Clinical trial NCT03428516: Decrease Obstructive Sleep Apnea (OSA) Sympathetic Tone : Impact of APAP vs CPAP
Official title: Decrease in Sympathetic Tone in OSA Patients: Is CPAP More Effective Than APAP ?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Apnea Syndromes
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
name: ResMed
name: Agir pour les maladies chroniques
First posted: 2018-02-09
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Sympathetic tone (MSNA)
timeFrame: Change from baseline after one month of intervention
Secondary outcomes:
measure: 24 hours Systolic Blood pressure (AMBP)
timeFrame: Change from baseline after one month of intervention
measure: Systolic Blood pressure (office)
timeFrame: Change from baseline after one month of intervention
measure: Diastolic Blood pressure (office) change after 1 month
timeFrame: Change from baseline after one month of intervention
measure: Mean Blood pressure (office)
timeFrame: Change from baseline after one month of intervention
measure: Catecholamines (epinephrine)
timeFrame: Change from baseline after one month of intervention
measure: Norepinephrine)
timeFrame: Change from baseline after one month of intervention
measure: Dopamine (Catecholamine)
timeFrame: Change from baseline after one month of intervention
measure: High-frequency component of Heart rate variability
timeFrame: Change from baseline after one month of intervention
measure: Low frequency component of Heart rate variability
timeFrame: Change from baseline after one month of intervention
measure: 24 hours Diastolic blood pressure change (AMBP)
timeFrame: Change from baseline after one month of intervention
measure: 24 hours Mean Blood pressure (AMBP)
timeFrame: Change from baseline after one month of intervention
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU Grenoble Alpes
Study officials:
affiliation: University Grenoble Alps
name: Renaud Tamisier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.