Influence of Intermittent Hypoxia on Loop Gain in Healthy Subjects

Condition(s) studied

Investigational drug(s) / intervention(s)

Intermittent hypoxia: The 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: The 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.

Study summary

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

Primary outcome measure(s)

• To evaluate the effect of intermittent hypoxia for 6 hours on the evolution of Loop Gain — through study completion (visit 1 and visit 2), an average of 14 months
  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).

Trial sites (1)

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