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

Sleep Apnea Syndromes Clinical Trial

— APAP-CPAP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03428516
• Other study ID #: 2017-A02937-46
• Status: Completed
• Phase: N/A
• Start date: March 1, 2018
• Est. completion date: November 30, 2022

Study information

• Verified date: July 2022
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: November 30, 2022
• Est. primary completion date: November 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Sleep Apnea Syndromes

Intervention

Device:
• Fixed CPAP
CPAP is a device that applies continous fixed positive pressure to the airways in order to keep them opened during sleep
• 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

Locations

Country	Name	City	State
France	CHU Grenoble Alpes	Grenoble

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Agir pour les maladies chroniques, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., ResMed

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sympathetic tone (MSNA)	Change from Baseline Sympathetic tone at 1 months	Change from baseline after one month of intervention
Secondary	24 hours Systolic Blood pressure (AMBP)	Change from Baseline in 24 hours ambulatory systolic blood pressure	Change from baseline after one month of intervention
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	24 hours Diastolic blood pressure change (AMBP)	ambulatory measurements over 24h	Change from baseline after one month of intervention
Secondary	24 hours Mean Blood pressure (AMBP)	ambulatory measurements over 24h	Change from baseline after one month of intervention