Metabolic Study of Sleep Apnea in Men and Women

Sleep and Metabolism in Obesity: Impact of Gender

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00706511

Enrollment

Registered

2008-06-27

Start date

2007-12-31

Completion date

2012-08-22

Last updated

2020-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnea (OSA)

Keywords

OSA, Diabetes, Metabolism, Gender

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.

Interventions

DEVICECPAP

CPAP (continuous positive airway pressure) treatment at home for 6 weeks

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 40 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Polysomnography - Apnea-hypopnea Index (AHI)	After 6 weeks of CPAP (Treatment)	apnea-hypopnea index: number of apneas and hypopneas per hour of recording; a measure of the severity of obstructive sleep apnea; varies from min=0 to max=120; AHI between 0 and \<5: no significant sleep apnea; AHI between 5 and \<15: mild sleep apnea; AHI between 15 and \<30: moderate sleep apnea; AHI of 30 and above: severe sleep apnea.
Polysomnography - Minutes of N3 Stage	After 6 weeks of CPAP (Treatment)	Stage N3, sometimes referred to as delta sleep or slow wave sleep, is characterized by slow waves in the electro-encephalogram (EEG) that reflect synchronization of firing of cortical neurons. N3 sleep is considered the most restorative stage of sleep for both the brain and the rest of the body.
Polysomnography - Minutes of REM Stage	After 6 weeks of CPAP (Treatment)	—
Polysomnography - Sleep Efficiency	After 6 weeks of CPAP (Treatment)	Sleep efficiency: a measure of objective sleep quality; calculated from the polygraphic sleep recording as the ratio of time spent asleep during the scheduled sleep period to total scheduled sleep period. Expressed in %. Varies from 0% (the subject did not sleep at all) to 100% (the subject spent the entire scheduled sleep period asleep).

Secondary

Measure	Time frame	Description
IVGTT (Intravenous Tolerance Test) - Acute Insulin Response	After treatment (6 weeks)	Acute Insulin Response is calculated as the area under the insulin curve for the first 19 minutes after intravenous glucose injection. Area under the insulin curve is expressed in pmol x min/L.
IVGTT (Intravenous Tolerance Test) - Disposition Index (DI)	After treatment (6 weeks)	Disposition Index (DI) is the product of sensitivity index (SI) by the amount of insulin secreted in response to blood glucose levels. It is a marker of the risk of type 2 diabetes. Low DI reflects a high risk of diabetes. DI can vary from 0 to an undefined upper limit. The physiological range for the Disposition Index is 500 to 5,000. Higher values represent a better outcome.
IVGTT (Intravenous Tolerance Test) - Sensitivity Index (SI)	After treatment (6 weeks)	Sensitivity Index (SI): a measure of how much insulin the body needs to metabolize a given amount of glucose. SI is calculated using a mathematical model describing the profiles of blood glucose and serum insulin after intravenous glucose injection. SI varies from 0 to an undefined upper limit but generally under 20. Higher values of SI represent a better outcome.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Men With OSA Obese men and pre-menopausal women with OSA will receive 6 weeks of CPAP treatment, and assessed with a 3-day experimental protocol. CPAP: CPAP (continuous positive airway pressure) treatment at home for 6 weeks	10
Women With OSA Obese men and pre-menopausal women with OSA will receive 6 weeks of CPAP treatment, and assessed with a 3-day experimental protocol. CPAP: CPAP (continuous positive airway pressure) treatment at home for 6 weeks	4
Men Without OSA Obese men and pre-menopausal women without OSA will be characterized with a single 3-day experimental protocol	3
Women Without OSA Obese men and pre-menopausal women without OSA will be characterized with a single 3-day experimental protocol	10
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Withdrawal by Subject	1	0	0	0

Baseline characteristics

Characteristic	Men With OSA	Total	Women Without OSA	Men Without OSA	Women With OSA
Age, Continuous	37.7 years STANDARD_DEVIATION 6.5	33.7 years STANDARD_DEVIATION 7.2	31.9 years STANDARD_DEVIATION 7.4	24.7 years STANDARD_DEVIATION 1.5	35 years STANDARD_DEVIATION 2.9
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	15 Participants	7 Participants	2 Participants	4 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	8 Participants	12 Participants	3 Participants	1 Participants	0 Participants
Sex: Female, Male Female	0 Participants	14 Participants	10 Participants	0 Participants	4 Participants
Sex: Female, Male Male	10 Participants	13 Participants	0 Participants	3 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 13	0 / 13
other Total, other adverse events	0 / 13	0 / 13
serious Total, serious adverse events	0 / 13	0 / 13

Outcome results

Primary

Polysomnography - Apnea-hypopnea Index (AHI)

apnea-hypopnea index: number of apneas and hypopneas per hour of recording; a measure of the severity of obstructive sleep apnea; varies from min=0 to max=120; AHI between 0 and \<5: no significant sleep apnea; AHI between 5 and \<15: mild sleep apnea; AHI between 15 and \<30: moderate sleep apnea; AHI of 30 and above: severe sleep apnea.

Time frame: After 6 weeks of CPAP (Treatment)