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出境医 / 临床实验 / Pathophysiological Study of CSA in Adults With pLVEF (PHENOSAX)
Pathophysiological Study of CSA in Adults With pLVEF (PHENOSAX)
Study Description
Brief Summary:
Sleep apnea is classically divided into obstructive and central apnea, according to the persistence or otherwise of respiratory movements and the existence or not of pharyngeal collapse during apnea. However, there is evidence to suggest that some mechanisms are common to both types of apnea. Although the pathophysiology of obstructive apnea has been the subject of much work and now seems fairly well known, there is much less data on central apnea. These apneas can occur in different comorbid contexts. They are more frequently present in patients with heart failure, regardless of the etiology, and are associated with an adverse prognosis. The investigators hypothesize that the physiopathology of adult central apnea syndrome involves, in addition to ventilatory control abnormalities, upper airway abnormalities (VAS). The objective is to study the pathophysiology of central SAS, by first comparing the collapse of VAS of central apneic patients to those of patients with simple snoring or obstructive sleep apnea. In a second step, the investigators will analyze the cardiorespiratory coupling and will establish a map of the respiratory neural network in patients with central apnea. The investigators will focus their study on patients with central SAS (with preserved systolic heart function) due to the epidemiology of SAS.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Central Sleep Apnea | Other: Critical airway closure pressure (Pcrit) measurment Other: Acoustic pharyngometry Other: High density surface electroencephalogram neural mapping | Not Applicable |
Detailed Description:
A non-randomized case-control comparative monocentric physiopathology study with 3 parallel groups (one group of cases and two control groups) matched for age and body mass index (individual 1: 1: 1 match), to evaluate changes in the collapse of VAS in central apnea ("central SAS case"), compared to subjects without central apnea ("obstructive SAS" and "single snoring").
Primary objective : Evaluation of changes in upper airway collapse in patients with central sleep apnea syndrome with preserved LVEF heart failure ("central SAS case"), compared with snoring subjects free from sleep apnea syndrome ("Simple snoring witnesses")
Secondary objectives :
- Study the collapsibility of VAS according to the type of apnea ("central SAS case" versus "obstructive SAS case").
- To study the association between the collapsibility of VAS and the global and central apnea-hypopnoea index (IAH).
- Study the association between the type of disorder ("central SAS case" versus "simple snoring controls", "central SAS case" versus "obstructive SAS controls") and cardiorespiratory coupling.
- Study the association between the type of disorder ("central SAS case" versus "simple snoring controls", "central SAS case" versus "obstructive SAS controls") and the CO2 response slope.
- Establish a map of the respiratory neural network in patients with central SAS with preserved ejection fraction.
- Study the association between the volumes in acoustic pharyngometry and the values of the Pcrit
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 45 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Other |
| Official Title: | Pathophysiological Study of Central Sleep Apnea in Adults With Preserved LVEF |
| Actual Study Start Date : | February 2, 2021 |
| Estimated Primary Completion Date : | February 2, 2024 |
| Estimated Study Completion Date : | February 2, 2025 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Central SAS cases
Patients with central apnea
|
Other: Critical airway closure pressure (Pcrit) measurment
Pcrit is measured in awake patient, by applying a gradually decreasing pressure through a nasal NIV mask. Pcrit is defined as the pressure inducing airflow cessation in upper airway
Other: Acoustic pharyngometry Acoustic pharyngometry will assess the volume of the pharynx and determine if there is an obstacle in the upper airways.
Other: High density surface electroencephalogram neural mapping Mapping of the respiratory neural network will allow us to study the areas of the brain activated during breathing
|
|
Obstructive SAS controls
Patients with moderate to severe obstructive apnea (apnea-hypopnoea index ≥ 15 / h)
|
Other: Critical airway closure pressure (Pcrit) measurment
Pcrit is measured in awake patient, by applying a gradually decreasing pressure through a nasal NIV mask. Pcrit is defined as the pressure inducing airflow cessation in upper airway
Other: Acoustic pharyngometry Acoustic pharyngometry will assess the volume of the pharynx and determine if there is an obstacle in the upper airways.
|
|
Snorers controls
Snorers controls : Patients with snoring, with or without mild obstructive apneas (index of apnea-hypopneas <15 / h)
|
Other: Critical airway closure pressure (Pcrit) measurment
Pcrit is measured in awake patient, by applying a gradually decreasing pressure through a nasal NIV mask. Pcrit is defined as the pressure inducing airflow cessation in upper airway
Other: Acoustic pharyngometry Acoustic pharyngometry will assess the volume of the pharynx and determine if there is an obstacle in the upper airways.
|
Outcome Measures
Primary Outcome Measures :
- Upper airway collapsibility is assessed by Pcrit value in central leep apnea and snoring [ Time Frame: 1 day ]Pressure values of VAS (Pcrit) in patients in the "Central SAS" group and in the "Obstructive SAS" group
Secondary Outcome Measures :
- Upper airway collapsibility is assessed by Pcrit value in central and obstructive sleep apnea [ Time Frame: 1 day ]Pcrit value in cm H20 in the obstructive SAS group vs. central SAS group
- The association between Pcrit (cm H20) and Apnea-Hypopnoea Index (events/h) [ Time Frame: 1 day ]The association between Pcrit (cm H20) and Global and Central Apnea-Hypopnoea Index (events/h)
- Chemosensitivity in central sleep apnea is assessed by CO2 response test [ Time Frame: 1 day ]CO2 response slope (mL/min/mmHg) in CO2 response test via rebrething method
- Cardiorespiratory coupling in central sleep apnea is assessed by RR measurment (mm on EKG) [ Time Frame: 1 day ]Parameters of cardiorespiratory coupling to polysomnography
- Neural network modifications in sleep apnea are assessed by frequency couplage indice [ Time Frame: 1 day ]Respiratory neural network mapping in patients with central SAS with preserved ejection fraction through high density mapping
- Volume and collapsibility characteristics in acoustic pharyngometry in the different groups [ Time Frame: 1 day ]
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male patient
- Age ≥18 years and ≤85 years
- With preserved LVEF heart failure (defined as LVEF ≥ 45% on ultrasound, MRI or isotopic ventriculography)
- Central SAS Group: Central to severe sleep apnea syndrome, defined by an apnea-hypopnoea index (IAH) greater than 15 per hour, of which at least 30% are central events;
- Obstructive SAS group: Moderate to severe obstructive sleep apnea syndrome, defined by an apnea-hypopnoea index (IAH) greater than 15 per hour, with a central event proportion of less than 30%
- Group "snoring": absence of sleep apnea syndrome or mild sleep apnea syndrome (IAH <15 / h) in polysomnography, and presence of snoring on at least 30% of the night of recording.
- Free, informed and written consent
- Patient affiliated to a social security scheme (beneficiary or beneficiary)
Exclusion Criteria:
- Impossibility of giving the subject informed information
- Participation in a research protocol involving the human person in the previous months if an exclusion directive is given in this protocol
- Use of respiratory or sedative depressant drugs, systemic corticosteroid therapy
- Impaired systolic function (defined by LVEF <45% in ultrasound, MRI or isotopic ventriculography)
- Unstable cardiovascular disease (cardiovascular event of less than one month)
- Recent surgery of the ENT sphere (less than 6 months)
- Central neurological pathology known
- Known, severe respiratory pathology (severity left to the investigator's discretion)
- Renal insufficiency (creatinine clearance <60 mL / min) or severe hepatic impairment
- Primary or secondary hemostasis disorder
- Patient on anticoagulant (antivitamin K, direct oral anticoagulant, heparin and related). Antiplatelet agents are allowed.
- Psychiatric pathology according to DSM-V criteria, unbalanced
- Pulsed saturation with oxyhemoglobin <88% at rest, on awakening
- Allergy to lidocaine
- Patient under tutorship or curatorship
- Failure to perform a prior medical examination
- Tympanic perforation
Contacts and Locations
Contacts
| Contact: Marie-Pia D'ORTHO, Professor | (33) 01 40 25 84 01 | marie-pia.dortho@aphp.fr | |
| Contact: Justine FRIJA MASSON, Doctor | (33) 01 40 25 84 01 | justine.frija@aphp.fr |
Locations
| France | |
| Hôpital Bichat-Claude Bernard | Recruiting |
| Paris, France, 75018 | |
| Contact: Marie-Pia D'ORTHO, Professor (33) 01 40 25 84 01 marie-pia.dortho@aphp.fr | |
| Contact: Justine FRIJA MASSON, Doctor (33) 01 40 25 84 01 justine.frija@aphp.fr | |
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
| Principal Investigator: | Marie-Pia D'ORTHO, Professor | Assistance Publique - Hôpitaux de Paris |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | March 12, 2019 | ||||||||
| First Posted Date ICMJE | April 18, 2019 | ||||||||
| Last Update Posted Date | March 23, 2021 | ||||||||
| Actual Study Start Date ICMJE | February 2, 2021 | ||||||||
| Estimated Primary Completion Date | February 2, 2024 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Upper airway collapsibility is assessed by Pcrit value in central leep apnea and snoring [ Time Frame: 1 day ] Pressure values of VAS (Pcrit) in patients in the "Central SAS" group and in the "Obstructive SAS" group
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Pathophysiological Study of CSA in Adults With pLVEF | ||||||||
| Official Title ICMJE | Pathophysiological Study of Central Sleep Apnea in Adults With Preserved LVEF | ||||||||
| Brief Summary | Sleep apnea is classically divided into obstructive and central apnea, according to the persistence or otherwise of respiratory movements and the existence or not of pharyngeal collapse during apnea. However, there is evidence to suggest that some mechanisms are common to both types of apnea. Although the pathophysiology of obstructive apnea has been the subject of much work and now seems fairly well known, there is much less data on central apnea. These apneas can occur in different comorbid contexts. They are more frequently present in patients with heart failure, regardless of the etiology, and are associated with an adverse prognosis. The investigators hypothesize that the physiopathology of adult central apnea syndrome involves, in addition to ventilatory control abnormalities, upper airway abnormalities (VAS). The objective is to study the pathophysiology of central SAS, by first comparing the collapse of VAS of central apneic patients to those of patients with simple snoring or obstructive sleep apnea. In a second step, the investigators will analyze the cardiorespiratory coupling and will establish a map of the respiratory neural network in patients with central apnea. The investigators will focus their study on patients with central SAS (with preserved systolic heart function) due to the epidemiology of SAS. | ||||||||
| Detailed Description |
A non-randomized case-control comparative monocentric physiopathology study with 3 parallel groups (one group of cases and two control groups) matched for age and body mass index (individual 1: 1: 1 match), to evaluate changes in the collapse of VAS in central apnea ("central SAS case"), compared to subjects without central apnea ("obstructive SAS" and "single snoring"). Primary objective : Evaluation of changes in upper airway collapse in patients with central sleep apnea syndrome with preserved LVEF heart failure ("central SAS case"), compared with snoring subjects free from sleep apnea syndrome ("Simple snoring witnesses") Secondary objectives :
|
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| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Not Applicable | ||||||||
| Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Other |
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| Condition ICMJE | Central Sleep Apnea | ||||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
45 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | February 2, 2025 | ||||||||
| Estimated Primary Completion Date | February 2, 2024 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 85 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | France | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03919344 | ||||||||
| Other Study ID Numbers ICMJE | APHP 180442 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Assistance Publique - Hôpitaux de Paris | ||||||||
| Study Sponsor ICMJE | Assistance Publique - Hôpitaux de Paris | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE |
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| PRS Account | Assistance Publique - Hôpitaux de Paris | ||||||||
| Verification Date | March 2021 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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