Decrease Obstructive Sleep Apnea (OSA) Sympathetic Tone : Impact of APAP vs CPAP

Study Overview
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Brief Summary
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The present study aims to compare muscle sympathetic neural activity by microneurography after one month treatment of fixed versus auto-adjusting CPAP treatment and its impact on arterial blood pressure

Detailed Description
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Background: Sleep apnea syndrome (SAS) currently affects 10% of general population. It is characterized by the occurrence during the sleep of the upper airways closure which cause repeated asphyxia. It is a public health problem due to its cardiometabolic complications. Indeed, the absence of SAS treatment increases cardiovascular mortality by 12% at 10 years. The main physiopathological mechanism is the activation of cardiovascular sympathetic control (the short-term regulation of blood pressure which bring in the sympathetic nervous system) An exposure to intermittent chronic hypoxia (caused by SAS) bring an increased of muscle sympathetic nerve activity (MSNA) contributing to elevated blood pressure Continuous Positive Airway Pressure (CPAP) can partly reduce this risk by decreasing elevation of blood pressure caused by the SAS. It has recently been demonstrated that all CPAP devices are not equivalent. Indeed, the auto-adjusted CPAP treatment induces a reduction in blood pressure lower than the reference treatment fixed CPAP. To this extent it is interesting to conduct a new randomized trial comparing these two treatments with vascular sympathetic tone. This will be assessed by peroneal microneurography recording. Objective: Compare Muscle Sympathetic Neural Activity (MSNA) by microneurography after one month of fixed versus auto-adjusted CPAP treatment in OSA patients naive from pressure therapy Methods: Prospective study, single-site, randomized, double-blind, parallel, one month controlled trial. After the diagnosis of sleep apnea, patients will be randomized for one month treatment with fixed ou auto-adjusting CPAP. Measurements of MSNA, heart rate variability and catecholamines will be held before and after treatment. An interim analysis will be performed after the inclusion of 24 patients based on group sequential design

Official Title
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Decrease in Sympathetic Tone in OSA Patients: Is CPAP More Effective Than APAP ?

Conditions
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Sleep Apnea Syndromes

Intervention / Treatment
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* Device: Fixed CPAP
* Device: Auto-adjusting CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient with OSA (AHI ≥20 / h) patient with daytime sleepiness naive of any pressure treatment of OSA patient able to provide written informed consent not a vulnerable person or legally protected adult. Exclusion Criteria: pregnancy Person deprived of liberty or subject to a legal protection measure. Patient with serious heart failure (According to investigator judgment) patient with central sleep apnea index above 20% of AHI Patient with a significant intercurrent pathology that can influence the results. (According to investigator judgment).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fixed CPAP<br>CPAP always deliver air with the same pressure | Device: Fixed CPAP<br>* CPAP is a device that applies continous fixed positive pressure to the airways in order to keep them opened during sleep<br>|
| Active Comparator: Auto-adjusting CPAP<br>Auto-CPAP changes the pressure delivered depending on events detected at any time (apnea, hypopnea …) and applies the lowest pressure required to eliminate events. | Device: Auto-adjusting CPAP<br>* Auto-adjusting CPAP is a device that applies auto-adjusting continous positive pressure to the airways in order to keep them opened during sleep<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sympathetic tone (MSNA) | Change from Baseline Sympathetic tone at 1 months | Change from baseline after one month of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 hours Systolic Blood pressure (AMBP) | Change from Baseline in 24 hours ambulatory systolic blood pressure | Change from baseline after one month of intervention | 
| Systolic Blood pressure (office) | Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP) | Change from baseline after one month of intervention | 
| Diastolic Blood pressure (office) change after 1 month | Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP) | Change from baseline after one month of intervention | 
| Mean Blood pressure (office) | Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP) | Change from baseline after one month of intervention | 
| Catecholamines (epinephrine) | 24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA). | Change from baseline after one month of intervention | 
| Norepinephrine) | 24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA). | Change from baseline after one month of intervention | 
| Dopamine (Catecholamine) | 24h urine samples will be collected and acidified with acetic acid, stored at -20°C until analysis. Catecholamines (epinephrine, norepinephrine, and dopamine) will be measured in one milliliter of urine by high-performance liquid chromatography with electrochemical detection (Coularray Detector, ESA Dionex, Chelmsford, USA). | Change from baseline after one month of intervention | 
| High-frequency component of Heart rate variability | We will use these mathematical methods to analyze a signal over time: temporal analysis, Fourier transformation and wavelet transformation. High-frequency (HF) translates fluctuations in parasympathetic activity to cardiac destination, modulated by ventilatory characteristics (frequency, courant volume). | Change from baseline after one month of intervention | 
| Low frequency component of Heart rate variability | We will use these mathematical methods to analyze a signal over time: temporal analysis, Fourier transformation and wavelet transformation. Low frequency (LF) is classically considered to reflect the activity of the sympathetic system rather than the parasympathetic system. | Change from baseline after one month of intervention | 
| 24 hours Diastolic blood pressure change (AMBP) | ambulatory measurements over 24h | Change from baseline after one month of intervention | 
| 24 hours Mean Blood pressure (AMBP) | ambulatory measurements over 24h | Change from baseline after one month of intervention |