The Role of Oxidative Stress in the Cardiovascular Consequences of Sleep Apnea

Sleep Apnea Clinical Trial

Official title:

The Role of Oxidative Stress in the Cardiovascular Consequences of Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701441
• Other study ID #: 2005H0221
• Status: Completed
• Phase: N/A
• First received: May 15, 2008
• Last updated: October 29, 2013
• Start date: February 2007
• Est. completion date: June 2010

Study information

• Verified date: October 2013
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Obstructive Sleep Apnea (OSA) is the most common sleep disorder affecting up to 9-24 percent of middle aged adults, and is becoming increasingly implicated in the pathogenesis of hypertension, and other cardiovascular disorders. Up to half of patients with OSA have hypertension, and their risk of developing hypertension increases with the increasing severity of Sleep Apnea. Patients with OSA and no hypertension have endothelial dysfunction, which is believed to be the precursor for most cardiovascular disorders.

The upper airway collapse and obstruction that occur in OSA result in a pattern of intermittent hypoxia, that has been shown to be the cause of the hypertension, and endothelial dysfunction found in patients with OSA. Intermittent hypoxia results in oxidative stress, which in turn is linked to the pathogenesis of hypertension and endothelial dysfunction.

This protocol evaluates the role of the oxidative stress in endothelial function and blood pressure in patients with OSA. This is a pilot clinical study that will compare oxidative stress parameters, and endothelial function in patients with OSA before starting treatment with continuous positive airway pressure (CPAP) and 12 weeks post being on CPAP. These patients will be compared to control patients with no history of OSA. the study does not involve assignement to different treatments. All patients will receive the indicated treatment for OSA and measurements will be collected before and 12 weeks after adequate treatment.

Description:

Obstructive Sleep Apnea (OSA) is increasingly recognized as a cardiovascular risk factor. OSA is a cause of hypertension and has strong association with atherosclerosis, coronary heart disease, diabetes stroke , and fatal cardiovascular events. Endothelial dysfunction is a preclinical vascular abnormality that predicts subsequent development of vascular disease . Patients with OSA demonstrate endothelial dysfunction in the absence of any manifested vascular disease . The mechanism of endothelial dysfunction in OSA is largely unknown. Endothelial dysfunction in OSA is reversible with antioxidants, suggesting a role for oxidant overproduction in the decreased NO availability in OSA. This provides parallels to other cardiovascular diseases in which oxidative stress induced endothelial dysfunction is important.

Recent studies reported evidence of dysfunction or decreased expression of endothelial nitric oxide synthase (eNOS) in association with increased peroxynitrite in harvested venous endothelial cells of OSA patients. We endeavored to perform the first direct quantification of microvascular endothelial genes from OSA patients. We hypothesized that patients with OSA who are free of any cardiovascular disease will have early functional changes in the microcirculatory endothelial cells that are associated with OSA, and therefore would resolve with treatment. Given the role of oxidative stress in the vascular disease of OSA, we expected to find evidence of superoxide overproduction in the microcirculatory vessels. We expected these functional changes to be reversible with treatment of OSA.

Measurement of superoxide will be done on the subcutaneous biopsy tissue using quantitative Polymerase Chain Reaction (qPCR) and immunohistochemistry techniques and image analysis software. Measurement of endothelial function will be done using Doppler ultrasound.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Completed sleep study - Older than 18

Exclusion Criteria:

• Hypertension

• Diabetes

• coronary disease

• Peripheral vascular disease

• High cholesterol

• Smoking

• Pregnancy

• Use of erectile dysfunction medications or supplements

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea
• Sleep Apnea Syndromes

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Rami Khayat

Country where clinical trial is conducted

United States, 

References & Publications (1)

Patt BT, Jarjoura D, Haddad DN, Sen CK, Roy S, Flavahan NA, Khayat RN. Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2010 Dec 15;182(12):1540-5. doi: 10.1164/rccm.201002-0162OC. Epub 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peroxynitrite Deposition in the Vascular Walls	A forearm biopsy will be collected to isolate human microcirculatory endothelial cells. The stain density of peroxynitrite, an indicator of oxidative stress, in the vascular walls is compared between pre-treatment and post treatment patient tissue. Also another comparison is made between pre-treatment and control tissue. The stain density is a software-generated measurement of pixel intensity and is considered to be an arbitrary unit. Higher numbers indicate greater density	baseline and 12 weeks	No
Primary	Flow Mediated Dilation	A non-invasive test using an ultrasound to measure baseline resting vessel diameter and vessel wall dilation in upper arm post application of an inflated blood pressure cuff for five minutes. The percentage change in vessel wall dilation due to stimulation from the resting vessel diameter will be calculated for each group of participants. The results will be compared relative to each group of participants.	Baseline and 12 weeks	No