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Biomarkers for Obstructive Sleep Apnea

2014-08-27 03:24:39 | BioPortfolio

Summary

The purpose of the study is to:

- recruit subjects with untreated sleep apnea; assess overnight changes in their blood and urine chemicals

- review the overnight changes in blood and urine chemicals after they have been treated for sleep apnea

- assess the overnight changes in blood and urine chemicals in healthy individuals with no sleep problems

- compare the amount of fat in the belly using a Magnetic Resonance Imaging (MRI) scanner on all subjects

Description

The overall goal of this project is to address the postulate that the optimal molecular signature for the common disorder obstructive sleep apnea (OSA) is change in relevant biomarkers during the sleep period. In sleep apnea, events lead to sleep fragmentation and cyclical deoxygenation/reoxygenation. It is proposed that these changes will lead to molecular consequences can be detected by assessing biomarkers in blood. To determine which changes are due to OSA and which to circadian/sleep mechanisms, studies will be done in patients with OSA before and after effective treatment with CPAP and also in controls of similar visceral adiposity without OSA. Multiple assessments of biomarkers will be made before, during and after sleep. Since it is proposed that the magnitude of these dynamic changes across the sleep period will be affected by degree of visceral obesity and be greater in OSA subjects with cardiovascular comorbidities, studies will be done in 4 groups of subjects: lean and obese with and without such morbidities. In assessing biomarkers the primary outcome variables will be: urinary isoprostanes (oxidative stress); plasma TNFα (inflammation); plasma norepinephrine (sympathetic activation); and free fatty acids. Secondary biomarkers will be: IL-6, urinary norepinephrine; urinary normetanephrine; glucose, ICAM, leptin. To complement assessment of circulating biomarkers, an approach utilizing a cellular window will be used. Monocytes will be separated from each blood sample (before, during and after sleep) and RNA extracted. Expression of key genes will be assessed by RT-PCR and microarray studies will be performed in a subset of subjects to assess changes in expression of all genes as a result of OSA. A particular focus will be investigating differences between individuals with OSA with and without cardiovascular comorbidities. Three aspects will be evaluated: a)whether individuals with comorbidities have more oxidative stress and inflammatory change for equivalent degrees of OSA than individuals without such comorbidities; b) whether individuals with comorbidities have lower levels of protective mechanisms—melatonin (an anti-oxidant secreted during sleep), IL-10 (antiinflammatory); c) different gene variants based on a genetic association study using a recently developed CV SNP array. Finally, data will be used to determine whether there is a diagnostic urine and/or blood test for OSA.

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Conditions

Obstructive Sleep Apnea (OSA)

Intervention

CPAP

Location

University of Pennsylvania
Philadelphia
Pennsylvania
United States
19104

Status

Recruiting

Source

University of Pennsylvania

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:24:39-0400

Clinical Trials [2221 Associated Clinical Trials listed on BioPortfolio]

Metabolic Impact of Intermittent CPAP

Obstructive sleep apnea is a risk factor for diabetes and cardiovascular disease, by unknown mechanisms. The investigators hypothesize that sleep apnea changes glucose and lipid metabolism...

Effect of CPAP on Myocardial Dysfunction in Type 2 Diabetes Mellitus and Obstructive Sleep Apnea Patients

This study evaluates the effect of the use of nasal CPAP in the cardiac function, measured by strain and TEI index, in patients with type 2 diabetes mellitus, obstructive sleep apnea and o...

Feasibility Evaluation of CPAP in the Treatment of Obstructive Sleep Apnea Synchrone in the Acute Phase of Stroke

This project is focused on the treatment of obstructive sleep apnea in the acute phase of stroke. Stroke is a frequent pathology with a high morbidity and mortality rate. Although it has n...

Evaluating Behavioral Treatments to Improve Adherence to CPAP in People With Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a serious sleep disorder in which a person repeatedly stops breathing or experiences shallow breathing for short periods of time during sleep. The most com...

Weight Gain After CPAP Treatment in Patients With Obstructive Sleep Apnea

The purpose of this trial is to investigate the mechanisms leading to weight gain during CPAP treatment for obstructive sleep apnea (OSA).

PubMed Articles [2070 Associated PubMed Articles listed on BioPortfolio]

Pulmonary rehabilitation and oropharyngeal exercises as an adjunct therapy in obstructive sleep apnea: a randomized controlled trial.

It is well recognized that the most effective treatment for obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Different treatment possibilities comprise surgery, mandibular ...

Magnetic resonance imaging of obstructive sleep apnea in children.

Sleep-disordered breathing has a spectrum of severity that spans from snoring and partial airway collapse with increased upper airway resistance, to complete upper airway obstruction with obstructive ...

Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study.

Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) is crucial. Our aim was to identify protective and risk factors against the discontinuation of CP...

Obstructive sleep apnea and the effect of CPAP treatment on ischemia-modified albumin levels: a multi effect size meta-analysis with diagnostic test accuracy.

A close association of oxidative stress (OS) and ischemia-modified albumin (IMA) with obstructive sleep apnea (OSA) has been reported in the literature, but the results on IMA are ambiguous. We conduc...

Successful Treatment of Extremely Severe Obstructive Sleep Apnea with a Dental Appliance.

A dental appliance for obstructive sleep apnea (OSA) is recommended for patients who cannot adjust to continuous positive airway pressure (CPAP) treatments.

Medical and Biotech [MESH] Definitions

A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration. This condition may be idiopathic (primary) or associated with lower brain stem lesions; chronic obstructive pulmonary disease (LUNG DISEASES, OBSTRUCTIVE); HEART FAILURE, CONGESTIVE; medication effect; and other conditions. Sleep maintenance is impaired, resulting in daytime hypersomnolence. Primary central sleep apnea is frequently associated with obstructive sleep apnea. When both forms are present the condition is referred to as mixed sleep apnea (see SLEEP APNEA SYNDROMES). (Adams et al., Principles of Neurology, 6th ed, p395; Neurol Clin 1996;14(3):611-28)

Disorders characterized by multiple cessations of respirations during sleep that induce partial arousals and interfere with the maintenance of sleep. Sleep apnea syndromes are divided into central (see SLEEP APNEA, CENTRAL), obstructive (see SLEEP APNEA, OBSTRUCTIVE), and mixed central-obstructive types.

Dyssomnias (i.e., insomnias or hypersomnias) associated with dysfunction of internal sleep mechanisms or secondary to a sleep-related medical disorder (e.g., sleep apnea, post-traumatic sleep disorders, etc.). (From Thorpy, Sleep Disorders Medicine, 1994, p187)

A disorder characterized by recurrent apneas during sleep despite persistent respiratory efforts. It is due to upper airway obstruction. The respiratory pauses may induce HYPERCAPNIA or HYPOXIA. Cardiac arrhythmias and elevation of systemic and pulmonary arterial pressures may occur. Frequent partial arousals occur throughout sleep, resulting in relative SLEEP DEPRIVATION and daytime tiredness. Associated conditions include OBESITY; ACROMEGALY; MYXEDEMA; micrognathia; MYOTONIC DYSTROPHY; adenotonsilar dystrophy; and NEUROMUSCULAR DISEASES. (From Adams et al., Principles of Neurology, 6th ed, p395)

HYPOVENTILATION syndrome in very obese persons with excessive ADIPOSE TISSUE around the ABDOMEN and DIAPHRAGM. It is characterized by diminished to absent ventilatory chemoresponsiveness; chronic HYPOXIA; HYPERCAPNIA; POLYCYTHEMIA; and long periods of sleep during day and night (HYPERSOMNOLENCE). It is a condition often related to OBSTRUCTIVE SLEEP APNEA but can occur separately.

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