Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00300872 |
| Other study ID # |
Resp/hui/2006/002 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 2005 |
| Est. completion date |
August 6, 2019 |
Study information
| Verified date |
January 2021 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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).
Ambulatory Blood Pressure Monitoring(ABPM):
All patients with obstructive sleep apnea (OSA) will be fitted with the Ultralite Ambulatory
Blood Pressure Monitoring (ABPM) (Spacelabs Medical, Redmond, WA) via an arm cuff as
out-patients during normal activities and monitored for 48 hrs prior to commencement of
therapeutic or sham continuous positive airway pressure (CPAP) treatment. The patients' arm
circumference will be measured at the biceps level and an appropriate sized arm cuff will be
applied. The machine will be programmed for cuff inflation measurement every 30 minutes for
48 hrs and can only be removed for bathing. Patients will be asked to abstain from
caffeine-containing products during this time but to continue their normal daily activities.
Patients will record the time they retire to bed and the subsequent time of waking in order
to identify the sleep period. Data gathered before 6pm on the second evening will be
discarded to allow for acclimatization and the analysis will be performed with the second 24
hr of data (6pm to 6am).6 Data will be manually checked for artifact by our respiratory
fellow, who will be blinded to the treatment status of the patient. Forty-eight hrs before
the end of the therapeutic or sham continuous positive airway pressure (CPAP) at 3 months,
the patients will be fitted with the Ambulatory Blood Pressure Monitoring(ABPM) machine and
the same procedure repeated.
Measurement of blood samples:
Fifteen ml of fasting venous blood will be taken from each patient after the overnight PSG.
Plasma will be separated within 2 hours in a refrigerated centrifuge, aliquoted and stored at
-70C until assayed. Plasma VEGF will be measured by a quantitative enzyme-linked immunoassay
technique using a commercially available kit (R & D Systems, Abingdon, UK). Serum lipids will
be checked as it has been reported that Vascular endothelial growth factor (VEGF) also
increases in patients with hyperlipidemia, with and without atherosclerosis.7
Therapeutic continuous positive airway pressure (CPAP) vs Sham placebo:
Patients in the therapeutic continuous positive airway pressure (CPAP) or sham continuous
positive airway pressure (CPAP) treatment arm will be offered a 30-minute daytime trial of
nasal continuous positive airway pressure (CPAP) treatment. Each patient will be given a
basic continuous positive airway pressure (CPAP) education program by our respiratory nurse
supplemented by education brochure.4 The nurse will fit a comfortable continuous positive
airway pressure (CPAP) mask from a wide range of selection for the patient, who will then be
given a short trial of continuous positive airway pressure (CPAP) therapy with the Autoset
(Resmed, Sydney, Australia) continuous positive airway pressure (CPAP) device for those in
the therapeutic continuous positive airway pressure (CPAP) arm for approximately 30 minutes
for acclimatization in the afternoon. Attended continuous positive airway pressure (CPAP)
titration will be performed with the Autoset auto-titrating device on the second night of the
PSG study for the group randomized to the therapeutic continuous positive airway pressure
(CPAP) arm.2-4 All the patients in the therapeutic continuous positive airway pressure (CPAP)
arm will be prescribed the Horizon LT 8001 continuous positive airway pressure (CPAP) device
(De Vilbiss, Somerset, PA, USA) with a time counter recording machine run time. The
continuous positive airway pressure (CPAP) pressure for each patient will be set at the
minimum pressure needed to abolish snoring, obstructive respiratory events and airflow
limitation for 95% of the night as determined by the overnight Autoset continuous positive
airway pressure (CPAP) titration study.
The patients randomized to the subtherapeutic continuous positive airway pressure (CPAP) arm
will have the CPAP units set to the lowest pressure (4 cm of water pressure) and 6 extra 4mm
holes will be inserted in the collar of the main tubing at the end of the mask to allow air
escape and to prevent carbon dioxide rebreathing.8,9 They will be given a trial of 30 minutes
for acclimatization before starting continuous positive airway pressure (CPAP) at home.
All the patients in each arm will be followed up at the Respiratory clinic separately at 1
month and 3 months and the objective continuous positive airway pressure (CPAP) compliance
will be measured from the time counter. Although the 2 different treatment arms are explained
in the patient information, the patients will not be aware of whether they are receiving
therapeutic or sham continuous positive airway pressure (CPAP). The research nurse
responsible for randomization of patients to different treatment arms will not participate in
outcome assessments, which will be conducted by a different team of nurses who are not aware
of the randomization status of the patients.9 At the end of the study (ie 3 months), all
patients in the subtherapeutic continuous positive airway pressure (CPAP) arm will be
readmitted for AutoSet continuous positive airway pressure (CPAP) titration to establish
their long-term therapeutic pressure.
Other outcome assessment:
Prior to commencement of nasal therapeutic or sham continuous positive airway pressure
(CPAP), all patients have to go through several measurements. These include assessment of
subjective sleepiness with the Epworth sleepiness scale (ESS)10, quality of life with the
Calgary Sleep Apnea Quality of Life Index (SAQLI).11 The ESS is a questionnaire specific to
symptoms of daytime sleepiness and the patients are asked to score the likelihood of falling
asleep in eight different situations with different levels of stimulation, adding up to a
total score of 0 to 24.10 The Calgary Sleep Apnea Quality of Life Index (SAQLI) has 35
questions organized into four domains: daily functioning, social interactions, emotional
functioning and symptoms with a fifth domain, treatment-related symptoms, to record the
possible negative impacts of treatment. The Sleep Apnea Quality of Life Index (SAQLI) has a
high degree of internal consistency, face validity as judged by content experts and patients
and construct validity as shown by its positive correlations with the Short Form-36 Health
Survey questionnaire (SF-36) and the improvement in scores in patients successfully
completing a 4 weeks' trial of continuous positive airway pressure (CPAP).11 It contains
items shown to be important to patients with sleep apnea and is designed as a measure of
outcome in clinical trials in sleep apnea, and has been applied previously in our Chinese
obstructive sleep apnea (OSA) patients on continuous positive airway pressure (CPAP). 4 All
patients will have to complete the Epworth Sleepiness Score (ESS) and Sleep Apnea Quality of
Life Index (SAQLI) at baseline, 1 month and 3 months after treatment.
