Influence of Intermittent Hypoxia on Loop Gain in Healthy Subjects

Overview

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

• Procedure 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
• Procedure 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.

Primary outcome measures

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

Secondary outcome measures (4)

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

Eligibility criteria

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

Exclusion 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Prevention

Study locations

France · 1 center

• Poitiers University Hospital — Poitiers

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗