Clinical trial NCT02329470: Cardiovascular Effects After CPAP Withdrawal for Obstructive Sleep Apnea
Official title: Arterial Stiffness and Blood Pressure Changes After Continuous Positive Airway Pressure (CPAP) Withdrawal for Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Cardiovascular Disease
Lead sponsor: Umeå University
Sponsor class: OTHER
First posted: 2014-12-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Patients with obstructive sleep apnea run an increased risk of cardiovascular disease including hypertension. Continuous positive airway pressure (CPAP) is the first line of treatment. However, many patients skip CPAP for some nights.

Aims: The primary aim was to investigate the cardiovascular effects of short-term CPAP withdrawal for five nights because of obstructive sleep apnea.

Design: Randomized, parallel controlled trial Inclusion criteria: 100 patients with successful CPAP treatment for moderate to severe obstructive sleep apnea.

Exclusion criteria: Dementia, heart infarction within 3 months, apnea hypopnea index \> 10 with CPAP treatment.

Randomization: 50 patients are randomized to sleep 5 days without CPAP and 50 patients to continue with CPAP treatment during the trial.

Primary outcomes: Arterial stiffness, 24-hour blood pressure. Secondary outcomes: Effects of gender on outcome. Effects on brain natriuretic peptide, apnea-hypopnea index, oxygen desaturation-index, urine-catecholamines, blood lipids, C-reactive protein, glucose metabolism (S-glc, HBA1c), insulin resistance, serum creatinine, hemoglobin, daytime sleepiness (ESS, KSS), lung function (FVC, FEV1), airway inflammation (exhaled NO) Procedures: Sleep apnea investigation while patients are treated with CPAP for one night. Urinary samplings during the same night. They are also investigated with 24 h blood pressure measurements. Blood samples are taking fasting in the morning followed by measuring the arterial stiffness (Vicorder, Skidmore Medical UK) including pulse wave analysis using sphygmomanometer (Omron Japan). The same investigations are done at follow-up 5 days later where half of the patients have continued using CPAP treatment and half of them has slept without CPAP.

Detailed description: Patients fulfilling inclusion criteria are invited to the trial after informed consent for baseline and follow-up investigations.

Baseline investigations Day 1 Patients are given a questionnaire. They are given blood pressure monitoring, (ABPM Medical 90217 ambulatory blood pressure monitor, Spacelab) for 24 hours a starting at 8-9 AM. They are also given sleep apnea recorder (Embletta, X 10 system, Embla systems, ResMed) for ambulatory use during the following night, and a container for urinary sampling during the night (urine norepinephrine).

Day 2 Fasting on arrival. Return of the 24-h blood pressure recorder, the sleep apnea recorder and the urine sampling container.

Blood samples at 08.15 am after resting for 15 minutes. Arterial stiffness is measured using arterial pulse wave velocity, radial artery applanation tonometry and office blood pressure. After resting, the measurements starts at 8.30 AM in a room with a temperature of 24°C. Pulse wave velocity (Vicorder, Skidmore Medical, Bristol, UK) is measured in the supine position. The augmentation index is derived from pulse wave analysis obtained from radial artery applanation tonometry on the right arm (SphygmoCor, AtCor Medical, Sydney, Australia).

Lung function and exhaled NO measurements, ECG. Breakfast at around 10.00 am. CPAP time counter check Patients are then randomized with a ration of 1:1 to continue with CPAP or not for the following 5 nights.

Follow-up measurements Day 6 They are given blood pressure monitoring, (ABPM Medical 90217 ambulatory blood pressure monitor, Spacelab) for 24 hours a starting at 8-9 AM. They are also given sleep apnea recorder (Embletta, X 10 system, Embla systems, ResMed) for ambulatory use during the following night, and a container for urinary sampling during the night (urine norepinephrine).

Day 7 Fasting on arrival. CPAP time counter check Return of the 24-h blood pressure recorder, the sleep apnea recorder and the urine sampling container.

Blood samples at 08.15 am after resting for 15 minutes. Arterial stiffness is measured using arterial pulse wave velocity, radial artery applanation tonometry and office blood pressure. After resting, the measurements starts at 8.30 AM in a room with a temperature of 24°C. Pulse wave velocity (Vicorder, Skidmore Medical, Bristol, UK) is measured in the supine position. The augmentation index is derived from pulse wave analysis obtained from radial artery applanation tonometry on the right arm (SphygmoCor, AtCor Medical, Sydney, Australia).

Lung function and exhaled NO measurements, ECG. Breakfast at around 10.00 am. Trials ends and patients are told to continue with CPAP as usual.

Eligibility criteria: Inclusion Criteria:

* 18 years or older,
* given the written consent to participate in the study,
* 2 months to 2 years of continuous positive airway pressure (CPAP) treatments with good compliance (mean CPAP use of \>4 hours/night) during the last month before inclusion
* moderate sleep apnea with Apnea Hypopnea Index \>15 before treatment

Exclusion Criteria:

* Apnea hypopnea index \> 10 with CPAP treatment,
* heart infarction within 3 months prior to study participation,
* severe dementia,
* determined by study personal having psychological or physical hinder to participate in the study

Primary outcomes:
measure: Arterial stiffness.
timeFrame: 5 days
measure: Systolic and diastolic blood pressure
timeFrame: 5 days
Secondary outcomes:
measure: Gender differences
timeFrame: 5 days
measure: Effect on myocardial function
timeFrame: 5 days
measure: Impact on apnea hypopnea index
timeFrame: 5 days
measure: Effect on oxygen saturation
timeFrame: 5 days
measure: Effect on catecholamines
timeFrame: 5 days
measure: Effect on blood lipids in the form triglycerides
timeFrame: 5 days
measure: Effect on blood lipids in the form of cholesterol
timeFrame: 5 days
measure: Effect on systemic inflammation.
timeFrame: 5 days
measure: Effect on glucose metabolism in the form of fasting glucose
timeFrame: 5 days
measure: Long-term effect on glucose metabolism
timeFrame: 5 days
measure: Glucose metabolism in the form om Insulin levels
timeFrame: 5 days
measure: Effect on renal function
timeFrame: 5 days
measure: Effect on hemoglobin
timeFrame: 5 days
measure: Assessment of daytime sleepiness for a past period of time
timeFrame: 5 days
measure: Daytime sleepiness assessed at a certain time point
timeFrame: 5 days
measure: Effect on lung volumes
timeFrame: 5 days
measure: Effect on airway obstructions
timeFrame: 5 days
measure: Effect on airway inflammation
timeFrame: 5 days
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: Dept of Respiratory Medicine
Study officials:
affiliation: umea University
name: Karl A Franklin, Prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Umea University
name: Carin Sahlin, PhD
role: STUDY_DIRECTOR
References: