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Cardio-respiratory Responses During Hypoxic Exercise in Individuals Born Prematurely

Not Applicable
Conditions
Hypoxia
Tolerance
Altitude Sickness
Interventions
Other: Graded exercise testing
Other: Resting testing
Registration Number
NCT02780908
Lead Sponsor
Jozef Stefan Institute
Brief Summary

This project will consist of two studies, each investigating resting and exercise cardio-respiratory responses during exposure to hypoxia in individuals born prematurely and individuals born at full term of two different age groups: Kids (10-14 yrs) and Adults (18-22 yrs).Additional study will be performed on a preterm adult cohort (15 participants) that will investigate potential differences between hypobaric and normobaric hypoxia as outlined in the following section.

Detailed Description

The study protocol in each age group will comprise two visits to the laboratory testing sessions in a randomized order. On one occasion the participants will perform a resting hypoxia test and a graded exercise test to voluntary exhaustion in normoxic condition ((NORM; fraction of inspired oxygen (FiO2)=0.209, placebo). On a second visit the participants will perform a hypoxia sensitivity test and a graded exercise test to voluntary exhaustion in hypoxic condition (HYPO; FiO2=0.120 corresponding to terrestrial altitude of approx. 4000 m). Indirect calorimetry, near infrared spectroscopy and ECG measurements will be performed throughout all tests. During both testing sessions the participants will also undergo anthropometry measurements and pulmonary function testing. The outline of the research visits is presented in the bellow figure:

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
37
Inclusion Criteria

Healthy male individuals

PRETERM group; gestational age: ≤ 32 weeks; gestational weight ≤ 1500 g

CONTROL group: full term born individuals ≤ 38 weeks

Exclusion Criteria

Medication required that may interfere with the interpretation of the results

Chronically illnesses

Hormonal therapy

Recent sub-standard nutritional status

Family history of respiratiory, cardio-vascular, renal or hematological disease History of: thyroid dysfunction, renal stones, diabetes, allergies, hypertension, hypocalcaemia, uric acidaemia, lipidaemia or hyperhomocystinaemia

History of mental illness

Smoker within six months prior to the start of the study

Abuse of drugs, medicine or alcohol

Participation in another study up to two months before study onset

No signed consent form before the onset of the experiment

Blood donors in the past three months before the onset of the experiment

Vegetarian and Vegans

Migraines

History of vestibular disorders

Claustrophobia

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Hypoxia at rest and exerciseGraded exercise testingThe participants will perform a resting test, hypoxia sensitivity test and a graded exercise test to voluntary exhaustion in normoxic condition ((HYPO; FiO2=0.120 corresponding to terrestrial altitude of approx. 4000 m)
Hypoxia at rest and exerciseResting testingThe participants will perform a resting test, hypoxia sensitivity test and a graded exercise test to voluntary exhaustion in normoxic condition ((HYPO; FiO2=0.120 corresponding to terrestrial altitude of approx. 4000 m)
Normoxia at rest and exerciseResting testingThe participants will perform a resting test and a graded exercise test to voluntary exhaustion in normoxic condition ((NORM; fraction of inspired oxygen (FiO2)=0.209, placebo)
Normoxia at rest and exerciseGraded exercise testingThe participants will perform a resting test and a graded exercise test to voluntary exhaustion in normoxic condition ((NORM; fraction of inspired oxygen (FiO2)=0.209, placebo)
Primary Outcome Measures
NameTimeMethod
Cardio-respiratory control at rest in normoxia and hypoxia in preterm and full term individualsOne year

The resting test will be performed in supine position with participants breathing normoxic air (FiO2=0.21) for 30 min and hypoxic gas for the subsequent 30-min (FiO2=0.120). During the whole protocol duration the respiration, local blood flow, ECG and EEG will be measured non-invasively. The resting test will be performed in supine position with participants breathing normoxic air (FiO2=0.21) for 30 min and hypoxic gas for the subsequent 30-min (FiO2=0.120). During the whole protocol duration the respiration, local blood flow, ECG and EEG will be measured non-invasively.

Tolerance to hypoxia during rest and exercise in preterm and full term individualsTwo year

All graded exercise tests will be performed on electromagnetically controlled cycle-ergometer Ergo Bike Premium.The participants will be required to maintain a cadence of 60·min-1 throughout the whole test. The test is terminated when the participant is unable to maintain the assigned cadence. The resting test will be performed in supine position with participants breathing normoxic air (FiO2=0.21) for 30 min and hypoxic gas for the subsequent 30-min (FiO2=0.120). During the whole protocol duration the respiration, local blood flow, ECG and EEG will be measured non-invasively. The resting test will be performed in supine position with participants breathing normoxic air (FiO2=0.21) for 30 min and hypoxic gas for the subsequent 30-min (FiO2=0.120). During the whole protocol duration the respiration, local blood flow, ECG and EEG will be measured non-invasively.

Secondary Outcome Measures
NameTimeMethod
Sensitivity to hypoxia during rest and exercise - Richalet testOne year

This test will assess individuals tolerance to hypoxia and HVR. As noted in the above figure the test consist of a 4-min periods of normoxic (FiO2=0.210) and hypoxic (FiO2=0.120) rest and hypoxic and normoxic low-intensity exercise. Respiration, gas exchange and capillary oxygen saturation will be measured during the course of the test.

Changes in intestinal metabolites as a result of hypoxic exposureOne year

The aim of this protocol is to assess whether there are significant differences in physiological status of intestinal metabolites (reducing sugars, short chain fatty acids, amino-acids, index of molecular weight, polyphenols, sterols) between the two populations in response to normoxic and hypoxic testing procedures. As sampling needs to be conducted during the period preceding the actual days of experiments and after the completion of testing, i.e. during the daily routines of participants, auto-sampling protocol was selected as the only option through which samples of feces and urine are going to be collected by participants three days before and after physical testing.

Differences between normobaric and hypobaric hypoxia in preterm individualsTwo years

This part of the study will investigate potential differences between normobaric and hypobaric exposure to hypoxia in preterm born individuals. For this purpose the participants will perform another laboratory visit in Ljubljana and will also be exposed to hypobaric hypoxia in a physiology lab at Aiguille du Midi, which is run by our collaborators. As noted in the bellow schematic each exposure will last 8-hours and measures of respiration, gas exchange and blood sampling will be performed at 2-4 hour periods during the exposure. The participants will be transferred to Chamonix using a van with our research team in groups of four. The transfer from Chamonix to Aiguille du Midi laboratory will be performed via cable car

Oxidative stress responses to hypoxic exercise in preterm and full termOne year

Blood sampling will be performed during each visit at four time points (before and after each test, as detailed on the bellow figure. Besides general hematological markers (CBC, ferritin, transferrin etc.) oxidative stress (advanced oxidation protein products, malondialdehyde and nitrotyrosine) and antioxidant system markers (superoxide dismutase, catalase, ferric-reducing antioxidant power, glutathione peroxidase and uric acid) will be determined as described previously (3). Select gene polymorphisms and their association with the above mentioned oxidative stress markers will also be assessed from the collected blood samples in collaboration with the laboratory for Pharmacogenetics, Medical Faculty, UL

Trial Locations

Locations (2)

Jozef Stefan Institute

🇸🇮

Ljubljana, Slovenia

University Children's Hospital Ljubljana Department of Pediatric Neurology

🇸🇮

Ljubljana, Slovenia

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