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

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

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

Study Overview

• Status: Completed
• Conditions: Sleep Apnea Syndromes
• Intervention / Treatment: Device: Fixed CPAP; Device: Auto-adjusting CPAP

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38000
    • Chu Grenoble Alpes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fixed CPAP; CPAP always deliver air with the same pressure	Device: Fixed CPAP; CPAP is a device that applies continous fixed positive pressure to the airways in order to keep them opened during sleep
Active Comparator: Auto-adjusting CPAP; 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; Auto-adjusting CPAP is a device that applies auto-adjusting continous positive pressure to the airways in order to keep them opened during sleep

What is the study measuring?

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
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
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 from 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 from 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 from ESA- Dionex, Chelmsford, USA).	Change from baseline after one month of intervention

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.; ResMed; Agir pour les maladies chroniques
• Investigators: Principal Investigator: Renaud Tamisier, MD, PhD, University Grenoble Alps

Publications and helpful links

General Publications

• Pepin JL, Tamisier R, Baguet JP, Lepaulle B, Arbib F, Arnol N, Timsit JF, Levy P. Fixed-pressure CPAP versus auto-adjusting CPAP: comparison of efficacy on blood pressure in obstructive sleep apnoea, a randomised clinical trial. Thorax. 2016 Aug;71(8):726-33. doi: 10.1136/thoraxjnl-2015-207700. Epub 2016 Apr 18.
• Treptow E, Pepin JL, Bailly S, Levy P, Bosc C, Destors M, Woehrle H, Tamisier R. Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol. BMJ Open. 2019 Apr 4;9(4):e024253. doi: 10.1136/bmjopen-2018-024253.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): November 17, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes
• Other Study ID Numbers: 2017-A02937-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No