Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00300872
Status:
COMPLETED
Last Update Posted:
2021-01-27
First Post:
2006-03-08
Brief Title:
Effect of Nasal Continuous Positive Airway Pressure CPAP Blood Pressure and Vascular Endothelial Growth Factor in Obstructive Sleep Apnea Syndrome
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
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
Status:
COMPLETED
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ie 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
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 concentration1 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 USAand supplemented by an oral thermister and finger pulse oximetry as in our previous studies2-4 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 10hr 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 MonitoringABPM
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 6am6 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 MonitoringABPM 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 atherosclerosis7
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 brochure4 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 arm2-4 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 rebreathing89 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 patients9 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 ESS10 quality of life with the Calgary Sleep Apnea Quality of Life Index SAQLI11 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 2410 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 CPAP11 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
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 concentration1 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 USAand supplemented by an oral thermister and finger pulse oximetry as in our previous studies2-4 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 10hr 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 MonitoringABPM
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 6am6 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 MonitoringABPM 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 atherosclerosis7
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 brochure4 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 arm2-4 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 rebreathing89 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 patients9 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 ESS10 quality of life with the Calgary Sleep Apnea Quality of Life Index SAQLI11 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 2410 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 CPAP11 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None