Intermittent Hypoxia, Healthy Volunteers
Conditions
Keywords
loop gain
Brief 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.
Interventions
PROCEDUREIntermittent 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.
PROCEDURENormoxia
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.
Sponsors
Poitiers University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 * Persons affiliated with or beneficiaries of a Social Security scheme * Signature of informed consent after clear and honest information about the study Non-inclusion Criteria: * 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) * Living at high altitude (above 3,000 meters, continuously for more than 6 months during the last 10 years) * History of respiratory and/or cardiovascular and/or renal and/or neurological disease (migraines, epilepsy) * Diabetes * Anemia, sickle cell anemia * Any medication associated with oxygen metabolism and any psychotropic medication (anxiolytics, sedatives, antidepressants, neuroleptics, muscle relaxants, etc.) that may interfere with motor and respiratory control, muscle strength, or sleep quality * Women of childbearing age who do not use effective contraception (hormonal/mechanical: oral, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total ovariectomy) * Concurrent participation in another clinical research study affecting respiratory control or respiratory muscles * Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by judicial or administrative decision, persons staying in a healthcare facility Post-inclusion
Exclusion criteria
* SpO2 \< 97% in ambient air at rest. * Detection of pregnancy in women of childbearing age. * Detection of acute mountain sickness (Lake Louise score \> 0). * Abnormalities in spirometry, ventilatory polygraphy, electrocardiogram, and/or hemoglobinometry prior to randomization. * Ventilation minute signal, PETCO2 or PETO2 unusable. * Irreversible deterioration in the volunteer's health during the study period, likely to affect the experimental conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in Loop Gain before and after 6 hours of experimental condition (intermittent hypoxia or ambient air). | after 6 hours of experimental condition | 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). 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) and Minute ventilation (VE) measured in mL/min (tidal volume x respiratory rate). For each experimental condition (test-hypoxia or control-ambient air), loop gain will be measured before the experimental condition (after 30 minutes of rest) and after the experimental condition (20 minutes before leaving the hypoxic chamber). The change in loop gain is defined as the difference between the average values (over 5 minutes) of the loop gain before and after the experimentation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change in controller gain before and after 6 hours of experimental condition (intermittent hypoxia or ambient air) | after 6 hours of experimental condition | 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) and Minute ventilation (VE) measured in mL/min (tidal volume x respiratory rate). For each experimental condition (test-hypoxia or control-ambient air), controller gain will be assessed before the experimental condition (after 30 minutes of rest) and after the experimental condition (20 minutes before leaving the hypoxic chamber). The change in controller gain is defined as the difference between the average values (over 5 minutes) of the controller gain before and after experimental condition. |
| The change in plant gain before and after 6 hours of experimental condition (intermittent hypoxia or ambient air) | after 6 hours of experimental condition | 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) and Minute ventilation (VE) measured in mL/min (tidal volume x respiratory rate). For each experimental condition (test-hypoxia or control-ambient air), plant gain will be assessed before the experimental condition (after 30 minutes of rest) and after the experimental condition (20 minutes before leaving the hypoxic chamber). The change in plant gain is defined as the difference between the average values (over 5 minutes) of the plant gain before and after experimental condition. |
| The change in the quantity of extracellular vesicles before and after 6 hours of experimental condition (intermittent hypoxia versus ambient air) | after 6 hours of experimental condition | The quantity of extracellular vesicles is assessed from blood samples using flow cytometry with specific antibodies. Blood samples are collected before the experimental condition (after 30 minutes of rest) and after the experimental condition (after leaving the hypoxic chamber). 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 |
| Correlation between the change in quantity of extracellular vesicles and change in loop gain | after 6 hours of experimental condition | The change in the quantity of extracellular vesicles is defined as the difference of the extracellular vesicle concentration before and after the experimental condition (intermittent hypoxia and ambient air). The change in loop gain is defined as the difference of the loop gain values before and after the experimental condition (same definition as the primary outcome). We are interested in the following extracellular vesicles: CD41, CD235a, CD45, CD146, CD66b, CD11b, CD62L, CD62E, CD62P and CD62/platelet annexin V. |
| Change in loop gain before and after experimental condition (intermittent hypoxia or ambient air), in the subgroup of patients with hyperventilation syndrome and in the subgroup of patients without hyperventilation syndrome. | after 6 hours of experimental condition | The change in loop gain is defined in the same way as the primary endpoint, i.e. as the difference between the measurements taken before and after the experimental condition. Hyperventilation syndrome is defined as a Nijmegen score of 23 or above at the inclusion visit. |
Countries
France
Contacts
CONTACTVanessa BIRONNEAU, MD
CONTACTCeline ABONNEAU, Project manager
Outcome results
None listed