About this trial
Sleep apnoea-hypopnoea syndrome (SAHOS), which causes numerous comorbidities, particularly cardiovascular ones, is widespread worldwide today and incurs significant healthcare costs.
Current research in this field focuses on identifying different phenotypes in affected patients in order to provide more personalised treatment.
One of these phenotypes appears to be linked to instability in ventilatory control due to an increase in loop gain (LG) in these subjects.
However, the pathophysiology of this ventilatory control instability due to increased LG is not fully understood. It is still difficult to determine whether subjects have an intrinsically high LG or if exposure to intermittent hypoxia during OSA promotes an increase in LG.
It has also been demonstrated that OSA causes vascular hyperreactivity by increasing oxidative stress through elevated ROS production. This leads to endothelial dysfunction in response to intermittent hypoxia associated with apnoea. Extracellular vesicles (microvesicles and exosomes) have been shown to play a role in this endothelial response. These extracellular vesicles are essential for intercellular communication in both physiological and pathological situations, such as SAHOS.
Therefore, the objective of this research is to determine whether exposure to intermittent hypoxia and changes in microvesicle phenotype could influence LG, which could lead to new therapeutic advances in the context of SAHOS.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy subjects aged 18 to 45
BMI between [18-25] kg/m2
No known sleep disorders
Free subjects, not under guardianship or curatorship or subordination
Disqualifiers
Active smoking or cessation within the last 3 months and total consumption > 10 pack-years
Alcohol or drug addiction
Excessive coffee consumption (> 3 espressos/day)
History of acute mountain sickness (presence of symptoms such as dizziness, headaches, nausea/vomiting, and incapacitating fatigue during or after a stay at high altitude)
Trial design
Crossover
Treatments tested in this trial
Intermittent hypoxia
Procedure/SurgeryThe volunteer will remain at rest in the hypoxic chamber, experiencing intermittent hypoxic conditions cyclically every 6 minutes. During one third of the cycle, they will be exposed to hypoxia in order to reduce SpO₂ to between 85% and 90%. Then, during two thirds of the cycle, they will receive oxygenation at a rate of 1 L/min (with possible subject-dependent modulations), with the aim of achieving an SpO₂ of greater than 95%. To make the hypoxia intermittent, the volunteer will also be given a medium-concentration oxygen mask that provides intermittent airflow, controlled by the D-6341 mass flow controller.
Normoxia
Procedure/SurgeryThe participant will remain at rest in the hypoxic chamber under normoxic conditions. To prevent the volunteer from becoming aware of the conditions to which they are exposed, an air flow rate of 1 L/min will be used to simulate intermittent oxygenation.
Treatment groups
Trial outcomes
Primary outcomes
To evaluate the effect of intermittent hypoxia for 6 hours on the evolution of Loop Gain
Loop gain is the product of 'controller gain' (ventilatory responsiveness to CO₂ above eupnoea) and 'plant gain' (the ventilatory increase required for a given reduction in PaCO₂). Loop gain will be measured before (30 minutes of rest following the participant's arrival) and after (20 minutes before the end of the hypoxia chamber session) the test or control condition (intermittent hypoxia or ambient air). The following ventilatory parameters will be measured using a gas exchange measuring device to calculate loop gain, plant gain and controller gain: * PETCO₂ in mmHg * PETO₂ in mmHg * Minute ventilation (VE), measured in mL/min (tidal volume x respiratory rate). The focus will be on the average loop gain value measured over spontaneous breathing cycles of five to ten minutes. The evaluation criterion will be the difference in the average loop gain value before and after the experimental conditioning (i.e. observation of the change).
Secondary outcomes
To compare the evolution of controller gain and plant gain between experimental conditions in hypoxia and ambient air
We will assess the change in controller and plant gains by measuring the difference before and after the experimental conditioning of these gains. Our focus will be on the average values of the controller and plant gains, which were measured over spontaneous breathing cycles of 5 to 10 minutes, and assessed before and after the experiment.
To compare the change in the quantity of extracellular vesicles between experimental conditions in hypoxia and ambient air.
The quantity of extracellular vesicles was assessed from blood samples using flow cytometry with specific antibodies. This change is expressed as the difference in the following extracellular vesicle concentrations before and after experimental conditioning: * EVs from platelets expressing CD41 * EVs from erythrocytes expressing CD235a * EVs from leukocytes expressing CD45 * EVs from endothelial cells expressing CD146 * EVs from granulocytes expressing CD66b and CD11b * EVs from activated leukocytes expressing CD62L * EVs from activated endothelial cells expressing CD62E * EVs from activated platelets expressing CD62P * CD62P/platelet ratio * EVs carrying the PSGL-1 ligand expressing CD162 * EVs carrying phosphatidylserine expressing annexin V
To assess whether changes in the quantity of extracellular vesicles (and microvesicles) correlate with changes in loop gain, both under experimental conditions in hypoxia and under experimental conditions in ambient air.
We are interested in changes in the quantity of extracellular vesicles, as assessed by the difference in extracellular vesicle concentration before and after the experimental condition. This is measured from blood samples taken. We are interested in the following extracellular vesicles: CD41, CD235a, CD45, CD146, CD66b, CD11b, CD62L, CD62E, CD62P and CD62/platelet annexin V. The change in loop gain will be calculated as for the primary endpoint (the difference in concentration before and after the experimental condition).
To compare changes in loop gain between experimental conditions in hypoxia and ambient air, on the one hand in the subgroup of patients with hyperventilation syndrome and on the other hand in the subgroup of patients without hyperventilation syndrome.
The change in loop gain will be defined in the same way as the primary endpoint, i.e. as the difference between the measurements taken before and after the experimental conditioning. Hyperventilation syndrome will be defined as a Nijmegen score of 23 or above at the inclusion visit.
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