-wave activity \[SWA\]) may play a pivotal role in the development of metabolic and cardiovascular disturbances in obese men and women, particularly those with OSA. This project will focus on sex differences in SWA and their relationship with daytime sleepiness and metabolic vulnerability in obese men and women with and without OSA. We propose to simultaneously characterize: 1. sleep-wake regulation; 2. measures of diabetes risk; 3. measures of cardiovascular risk; and 4. profiles of sex steroids, cortisol and adipokines in a. obese men without OSA, b. obese men with OSA before and after treatment with continuous positive airway pressure (CPAP), c. obese pre-menopausal women without OSA, and d. obese pre-menopausal women with OSA before and after CPAP treatment. The completion of these interdisciplinary studies will provide a unique data set contrasting in obese women versus obese men the relationships between sleep and the metabolic syndrome, OSA and the metabolic syndrome and the impact of CPAP treatment on the metabolic syndrome. This work will provide important insights regarding the pathophysiology of OSA and its adverse consequences in obese men and women, and the basis for the development of effective sex-specific prevention and treatment strategies.

Eligibility criteria: Inclusion Criteria:

* Obese (BMI of at least 30 kg/m2)

Exclusion Criteria:

* Clinically significant depression
* 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
* Hemoglobin \< 11g/dL and/or hematocrit \< 33%
* Systemic illnesses, including heart, renal, liver, or malignant disease
* 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
* Travel across time zones during the 4 weeks prior to starting the study
* Irregular sleeping habits (including shift work)

Primary outcomes:
measure: Polysomnography - Apnea-hypopnea Index (AHI)
timeFrame: After 6 weeks of CPAP (Treatment)
measure: Polysomnography - Minutes of N3 Stage
timeFrame: After 6 weeks of CPAP (Treatment)
measure: Polysomnography - Minutes of REM Stage
timeFrame: After 6 weeks of CPAP (Treatment)
measure: Polysomnography - Sleep Efficiency
timeFrame: After 6 weeks of CPAP (Treatment)
Secondary outcomes:
measure: IVGTT (Intravenous Tolerance Test) - Sensitivity Index (SI)
timeFrame: After treatment (6 weeks)
measure: IVGTT (Intravenous Tolerance Test) - Acute Insulin Response
timeFrame: After treatment (6 weeks)
measure: IVGTT (Intravenous Tolerance Test) - Disposition Index (DI)
timeFrame: After treatment (6 weeks)
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: Eve Van Cauter, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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, Mokhlesi B, Van Cauter E. Obstructive sleep apnea and type 2 diabetes: interacting epidemics. Chest. 2008 Feb;133(2):496-506. doi: 10.1378/chest.07-0828.
citation: Knutson KL, Spiegel K, Penev P, Van Cauter E. The metabolic consequences of sleep deprivation. Sleep Med Rev. 2007 Jun;11(3):163-78. doi: 10.1016/j.smrv.2007.01.002. Epub 2007 Apr 17.
citation: Van Cauter E, Holmback U, Knutson K, Leproult R, Miller A, Nedeltcheva A, Pannain S, Penev P, Tasali E, Spiegel K. Impact of sleep and sleep loss on neuroendocrine and metabolic function. Horm Res. 2007;67 Suppl 1:2-9. doi: 10.1159/000097543. Epub 2007 Feb 15.
citation: Knutson KL, Ryden AM, Mander BA, Van Cauter E. Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus. Arch Intern Med. 2006 Sep 18;166(16):1768-74. doi: 10.1001/archinte.166.16.1768.
citation: Latta F, Leproult R, Tasali E, Hofmann E, L'Hermite-Baleriaux M, Copinschi G, Van Cauter E. Sex differences in nocturnal growth hormone and prolactin secretion in healthy older adults: relationships with sleep EEG variables. Sleep. 2005 Dec;28(12):1519-24. doi: 10.1093/sleep/28.12.1519.