Normotensive OSA Patients With Dipper Circadian Blood Pressure Pattern

Study Overview
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Brief Summary
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The principal objective is to evaluate the effect of CPAP treatment on blood pressure (BP) in normotensive patients with dipper circadian pattern with sleep apnea-hypopnea syndrome (SAHS). The secondary objectives are: i) To evaluate the prevalence of the different circadian patterns of BP in ambulatory blood pressure monitoring (ABPM) ii) To establish the relationship between CPAP compliance and BP response; iii) Identify which ABPM variables and biomarkers are related to BP response; iv) Evaluate changes in the biomarkers' profile with the CPAP treatment. Methodology: Open-label, parallel, prospective, randomized and controlled trial including normotensive patients diagnosed with severe SAHS without significant somnolence. 64 patients with dipper circadian pattern will be included and will be randomized to receive CPAP (32) or conservative treatment (32). ABPM and blood sample collection will be performed at the beginning of the study and at 3 months.

Detailed Description
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Recruitment: Normotensive subjects referred to the sleep unit of the Hospital Santa Maria (Spain) who are diagnosed of severe OSA (AHI≥30) by a sleep study and dipper circadian blood pattern confirmed by ABPM and who do not present significant somnolence (Epworth≤18) will be included in the study. Definition of the groups: Patients will be randomized to receive one of the following treatments: CPAP: Patients who will receive CPAP treatment. The CPAP titration will be carried out with an automatic or manual CPAP according to usual clinical practice. Conservative treatment: Patients who will receive conservative treatment based on hygienic-dietetic measures. Randomization: It will be carried out with an automated platform Duration of the treatment: All patients randomized to CPAP will begin treatment as soon as possible after randomization, and will continue treatment until the study ends (3 months). Patients who interrupt treatment will be excluded from the study. ABPM and blood sample collection will be performed on all included patients at the beginning of the study and at 3 months under treatment (CPAP or conservative care). Follow-up: All patients will be evaluated at the beginning of the study (T0), at first month (T1) and at three months (T2), during the follow-up period.

Official Title
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CPAP Effect in Nocturnal Blood Pressure in Normotensive Patients With Dipper Circadian Pattern and Severe Obstructive Sleep Apnea (OSA)

Conditions
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Normotensive, Sleep Apnea, Obstructive

Intervention / Treatment
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* Device: CPAP treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over 18 years of age Referred to the sleep unit for suspected OSA Being normotensive and presenting an AHI ≥ 30 in the sleep study Signature of the informed consent. Exclusion Criteria: Previous CPAP treatment Significant somnolence defined by an Epworth Sleepiness Scale (ESS) score higher than 18 Psychophysical inability to complete questionnaires Previous diagnosis or suspicion of another sleep disorder Presence of more than 50% of central apneas or Cheyne-Stokes respiration Having a serious chronic disease: neoplasia, renal failure, severe chronic obstructive pulmonary disease, chronic depression and other chronic limiting diseases Medical history that may interfere with the objectives of the study or, in the opinion of the researcher, may compromise the conclusions Any medical, social or geographical factor that may endanger the patient's compliance 9-Having a profession of high risk (professional driver).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open-label, parallel, prospective, randomized and controlled trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPAP treatment<br>Group of patients who will receive CPAP treatment | Device: CPAP treatment<br>* In this group of patients (CPAP group) will be prescribed CPAP treatment at an optimal pressure. It will be performed a CPAP titration with an automatic or manual CPAP according to usual clinical practice.<br>|
| No Intervention: Conservative measures<br>Patients who will receive conservative treatment based on hygienic-dietetic measures | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of CPAP treatment on BP according to the circadian BP pattern in normotensive dipper patients with severe OSA | Change in mmHg in the blood pressure of the ambulatory blood pressure monitoring parameters after the treatment | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of the different circadian BP patterns (dipper/no-dipper) in the ABPM of normotensive subjects diagnosed with severe OSA without significant somnolence (Epworth≤18) | The prevalence of each circadian patterns will be calculated from the baseline ambulatory blood pressure monitoring data | 3 years | 
| Relationship between compliance with CPAP treatment and the blood pressure change in these patients | The relation between CPAP compliance (mean hours per night) and change in mean nighttime BP using multivariate models in patients randomized to CPAP treatment. | 3 years | 
| Ambulatory blood pressure parameters different to circadian blood pressure that are related to the response to CPAP treatment | Using all the ABPM variables we will proceed to the identification of variables that are related to the change in mean nocturnal BP in patients treated with CPAP. | 3 years | 
| Changes in the biomarkers' profile after CPAP treatment | Using the the blood samples obtained in the baseline and 3 months visit it will be evaluated possible changes in the biomarkers profile after CPAP treatment. Learning Phase: complete profile analysis (754 miRNAs) will be carried out in 24 patients Learning Phase: complete profile analysis (754 miRNAs) will be carried out in 24 patients representative of the change in BP in treated patients. The miRNAs associated with the change in BP will be identified from the 754 miRNAs potentially present in serum and plasma. Validation Phase: Specific primers will be designed for the real-time PCR amplification of the genes for which we have found a significant association The miRNAs found will be analyzed after 3 months of treatment. Analysis of biomarkers. Immunoassay techniques will evaluate the following markers before and after treatment: angiotensin I, II and III, plasma renin activity, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and endogenous ouabain. | 3 years |