Sleep Apnea and Oxidative Stress and Nitric Oxide

Nitrate and Oxidative Stress in Sleep Apnea Syndrome. Effect of Continuous Positive Airway Pressure

Background: Previous studies present contradictory data concerning obstructive sleep apnea syndrome (OSAS), lipid oxidation and nitric oxide (NO) bioavailability. This study was aimed: (1) to compare the concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma of middle aged males with OSAS and no other known comorbidity and carefully matched healthy controls of the same age and gender; and (2) to test the hypothesis that nasal continuous positive airway pressure (CPAP) therapy, might attenuate oxidative stress and nitrate deficiency.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea Syndromes
• Intervention / Treatment: Device: nasal continuous positive airway pressure (CPAP) therapy

Detailed Description

We performed a single-center, prospective, randomized, double-blind, placebo-controlled and cross-over clinical study, in which patients received CPAP and sham therapy for two 12-week periods. Baseline measurements in healthy controls matched for age and gender were also obtained. At recruitment, 24-h blood pressure monitoring (ABPM), an echocardiogram (to rule out any cardiac dysfunction) and a sleep study was obtained in all participants . After fasting overnight, a venous blood sample (anti-coagulated with dipotassium EDTA, for 8-isoprostane and total nitrate and nitrite concentration (NOx) determinations) and a urine sample were collected in all of them between 08:00 and 10:00 hours. Within 30 minutes of blood collection, plasma was obtained by centrifugation at 3000 rpm for 15 min. All plasma samples were stored at -60°C until analysis. Patients with OSAS underwent a full-night CPAP titration study using an automated pressure setting device (Auto Set; ResMed, Sydney, Australia). Compliance with therapy was obtained from a built-in run-time counter. After 12 weeks, CPAP device was switched to the alternate mode of therapy and ABPM,, plasma and urine sampling were repeated in patients

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• apnea-hypopnea index (AHI) ≥10 h-1
• excessive daytime sleepiness defined by an Epworth scale score ≥11 points
• no treatment for OSAS. Inclusion criteria for healthy control subjects were AHI <5 h-1 and Epworth sleepiness scale <10.

Exclusion Criteria:

• unwillingness or inability to participate in the study
• obstructive or restrictive lung disease as identified by pulmonary function testing
• use of cardioactive drugs
• cardiac rhythm disturbances, including sinus bradycardia and sinus tachycardia
• known arterial hypertension, or 24-hour mean blood pressure of 135 and/or 85 mm Hg or more
• left ventricular ejection fraction <50%, ischemic or valve heart disease, hypertrophic, restrictive or infiltrative cardiomyopathy, pericardial disease or stroke, by history, physical examination, ECG, chest radiography, conventional exercise stress testing, and echocardiography
• diabetes mellitus, by history or 2 random blood glucose levels ≥126 mg/dl
• morbid obesity (body mass index >40 Kg/m2)
• daytime hypoxemia (PaO2 <70 mm Hg) or hypercapnia (PaCO2 >45 mm Hg)
• need to change medication
• hospital admission for 10 or more days
• average nightly CPAP usage less than 3.5 hours.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: CPAP	Device: nasal continuous positive airway pressure (CPAP) therapy; Nocturnal ventilation through a nasal mask to avoid sleep apneas
SHAM_COMPARATOR: Sham-CPAP; The sham CPAP device consisted of a conventional CPAP device, in which the area of the exhalation port was amplified, thereby nearly cancelling nasal pressure; an orifice resistor was connected between the tubing and the CPAP unit that loads the blower with the same airflow resistance as in effective CPAP	Device: nasal continuous positive airway pressure (CPAP) therapy; Nocturnal ventilation through a nasal mask to avoid sleep apneas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
concentration of 8-isoprostane and total nitrate and nitrite (NOx) in plasma	3 months

Collaborators and Investigators

• Sponsor: Sociedad Española de Neumología y Cirugía Torácica
• Collaborators: Fondo de Investigacion Sanitaria

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Study Completion (ACTUAL): December 1, 2003

Study Registration Dates

• First Submitted: October 22, 2007
• First Submitted That Met QC Criteria: October 22, 2007
• First Posted (ESTIMATE): October 23, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): November 9, 2007
• Last Update Submitted That Met QC Criteria: November 7, 2007
• Last Verified: October 1, 2007

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Sleep Apnea; Oxidative Stress; Nitric oxide
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disease; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Syndrome; Apnea
• Other Study ID Numbers: NO-OE-SAHS