Influence of Intermittent Hypoxia on Loop Gain in Healthy Subjects

Обзор

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.

Вмешательства

• Процедура 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
• Процедура 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.

Первичные конечные точки

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

Вторичные конечные точки (4)

• To compare the evolution of controller gain and plant gain between experimental conditions in hypoxia and ambient air [Срок оценки: through study completion (visit 1 and visit 2), an average of 14 months]
• To compare the change in the quantity of extracellular vesicles between experimental conditions in hypoxia and ambient air. [Срок оценки: through study completion (visit 1 and visit 2), an average of 14 months]
• 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. [Срок оценки: through study completion (visit 1 and visit 2), an average of 14 months]
• 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. [Срок оценки: through study completion (visit 1 and visit 2), an average of 14 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Франция · 1 центр

• Poitiers University Hospital — Poitiers

Идентификаторы

NCT: NCT07409649 · HI-LOOP · 2025-A02282-47

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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