Biomarkers for Obstructive Sleep Apnea

NCT ID: NCT00834509

Last Updated: 2017-04-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 181 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2015-02-01

Brief 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

Detailed 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 Continuous Positive Airway Pressure (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 tumor necrosis factor alpha (TNFα) (inflammation); plasma norepinephrine (sympathetic activation); and free fatty acids. Secondary biomarkers will be: Interleukin 6 (IL-6), urinary norepinephrine; urinary normetanephrine; glucose, Intercellular Adhesion Molecule (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.

Conditions

Obstructive Sleep Apnea (OSA)

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Obstructive Sleep Apnea (OSA)

OSA participants will be treated with a CPAP/APAP treatment, per standard clinical care.

CPAP

Intervention Type: DEVICE

Use CPAP for 4-6 weeks as clinically prescribed.

Control

Control participants will not receive APAP/CPAP treatment, if not diagnosed with OSA.

No interventions assigned to this group

Interventions

CPAP

Use CPAP for 4-6 weeks as clinically prescribed.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• able to read and write in English
• if female, not pregnant
• goes to bed between 9:30pm-12:30am and sleeps minimum of 7 hours/night
• has telephone access
• BMI < 40

Exclusion Criteria

• shift worker, irregular schedule
• previous diagnosis of sleep disorder other than OSA
• previous treatment with CPAP, BiPAP, oxygen, surgery for OSA
• current kidney disease, anemia, depression,
• substance abuse/dependence
• BMI > 40
• visual/hearing/cognitive impairments
• smoker who's not willing to refrain from all nicotine during study
• not willing to try CPAP treatment

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Allan Pack

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Allan I Pack, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

Lim DC, Brady DC, Po P, Chuang LP, Marcondes L, Kim EY, Keenan BT, Guo X, Maislin G, Galante RJ, Pack AI. Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia. J Appl Physiol (1985). 2015 Mar 1;118(5):544-57. doi: 10.1152/japplphysiol.00629.2014. Epub 2014 Nov 26.

Reference Type: DERIVED

PMID: 25429097 (View on PubMed)

Other Identifiers

P01HL094307

Identifier Type: NIH

Identifier Source: secondary_id

View Link

807416

Identifier Type: -

Identifier Source: org_study_id