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Cardio-respiratory Responses During Hypoxic Exercise in Individuals Born Prematurely (PreTerm)

Primary Purpose

Hypoxia, Altitude Sickness, Tolerance

Status
Unknown status
Phase
Not Applicable
Locations
Slovenia
Study Type
Interventional
Intervention
Graded exercise testing
Resting testing
Sponsored by
Jozef Stefan Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hypoxia

Eligibility Criteria

18 Years - 24 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Jozef Stefan InstituteRecruiting
  • University Children's Hospital Ljubljana Department of Pediatric NeurologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Hypoxia at rest and exercise

Normoxia at rest and exercise

Arm Description

The 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)

The 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)

Outcomes

Primary Outcome Measures

Tolerance to hypoxia during rest and exercise in preterm and full term individuals
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.
Cardio-respiratory control at rest in normoxia and hypoxia in preterm and full term individuals
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

Oxidative stress responses to hypoxic exercise in preterm and full term
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
Sensitivity to hypoxia during rest and exercise - Richalet test
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 exposure
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 individuals
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

Full Information

First Posted
May 19, 2016
Last Updated
August 29, 2016
Sponsor
Jozef Stefan Institute
Collaborators
University of Ljubljana School of Medicine, Slovenia, University Medical Centre Ljubljana, University of Lausanne, University of Lyon, Lancaster University, University of Ljubljana
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1. Study Identification

Unique Protocol Identification Number
NCT02780908
Brief Title
Cardio-respiratory Responses During Hypoxic Exercise in Individuals Born Prematurely
Acronym
PreTerm
Official Title
Cardio-respiratory Responses During Hypoxic Exercise in Individuals Born Prematurely
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2016 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jozef Stefan Institute
Collaborators
University of Ljubljana School of Medicine, Slovenia, University Medical Centre Ljubljana, University of Lausanne, University of Lyon, Lancaster University, University of Ljubljana

4. Oversight

Data Monitoring Committee
No

5. Study Description

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:

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxia, Altitude Sickness, Tolerance

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
37 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hypoxia at rest and exercise
Arm Type
Experimental
Arm Description
The 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)
Arm Title
Normoxia at rest and exercise
Arm Type
Placebo Comparator
Arm Description
The 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)
Intervention Type
Other
Intervention Name(s)
Graded exercise testing
Intervention Description
All graded exercise tests will be performed on electromagnetically controlled cycle-ergometer Ergo Bike Premium. The testing protocol will commence with a 10-min resting period, to obtain the resting cardio-respiratory values, followed by a 5-min warm up at a work rate of 60 W. Thereafter the workload will increase every fourth minute by 40 W. 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.
Intervention Type
Other
Intervention Name(s)
Resting testing
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tolerance to hypoxia during rest and exercise in preterm and full term individuals
Description
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.
Time Frame
Two year
Title
Cardio-respiratory control at rest in normoxia and hypoxia in preterm and full term individuals
Description
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.
Time Frame
One year
Secondary Outcome Measure Information:
Title
Oxidative stress responses to hypoxic exercise in preterm and full term
Description
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
Time Frame
One year
Title
Sensitivity to hypoxia during rest and exercise - Richalet test
Description
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.
Time Frame
One year
Title
Changes in intestinal metabolites as a result of hypoxic exposure
Description
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.
Time Frame
One year
Title
Differences between normobaric and hypobaric hypoxia in preterm individuals
Description
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
Time Frame
Two years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
24 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Damjan Osredkar, MD, PhD
Phone
+38615229273
Email
damjan.osredkar@kclj.si
First Name & Middle Initial & Last Name or Official Title & Degree
Tadej Debevec, PhD
Phone
+38641278954
Email
tadej.debevec@ijs.si
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damjan Osredkar, MD, PhD
Organizational Affiliation
University Children's Hospital Ljubljana Department of Pediatric Neurology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jozef Stefan Institute
City
Ljubljana
ZIP/Postal Code
1000
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tadej Debevec, PhD
Phone
+38641278954
Email
tadej.debevec@ijs.si
First Name & Middle Initial & Last Name & Degree
Igor B. Mekjavic, PhD
Phone
+386 1 477 3358
Email
igor.mekjavic@ijs.si
Facility Name
University Children's Hospital Ljubljana Department of Pediatric Neurology
City
Ljubljana
ZIP/Postal Code
1000
Country
Slovenia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Damjan Osredkar, MD PhD
Phone
+386.1.522.9273
Email
damjan.osredkar@kclj.si
First Name & Middle Initial & Last Name & Degree
Minca Mramor, MD PhD
Phone
+386.1.522.9286
Email
minca.mramor@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23846158
Citation
Debevec T, Pialoux V, Mekjavic IB, Eiken O, Mury P, Millet GP. Moderate exercise blunts oxidative stress induced by normobaric hypoxic confinement. Med Sci Sports Exerc. 2014 Jan;46(1):33-41. doi: 10.1249/MSS.0b013e31829f87ef.
Results Reference
background
PubMed Identifier
22406250
Citation
Debevec T, Mekjavic IB. Short intermittent hypoxic exposures augment ventilation but do not alter regional cerebral and muscle oxygenation during hypoxic exercise. Respir Physiol Neurobiol. 2012 Apr 30;181(2):132-42. doi: 10.1016/j.resp.2012.02.008. Epub 2012 Mar 2.
Results Reference
background
PubMed Identifier
21735214
Citation
Debevec T, Keramidas ME, Norman B, Gustafsson T, Eiken O, Mekjavic IB. Acute short-term hyperoxia followed by mild hypoxia does not increase EPO production: resolving the "normobaric oxygen paradox". Eur J Appl Physiol. 2012 Mar;112(3):1059-65. doi: 10.1007/s00421-011-2060-7. Epub 2011 Jul 7.
Results Reference
background
PubMed Identifier
20377142
Citation
Debevec T, Amon M, Keramidas ME, Kounalakis SN, Pisot R, Mekjavic IB. Normoxic and hypoxic performance following 4 weeks of normobaric hypoxic training. Aviat Space Environ Med. 2010 Apr;81(4):387-93. doi: 10.3357/asem.2660.2010.
Results Reference
background
PubMed Identifier
26796757
Citation
Debevec T, Pialoux V, Ehrstrom S, Ribon A, Eiken O, Mekjavic IB, Millet GP. FemHab: The effects of bed rest and hypoxia on oxidative stress in healthy women. J Appl Physiol (1985). 2016 Apr 15;120(8):930-8. doi: 10.1152/japplphysiol.00919.2015. Epub 2016 Jan 21.
Results Reference
background
PubMed Identifier
24887106
Citation
Debevec T, Simpson EJ, Macdonald IA, Eiken O, Mekjavic IB. Exercise training during normobaric hypoxic confinement does not alter hormonal appetite regulation. PLoS One. 2014 Jun 2;9(6):e98874. doi: 10.1371/journal.pone.0098874. eCollection 2014.
Results Reference
background
PubMed Identifier
26087775
Citation
Osredkar D, Sabir H, Falck M, Wood T, Maes E, Flatebo T, Puchades M, Thoresen M. Hypothermia Does Not Reverse Cellular Responses Caused by Lipopolysaccharide in Neonatal Hypoxic-Ischaemic Brain Injury. Dev Neurosci. 2015;37(4-5):390-7. doi: 10.1159/000430860. Epub 2015 Jun 12.
Results Reference
background
PubMed Identifier
24361672
Citation
Osredkar D, Thoresen M, Maes E, Flatebo T, Elstad M, Sabir H. Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic-ischemic brain injury. Resuscitation. 2014 Apr;85(4):567-72. doi: 10.1016/j.resuscitation.2013.12.006. Epub 2013 Dec 19.
Results Reference
background
PubMed Identifier
32270264
Citation
Debevec T, Pialoux V, Poussel M, Willis SJ, Martin A, Osredkar D, Millet GP. Cardio-respiratory, oxidative stress and acute mountain sickness responses to normobaric and hypobaric hypoxia in prematurely born adults. Eur J Appl Physiol. 2020 Jun;120(6):1341-1355. doi: 10.1007/s00421-020-04366-w. Epub 2020 Apr 8.
Results Reference
derived

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Cardio-respiratory Responses During Hypoxic Exercise in Individuals Born Prematurely

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