Expired Study
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Pittsburgh, Pennsylvania 15261


Purpose:

The purpose of this study is to define the mechanism(s) through which Obstructive Sleep Apnea/Hypopnea (OSAH) promotes abnormal metabolic processes which characterize the metabolic syndrome. The investigators hypothesize that the sleep fragmentation and intermittent sleep hypoxia which occur in OSAH patients promote oxidative stress and inflammation which in turn lead to insulin resistance, dyslipidemia, abnormal vascular reactivity and other processes which are consistent with the metabolic syndrome.


Study summary:

The metabolic syndrome has been defined as insulin resistance, central obesity, systemic hypertension and dyslipidemia and is associated with increased cardiovascular (CV) risk. Obstructive Sleep Apnea-Hypopnea (OSAH) is also associated with increased CV risk and insulin resistance. Since OSAH is associated with oxidative stress and pro-inflammatory processes, both of which are associated with insulin resistance, it follows that oxidative stress and inflammation may mediate the linkage between OSAH, insulin resistance and ultimately, the metabolic syndrome. The overall goal of this research is to test the hypothesis that oxidative stress and inflammation link OSAH to insulin resistance as well as other CV risk-promoting conditions reflecting the metabolic syndrome (e.g. hyperlipidemia). We will specifically test if the individual sleep consequences of OSAH, including sleep fragmentation and intermittent sleep hypoxia, promote oxidative stress and inflammation which in turn promote insulin resistance and other features of the metabolic syndrome. Aim 1a: To determine the effect of sleep fragmentation on oxidative stress and inflammation and features of the metabolic syndrome including insulin resistance, dyslipidemia, obesity, and hypertension. Aim 1b: To assess the interaction between pre-existing metabolic syndrome and the overweight condition without metabolic syndrome, with regard to the effects of sleep fragmentation on the study variables, we will contrast the effect of experimentally-induced sleep fragmentation in non-OSAH/overweight individuals with the metabolic syndrome, non-OSAH/overweight individuals without metabolic syndrome and a control group of non-OSAH/normal weight without metabolic syndrome. Aim: 2: To evaluate the effect of intermittent sleep hypoxia on oxidative stress and inflammation and explore the relationships between these two processes and insulin resistance, lipid profile, heart period variability and plasma cortisol. Aim: 3: Using microarray data from peripheral monocytes, we will explore if specific gene expression patterns after the study conditions are associated with alterations consistent with metabolic syndrome. Aim: 4: This exploratory aim is to collect preliminary data regarding the correlation among genetic variations (polymorphisms), gene expression patterns (microarray) and resultant protein production (proteomics). These data will be used for hypothesis development.


Criteria:

Inclusion Criteria: - Nonsmoker for at least 6 months - No history of movement disorder during sleep, or circadian rhythm disorder - No excessive daytime sleepiness - No history of chronic insomnia, mood or affective disorders or other psychiatric disorders - Participants maintain a regular sleep-wake pattern with an estimated sleep time between 6.5 and 10 hours per night - Ability and willingness to avoid meat with its juice (gravy), cured or smoked foods and green leafy vegetables, fruit and fruit juices, food products or vitamin supplements containing vitamin C and E supplements for at least 1 day prior to and during the study periods - Consumption of less than 1 alcoholic beverage per day - Ability to understand the study and sign the informed consent - Not currently pregnant - Live within 45 miles of the study site - No uncontrolled hypertension (blood pressure greater than 150/100) - Willingness to avoid caffeinated beverages and food during the study protocol period Participants With Sleep Apnea: - Diagnosis of severe Obstructive Sleep Apnea and Hypopnea (OSAH) (RDI greater than 25) and initiation of positive airway pressure therapy more than 1 month before enrollment - Must have had an adequate clinical titration of positive airway pressure therapy - On positive airway pressure for at least 1 month with adherence of more than 5 hours of use per day with no history of snoring, no excessive daytime sleepiness and no reported observed apnea episodes on positive airway pressure - Willing to sleep with and without positive airway pressure therapy as required by the study protocol Exclusion Criteria: - History or physical examination evidence of active coronary artery disease, heart failure, cardiomyopathy, syncope, potentially life-threatening arrhythmia, stroke, transient ischemic attack, neurologic impairment, renal, hepatic or thyroid disease (unless on stable thyroid replacement medication); history of diabetes mellitus; history of cancer within the past 10 years (other than basal cell carcinoma), venous thrombosis, or collagen-vascular disease or other condition that the investigators believe may be exacerbated by participation in the stud - History of awakening with angina pectoris - Currently taking medication for mood or affective disorders or that affect heme metabolism, autonomic nervous system or sleep architecture, or prescribed nitrates or corticosteroids - Physician-diagnosed Alzheimer's or non-Alzheimer's dementia - Previous surgery for sleep apnea - Hematocrit less than 32 - Use of a hearing aid in one or both ears - History of a bleeding disorder, abnormal bleeding, or known adverse reaction to heparin - Inability to obtain venous blood or a low likelihood of obtaining venous access as required in this protocol - History of migraine of a nature, frequency, and severity that, in the investigators' judgement, may be precipitated by participation in the protocol - Presence of a potentially life-threatening dysrhythmia on the clinical diagnostic PSG - History of motor vehicle accident due to falling asleep; not currently employed as a driver in the transportation industry or an airplane pilot - Lipid-lowering agents for participants without a history of sleep apnea - Individuals on positive airway pressure therapy for sleep apnea must not have lost more than 10 pounds of weight since starting this treatment


Study is Available At:


Original ID:

AG0089


NCT ID:

NCT00177892


Secondary ID:

5R01AG023977


Study Acronym:


Brief Title:

Obstructive Sleep Apnea (OSA) and Metabolic Syndrome: Role of Oxidative Stress


Official Title:

OSA and Metabolic Syndrome: Role of Oxidative Stress


Overall Status:

Recruiting


Study Phase:

N/A


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

65 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute on Aging (NIA)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificati


Number of Arms:

5


Number of Groups:

0


Total Enrollment:

76


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Mark H Sanders, MD
Principal Investigator
University of Pittsburgh
Primary Contact:Lynnette Robinson, BS
412-647-1345
robinsonlm@upmc.edu
Backup Contact:Mark H Sanders, MD
412-692-2880
sandersmh@upmc.edu

Study Dates

Start Date:September 2003
Completion Date:August 2008
Completion Type:Anticipated
Primary Completion Date:August 2008
Primary Completion Type:Anticipated
Verification Date:February 2008
Last Changed Date:February 28, 2008
First Received Date:September 13, 2005

Study Outcomes

Outcome Type:Primary Outcome
Measure:circulating and exhaled biomarkers of oxidative stress and pro-inflammatory cytokines, insulin resistance, lipid profile, plasma cortisol, and heart period variability (a reflection of sympathovagal tone)
Time Frame:before and after 2 consecutive nights
Safety Issues:True

Study Interventions

Intervention Type:Procedure
Name:sleep disruption
Description:experimentally-induced Sleep Fragmentation
Arm Name:1
Intervention Type:Procedure
Name:sleep with and without positive pressure
Description:OSAH patients with and without chronic positive airway pressure therapy
Arm Name:4
Other Name:fragmentation + normoxia

Study Arms

Study Arm Type:Experimental
Arm Name:5
Description:OSAH patients without chronic positive airway pressure therapy
Study Arm Type:Experimental
Arm Name:4
Description:OSAH patients with chronic positive airway pressure therapy
Study Arm Type:Active Comparator
Arm Name:3
Description:non-OSAH/normal weight without Metabolic Syndrome
Study Arm Type:Experimental
Arm Name:2
Description:non-OSAH/overweight individuals without Metabolic Syndrome
Study Arm Type:Experimental
Arm Name:1
Description:non-OSAH/overweight individuals with the Metabolic Syndrome

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute on Aging (NIA)
Agency Class:Other
Agency Type:Collaborator
Agency Name:University of Pittsburgh

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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