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

Not Applicable
Completed
Conditions
Sleep Apnea Syndromes
Interventions
Device: Fixed CPAP
Device: Auto-adjusting CPAP
Registration Number
NCT03428516
Lead Sponsor
University Hospital, Grenoble
Brief Summary

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

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.

Assuming an α error of 5%, a statistical power of 80%, and a unilateral situation : 34 patients per arm will be needed to be enrolled in the study. The enrollment target for the study will be reviewed and may be refined following the study interim analysis and taking account 20% of study drop-out.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
57
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fixed CPAPFixed CPAPCPAP always deliver air with the same pressure
Auto-adjusting CPAPAuto-adjusting CPAPAuto-CPAP changes the pressure delivered depending on events detected at any time (apnea, hypopnea ...) and applies the lowest pressure required to eliminate events.
Primary Outcome Measures
NameTimeMethod
Sympathetic tone (MSNA)Change from baseline after one month of intervention

Change from Baseline Sympathetic tone at 1 months

Secondary Outcome Measures
NameTimeMethod
24 hours Systolic Blood pressure (AMBP)Change from baseline after one month of intervention

Change from Baseline in 24 hours ambulatory systolic blood pressure

Mean Blood pressure (office)Change from baseline after one month of intervention

Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP)

Catecholamines (epinephrine)Change from baseline after one month of intervention

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 from ESA- Dionex, Chelmsford, USA).

Diastolic Blood pressure (office) change after 1 monthChange from baseline after one month of intervention

Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP)

24 hours Diastolic blood pressure change (AMBP)Change from baseline after one month of intervention

ambulatory measurements over 24h

Systolic Blood pressure (office)Change from baseline after one month of intervention

Clinical BP on 3 occasions, SBP and BP will be assessed. Mean BP calculated as DBP+1/3(SBP-DBP)

Norepinephrine)Change from baseline after one month of intervention

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 from ESA- Dionex, Chelmsford, USA).

High-frequency component of Heart rate variabilityChange from baseline after one month of intervention

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).

Dopamine (Catecholamine)Change from baseline after one month of intervention

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 from ESA- Dionex, Chelmsford, USA).

24 hours Mean Blood pressure (AMBP)Change from baseline after one month of intervention

ambulatory measurements over 24h

Low frequency component of Heart rate variabilityChange from baseline after one month of intervention

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.

Trial Locations

Locations (1)

CHU Grenoble Alpes

🇫🇷

Grenoble, France

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