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NCT Number: NCT07409649

Influence of Intermittent Hypoxia on Loop Gain in Healthy Subjects

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.

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Key information

Conditions

Intermittent Hypoxia Healthy Volunteers

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Intermittent hypoxia

Procedure

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

Procedure

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 outcomes

  1. 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

    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

  1. 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

    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.

  2. 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

    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

  3. 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

    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).

  4. 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

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Celine ABONNEAU, Project manager

CONTACT

[email protected]

05 16 60 42 33 ext. +33

Vanessa BIRONNEAU, MD

CONTACT

[email protected]

05 49 44 34 49 ext. +33

Sponsors and collaborators

Lead sponsor

Poitiers University Hospital

Other

Registry information

Acronym: HI-LOOP

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Feb 13, 2026
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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