CClinicalTrials.gg
CompletedNCT03428516APAP-CPAPUpdated May 16, 2024

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

An interventional study of Fixed CPAP and Auto-adjusting CPAP in Sleep Apnea Syndromes, sponsored by University Hospital, Grenoble. Completed at 1 site in France. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-05-16.

Sponsored by University Hospital, Grenoble · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
57
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Sleep Apnea Syndromes
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
04

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
57 participants (actual)

Study arms

  • Experimental
    Fixed CPAP

    CPAP always deliver air with the same pressure

    Device: Fixed CPAP

  • 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

Interventions

  • DeviceFixed CPAP

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

  • DeviceAuto-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

05

What researchers measure

Primary outcomes

  1. Sympathetic tone (MSNA)

    Change from Baseline Sympathetic tone at 1 months

    Time frame: Change from baseline after one month of intervention

Secondary outcomes

  1. 24 hours Systolic Blood pressure (AMBP)

    Change from Baseline in 24 hours ambulatory systolic blood pressure

    Time frame: Change from baseline after one month of intervention

  2. Systolic Blood pressure (office)

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

    Time frame: Change from baseline after one month of intervention

  3. 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)

    Time frame: Change from baseline after one month of intervention

  4. Mean Blood pressure (office)

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

    Time frame: Change from baseline after one month of intervention

  5. 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).

    Time frame: Change from baseline after one month of intervention

  6. 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).

    Time frame: Change from baseline after one month of intervention

  7. 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).

    Time frame: Change from baseline after one month of intervention

  8. 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).

    Time frame: Change from baseline after one month of intervention

  9. 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.

    Time frame: Change from baseline after one month of intervention

  10. 24 hours Diastolic blood pressure change (AMBP)

    ambulatory measurements over 24h

    Time frame: Change from baseline after one month of intervention

  11. 24 hours Mean Blood pressure (AMBP)

    ambulatory measurements over 24h

    Time frame: Change from baseline after one month of intervention

06

Study locations

1 site
  • CHU Grenoble Alpes
    Grenoble, 38000, France
07

References and documents

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. PubMed 27091542 ↗
  • 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. PubMed 30948567 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03428516
Lead sponsor
University Hospital, Grenoble
Collaborators
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., ResMed, Agir pour les maladies chroniques
Responsible party
Sponsor
First posted
Feb 9, 2018
Start date
Mar 1, 2018
Primary completion
Nov 17, 2022
Completion
Nov 30, 2022
Last update
May 16, 2024

Study contacts

Renaud Tamisier, MD, PhD
principal investigator · University Grenoble Alps

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion