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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2008 by National Institute on Aging (NIA).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00177892
First received: September 13, 2005
Last updated: February 28, 2008
Last verified: February 2008

September 13, 2005
February 28, 2008
September 2003
August 2008   (final data collection date for 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 ] [ Designated as safety issue: Yes ]
  • -To determine the effect of Sleep Fragmentation on oxidative stress and inflammation and features of the Metabolic Syndrome.
  • -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.
  • -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.
  • -To explore if specific gene expression patterns after the study conditions are associated with alterations consistent with Metabolic Syndrome.
Complete list of historical versions of study NCT00177892 on ClinicalTrials.gov Archive Site
Not Provided
-To exploratore the correlation among genetic variations (polymorphisms), gene expression patterns (microarray) and resultant protein production (proteomics).
Not Provided
Not Provided
 
Obstructive Sleep Apnea (OSA) and Metabolic Syndrome: Role of Oxidative Stress
OSA and Metabolic Syndrome: Role of Oxidative Stress

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
  • Obstructive Sleep Apnea
  • Metabolic Syndrome X
  • Procedure: sleep disruption
    experimentally-induced Sleep Fragmentation
  • Procedure: sleep with and without positive pressure
    OSAH patients with and without chronic positive airway pressure therapy
    Other Names:
    • fragmentation + normoxia
    • fragmentation + hypoxia
  • Experimental: 1
    non-OSAH/overweight individuals with the Metabolic Syndrome
    Intervention: Procedure: sleep disruption
  • Experimental: 2
    non-OSAH/overweight individuals without Metabolic Syndrome
    Intervention: Procedure: sleep disruption
  • Active Comparator: 3
    non-OSAH/normal weight without Metabolic Syndrome
    Intervention: Procedure: sleep disruption
  • Experimental: 4
    OSAH patients with chronic positive airway pressure therapy
    Intervention: Procedure: sleep with and without positive pressure
  • Experimental: 5
    OSAH patients without chronic positive airway pressure therapy
    Intervention: Procedure: sleep with and without positive pressure
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
76
August 2008
August 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
Yes
Contact: Lynnette Robinson, BS 412-647-1345 robinsonlm@upmc.edu
Contact: Mark H Sanders, MD 412-692-2880 sandersmh@upmc.edu
United States
 
NCT00177892
AG0089, 5R01AG023977
Yes
Mark H Sanders, MD, University of Pittsburgh School of Medicine
National Institute on Aging (NIA)
University of Pittsburgh
Principal Investigator: Mark H Sanders, MD University of Pittsburgh
National Institute on Aging (NIA)
February 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP