A Randomized, Placebo-controlled Study of the Medium-term Effect of Nasal CPAP on 24 Hour Blood Pressure and Vascular Endothelial Growth Factor in Obstructive Sleep Apnea Syndrome
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 140
- Locations
- 1
- Primary Endpoint
- Change in 24 hr mean blood pressure at 3 months
Study Overview
Brief Summary
Sleep-disordered breathing (SDB) briefly means cessation of breathing during sleep at least 5 times per hour. SDB is a common disorder affecting 9 to 24% of the middle-aged and overall 4% of the middle-aged male population suffers from the Obstructive sleep apnea syndrome (OSA) i.e. Sleep-disordered breathing (SDB) with associated daytime sleepiness. Several major epidemiological studies have shown that SDB is not only an independent risk factor for hypertension but it is also strongly associated with heart failure and stroke. The mechanism for the linkage between SDB and cardiovascular consequences is not fully determined. Vascular endothelial growth factor (VEGF) is a soluble 34-46 kD angiogenic heparin-binding glycoprotein. This cytokine regulates multiple endothelial cell functions including vascular permeability and vascular tone and some data suggest that it may contribute to the atherosclerotic process. Recent studies have shown increased plasma and serum concentrations of Vascular endothelial growth factor (VEGF) in patients with OSA and there were correlations between VEGF concentrations and the severity of OSA, as indexed by the minimum oxygen saturation level and the frequency of the upper airway obstruction per hour of sleep. A recent non-randomized study with a small sample size has shown a significant decrease in Vascular endothelial growth factor (VEGF) concentrations in patients in whom nocturnal hypoxia improved after 1 year of nasal continuous positive airway pressure (CPAP) therapy.
Despite robust evidence showing improvement of symptoms, cognitive function and quality of life in obstructive sleep apnea (OSA) patients treated with nasal CPAP, there are nevertheless conflicting data whether Continuous positive airway pressure (CPAP) can reduce daytime blood pressure (BP) in patients with OSA. Two randomized placebo controlled studies have shown reduction of 24-hr systolic and diastolic blood pressure (BP) in obstructive sleep apnea (OSA) patients after 1 month of nasal continuous positive airway pressure (CPAP) therapy while other investigators have shown no such benefit.
This randomized, sham-placebo controlled study aims to assess 1) the effect of nasal continuous positive airway pressure (CPAP) over a period of 3 months on 24 hr blood pressure (BP); and 2) whether any change in BP and plasma Vascular endothelial growth factor (VEGF) is related to the baseline severity of obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) compliance.
Detailed Description
Subjects and Methods:
We propose to carry out a prospective, randomized sham placebo-controlled parallel study on 140 consecutive patients newly diagnosed with OSA, as defined by overnight sleep study showing apnea hypopnea index (AHI) >10 per hour of sleep plus excessive daytime sleepiness or two of the following symptoms: choking or gasping during sleep, recurrent awakenings from sleep, unrefreshed sleep, daytime fatigue and impaired concentration.1 The patients will be recruited from the Respiratory Clinic, Prince of Wales Hospital, Shatin, HK.
Sleep assessment:
Overnight diagnostic polysomnography (PSG) [Healthdyne Alice 4, USA] will be performed for every subject on the first night recording electroencephalogram, electro-oculogram, submental electromyogram, bilateral anterior tibial electromyogram, electrocardiogram, chest and abdominal wall movement by inductance plethysmography, airflow measured by a nasal pressure transducer [PTAF2, Pro-Tech, Woodinville, WA, USA]and supplemented by an oral thermister, and finger pulse oximetry as in our previous studies.2-4 Sleep stages will be scored according to standard criteria by Rechtshaffen and Kales. 5 Apnoea is defined as cessation of airflow for > 10 seconds and hypopnea as a reduction of airflow of >50% for > 10 seconds plus an oxygen desaturation of > 3% or an arousal.
Following confirmation of significant obstructive sleep apnea syndrome (OSA) from the overnight sleep study with apnea hypopnea index (AHI) >10/hr, each patient will be interviewed by the physician on duty and randomized into 2 groups receiving either nasal therapeutic continuous positive airway pressure (CPAP) treatment or sham continuous positive airway pressure (CPAP), via a balanced block design, after completion of recording of 24 hr ambulatory blood pressure (BP).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 20 to 80 yrs
- •Apnea hypopnea index (AHI) > 10/hr on Polysomnograph (PSG) with symptoms of obstructive sleep apnea (OSA) as described previously
- •Epworth Sleepiness Scale (ESS) >10
- •Patients with hypertension will still be eligible to enter and continue the study as long as there is no alteration of anti-hypertensive medications during the study period
Exclusion Criteria
- •Patients having problems staying awake during driving, shift work
- •Recent myocardial infarction
- •Unstable angina
- •Underlying malignancy
Arms & Interventions
1
Continuous positive airway pressure (CPAP)
Intervention: Continuous positive airway pressure (CPAP) (Device)
2
Sham Continuous positive airway pressure (CPAP)
Intervention: Sham Continuous positive airway pressure (CPAP) (Device)
Outcomes
Primary Outcomes
Change in 24 hr mean blood pressure at 3 months
Time Frame: baseline and 3 months
Secondary Outcomes
- Whether any change in blood pressure or vascular endothelial growth factor (VEGF) is related to the baseline severity of obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) compliance over 3 months(baseline and 3 months)
- Changes in systolic and diastolic blood pressure, changes in mean blood pressure awake and asleep, change in plasma Vascular endothelia growth factor (VEGF) at 3 months(baseline and 3 months)
- Epworth Sleepiness Scale (ESS) and Calgary Sleep Apnea Quality of Life Index (SAQLI) at 1 month and 3 months.(baseline and 3 months)
Investigators
Prof David Shu Cheong Hui
Prof
Chinese University of Hong Kong