Clinical trial NCT02557412: Effect of Nasal CPAP on Lipid Profile in Patients With Dyslipidaemia and Sleep Apnea
Official title: Long-term Effect of Nasal Continuous Positive Airway Pressure on Lipid Profile in Patients With Dyslipidaemia and Mild-moderate Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Sleep Apnea
Dyslipidaemia
Lead sponsor: Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Principe de Asturias
First posted: 2015-09-23
Enrollment: 0
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: OBJECTIVES Main objective: To assess if six months of treatment with CPAP, associated with conventional treatment, improves the lipid profile of patients with dyslipidemia and mild-moderate apnea-hypopnea syndrome (OSA).

Secondary objectives:

* Determine the additional effect of CPAP on insulin resistance and dyslipidemia in patients with mild-moderate OSA.
* Assess the impact of CPAP treatment in reducing cardiovascular risk in patients with dyslipidemia and mild-moderate OSA.

DESIGN Randomized, parallel group, non-blind, controlled clinical trial with conventional treatment.

STUDY POPULATION 35-75 year old subjects, diagnosed with dyslipidemia in last six months and in stable treatment during the last month with diet, cholesterol lowering drug, and cholesterol LDL levels\> 100 mg / dl in the last two successive visits clinics.

Sample size. 38 patients who completed the test in each treatment arm.

TREATMENT

Patients will be randomized to one of the following treatment arms form:

1. hygiene and dietary recommendations.
2. lifestyle intervention (more strict and promotion of daily physical activity and dietary control).
3. Treatment with positive airway pressure (CPAP).

ENDPOINTS:

Efficacy endpoints.

* Primary endpoint: LDL-cholesterol.
* Total cholesterol, HDL-cholesterol, triglycerides and C-reactive protein high sensitivity (hsCRP).
* Systemic Biomarkers: inflammatory (IL-6, IL-8 and tumor necrosis factor (TNF)-α), oxidative stress (8-isoprostane), endothelial damage (endothelin, vascular cell adhesion molecule 1 (VCAM-1) and Intercellular Adhesion Molecule 1 (ICAM-1)), sympathetic activity (neuropeptide Y) and appetite-regulating hormones (leptin, orexin A / hypocretin-1 and ghrelin).
* Fasting glucose, glycated hemoglobin (HbA1c), fasting insulin and Homeostasis Model Assessment (HOMA) index and quantitative insulin sensitivity check index (QUICKI), thyroid-stimulating hormone (TSH).
* Clinical questionnaires: short-form (SF)-12, EuroQoL, Functional Outcomes of Sleep Questionnaire (FOSQ) and International physical activity questionnaire (IPAQ).

Security endpoints.

* Notification of clinical adverse events.
* Compliance with CPAP (average hours use per day).
* Epworth Sleepiness Questionnaire.
* Development of cardiovascular events.

Detailed description: OBJECTIVES

Main objective: To assess if six months of treatment with CPAP, associated with conventional treatment, improves the lipid profile of patients with dyslipidemia and mild-moderate apnea-hypopnea syndrome (OSA).

Secondary objectives:

* Determine the additional effect of CPAP on insulin resistance and dyslipidemia in patients with mild-moderate OSA.
* Assess the impact of CPAP treatment in reducing cardiovascular risk in patients with dyslipidemia and mild-moderate OSA.
* Analyze the impact of supplemental CPAP treatment on glycemic control and the concentration of hsCRP in patients with dyslipidemia and mild-moderate OSA.
* Establish the impact of supplemental CPAP treatment on quality of life related to health of patients with dyslipidemia and mild-moderate OSA.
* Evaluate the effect of CPAP on inflammatory cytokines, oxidative stress biomarkers, sympathetic tone and regulating hormones intake in patients with dyslipidemia and mild-moderate OSA.
* Correlate CPAP induced changes in lipid levels with the changes produced in the basal inflammatory response, oxidative stress, sympathetic activity and intake regulating hormones.
* Compare the effect of CPAP with promotion of daily physical activity on lipid profile in patients with dyslipidemia and mild-moderate OSA.
* Identify the subgroup of patients with uncontrolled dyslipidemia and mild-moderate OSA in wich six months of treatment with CPAP achieve a more pronounced reduction in blood lipids.

DESIGN Randomized, parallel group, non-blind, controlled clinical trial with conventional treatment.

STUDY POPULATION 35-75 year old subjects, diagnosed with dyslipidemia in last six months and in stable treatment during the last month with diet, cholesterol lowering drug, and cholesterol LDL levels\> 100 mg / dl in the last two successive visits clinics.

Sample size. 38 patients who completed the test in each treatment arm.

TREATMENT

Patients will be randomized to one of the following treatment arms form:

1. hygiene and dietary recommendations.
2. lifestyle intervention (more strict and promotion of daily physical activity and dietary control).
3. Treatment with positive airway pressure (CPAP).

ENDPOINTS Efficacy endpoints.

* Primary endpoint: LDL-cholesterol.
* Total cholesterol, HDL-cholesterol, triglycerides and C-reactive protein high sensitivity (hsCRP).
* Systemic Biomarkers: inflammatory (IL-6, IL-8 and TNF-α), oxidative stress (8-isoprostane), endothelial damage (endothelin, VCAM-1 and ICAM-1), sympathetic activity (neuropeptide Y) and appetite-regulating hormones (leptin, orexin A / hypocretin-1 and ghrelin).
* Fasting glucose, glycated hemoglobin (HbA1c), fasting insulin and HOMA and QUICKI indexes, TSH.
* Clinical questionnaires: SF-12, EuroQoL, FOSQ and IPAQ.

Security endpoints.

* Notification of clinical adverse events.
* Compliance with CPAP (average hours use per day).
* Epworth Sleepiness Questionnaire.
* Development of cardiovascular events.

STATISTICAL PROCEDURES Data will be expressed as mean ± standard deviation, median (interquartile range) or percent, depending on type and distribution. For comparison between groups, or t-Student test, or the Mann-Whitney U-test or chi-square test will be used, as appropriate. The relationships between variables will be analyzed by Pearson correlation and multiple linear regression.

The treatment effect will be evaluated by analysis of variance for repeated measures with post-hoc multiple comparisons, using the Bonferroni test. A model of multiple logistic regression will be applied to determine the variables associated with treatment response. P values will be considered statistically significant \<0.05.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of dyslipidemia: The existence of a previous clinical diagnostic of dyslipidemia associated with lipid-lowering therapy. It is also considered patients who have an altered analytical, using the following cutoffs: total cholesterol ≥ 200 mg / dl, triglycerides ≥ 180 mg / dl, HDL-cholesterol ≤ 40 mg / dl or LDL-cholesterol ≥ 150 mg / dl. Lipid-lowering treatment and diet, stable in the last month.
* A concentration of LDL-cholesterol above 100 mg / dl, in the month prior to inclusion.
* An apnea-hypopnea index between 5-30 h-1

Exclusion Criteria:

* Apnea-hypopnea index of less than 5 h-1 or greater than 30 h-1.
* Predominance of central apneas and hypopneas, defined as more than 25% of all respiratory events.
* Professional drivers, risk profession or respiratory failure (according to criteria of the clinical pathway for diagnosis and treatment of sleep-disordered breathing).
* Very excessive daytime sleepiness (Epworth Sleepiness Scale\> 18).
* Morbid obesity (BMI\> 40 kg / m2).
* Prior treatment with CPAP.

Primary outcomes:
measure: LDL-cholesterol
timeFrame: 6 months
Secondary outcomes:
measure: Lipid profile
timeFrame: 6 months
measure: Systemic biomarkers
timeFrame: 6 months
measure: Glycated hemoglobin
timeFrame: 6 months
measure: Insulin resistance
timeFrame: 6 months
measure: Health-related quality of life
timeFrame: 6 months
measure: Daily physical activity
timeFrame: 6 months
measure: Clinical adverse events
timeFrame: 6 months
measure: CPAP compliance
timeFrame: 6 months
measure: Sleepiness
timeFrame: 6 months
Other outcomes:
Locations:
city: Alcalá de Henares
country: Spain
facility: Hospital Universitario Príncipe de Asturias
state: Madrid
Study officials:
affiliation: Hospital Universitario La Paz, IdiPAZ
name: Francisco Garcia-Rio, MD
role: STUDY_DIRECTOR
References: