Hypoxia Intolerance in Preterm Individuals

NCT04739904 | Completed

• 1 other identifier: PreAlti
• Study Type: observational
• Target: 36
• Locations: 2 countries
• Sites: 3

Brief Summary

Reduced Hypoxic Ventilatory Response (HVR) and systemic O2 saturation subsequently leading to blunted aerobic capacity as well as decreased overall physical and cognitive performance are the main physiological challenges faced by prematurely born individuals in hypobaric hypoxia (i.e. during high altitude sojourn). While these phenomena have been described previously, the underlying mechanisms are currently unresolved. Given that the reduction in altitude-performance and its underlying mechanisms are not well understood, it is currently impossible to give evidence-based recommendation for altitude sojourns in this cohort. It is also of note, that even hypobaric hypoxia exposure during long-haul flights might be detrimental to well-being of pre-term born individuals. The present project aims to comprehensively investigate physiological responses to altitude/hypoxia during rest and exercise in prematurely born, but otherwise healthy adults. Specifically, the investigators aim to elucidate the underlying mechanisms of the altered resting and exercise cardiovascular, respiratory, cerebral and hematological responses to hypoxia in prematurely born individuals. The obtained results from this cohort will be compared to the data from a control groups consisting of healthy, age and aerobic capacity-matched individuals born at full-term. While acute hypoxic effects will be the focus of the project's first phase, the researchers will test the effect of prolonged terrestrial (real) or simulated (normobaric hypoxia) altitude exposures in the second part. This phase will, in addition to the insight into the prolonged altitude acclimatization modulation in prematurely born individuals, also enable the potential differences between the effects of normobaric (simulated) and hypobaric (terrestrial) hypoxia in this cohort to be investigated.

Conditions

Premature Birth; Hypoxia

Keywords

Acclimatization; Altitude; Preterm birth; Cardiorespiratory; Cerebrovascular; Exercise

Outcome Measures

Primary Outcomes (17)

• Cerebrovascular reactivity to carbon dioxide (CO2)

  Subjects will breath 4 min 3% CO2 and 4 min 6% CO2 separated by 4 min of breathing ambient air. Gas exchange, blood flow in the middle cerebral artery and peripheral oxygen saturation will be continuously recorded by metabolic cart, transcranial doppler, and finger pulse oximeter, respectively.

  48 hours after exposure to normoxia and hypobaric hypoxia, respectively.

• Cognitive function

  Cognitive function will be assessed by a computerized psychometric test battery previously used by our research group. These will assess working memory and visuo-motor coordination.

  24 hours after exposure to normoxia, hypobaric hypoxia, and normobaric hypoxia, respectively

• Acute Mountain Sickness (AMS)

  AMS will be assessed by Lake Louise scale. AMS will be diagnosed if the Lake Louise score is 3 or higher.

  8 hours (prior to sleep) and 16 hours (upon waking) after exposure to hypobaric and normobaric hypoxia

• Change in respiratory function

  Respiratory function will be assessed by spirometry.

  Immediately after exposure to hypobaric and normobaric hypoxia, relative to baseline.

• Lung comets

  Lung comets will be assessed by counting the number of B-lines present, which will be measured using Doppler ultrasound.

  Every day before and immediately after each exercise bout.

• Heart rate response to exercise

  Heart rate (HR, bpm) will be continuously monitored during different exercise bouts of variety intensities (moderate and heavy intensities will be used).

  Every day before exercise, during exercise and at the instant of volitional exhaustion.

• Respiratory response to exercise

  Oxygen consumption (VO2, L/min and mL/min/kg) will be continuously monitored during different exercise bouts of variety intensities (moderate and heavy intensities will be used).

  Every day before exercise, during exercise and at the instant of volitional exhaustion.

• Changes in muscular oxygenation during exercise

  Muscle oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed on the vastus lateralis. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin and myoglobin (microM) in the investigated areas (vastus lateralis).

  Every day before exercise, during exercise and at the instant of volitional exhaustion.

• Changes in cerebral oxygenation during exercise

  Brain oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed at the frontal levels. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin (microM) in the investigated areas (prefrontal cortex).

  Every day before exercise, during exercise and at the instant of volitional exhaustion.

• Changes in the rate of muscular oxygen consumption (mV̇O2)

  Muscle oxygen consumption will be assessed using a previously validated protocol. Briefly, a Near Infra-Red Spectroscopy (NIRS) optode will be placed on the vastus lateralis muscle. Before the protocol, an ischemic calibration will be performed to normalize the NIRS signals by inflating the blood pressure cuff to 250-300 mmHg for a maximum of 5 min. Resting mV̇O2 will be assessed from the decrease in muscle oxygenation which accompanies the arterial occlusion. Four resting measurements will be performed using 10 sec of arterial occlusion. Then, each subject will perform a voluntary knee extension exercise for 15 sec. To measure the recovery of oxygen consumption after exercise, subject will have a series of arterial occlusion as follows: 5 occlusions 5sec on-5sec off, 5 occlusions 5sec on-5sec off, and 8 occlusions 10 sec on-20 sec off.

  Before each exercise bouts.

• Acute change in sleep quality

  Polysomnography will be used to assess sleep quality. Measurements will include electroencephalography (EEG), electrooculography (EOG), chin and tibial surface electromyography (EMG), electrocardiography (ECG), nasal pressure (nasal pressure cannula), respiratory movements (chest and abdominal belts) as well as capillary oxygenated haemoglobin saturation measurement.

  On the first night in normoxia, normobaric hypoxia and hypobaric hypoxia.

• Change in sleep quality after prolonged exposure to hypobaric hypoxia

  Polysomnography will be used to assess sleep quality. Measurements will include electroencephalography (EEG), electrooculography (EOG), chin and tibial surface electromyography (EMG), electrocardiography (ECG), nasal pressure (nasal pressure cannula), respiratory movements (chest and abdominal belts) as well as capillary oxygenated haemoglobin saturation measurement.

  On the third night after exposure to terrestrial altitude.

• Changes in endothelial capacity to flow-mediated dilation (FMD)

  A pneumatic cuff is positioned distal to the ultrasound probe in order to avoid ischemia of the artery studied. Radial artery diameter is measured at rest, during inflation of the distal cuff to suprasystolic pressure (5 min) and for the 5 min following deflation. The subsequent decrease in local blood flow in response to ischemia causes a progressive decrease in the radial artery diameter until a plateau (L-FMC). Upon cuff deflation, the increased blood flow causes radial artery dilatation. L-FMC is calculated as the percentage decrease in arterial diameter in the last 30 s of cuff occlusion as compared with resting diameter. FMD is calculated as the maximum percentage increase in arterial diameter following cuff deflation.

  24 hours after exposure to normoxia and hypobaric hypoxia.

• Changes in orthostatic tolerance

  Orthostatic tolerance will be assessed by measuring heart rate variability. This will involve an app-validated 10-min protocol, which will use a chest-band to monitor heart rate changes from 5 minutes of supine position followed by 5 minutes of standing.

  At 6am on every trial day (upon waking).

• Changes in oxidative stress markers in the blood

  Oxidative stress markers concentration will be measured on collected venous blood sample.

  Blood samples will be collected at 6am (upon waking).

• Change in salivary cortisol concentration

  Cortisol concentration will be measured on collected saliva samples.

  Saliva samples will be collected at 6am (upon waking).

• Change in hydration status

  Urine samples will be assessed using urine specific gravity.

  Urine samples will be collected at 6am (upon waking).

Secondary Outcomes (1)

• Change in cerebral blood flow in the internal carotid artery

  Cerebral blood flow will be measured at 10am.

Study Arms (2)

Preterm born

Premature born but otherwise healthy adults exposed to normoxic, normobaric hypoxic and hypobaric hypoxic interventions.

Other: Normoxia; Other: Normobaric hypoxia; Other: Hypobaric hypoxia

Full-term control

Full-term born healthy adults exposed to normoxic, normobaric hypoxic and hypobaric hypoxic interventions.

Other: Normoxia; Other: Normobaric hypoxia; Other: Hypobaric hypoxia

Interventions

Normoxia OTHER

48 hours experimental protocol conducted at sea level

Also known as: Normoxic condition, Sea level

Full-term control; Preterm born

Normobaric hypoxia OTHER

24 hours experimental protocol conducted in a normobaric hypoxic facility

Also known as: Simulated altitude

Full-term control; Preterm born

Hypobaric hypoxia OTHER

72 hours experimental protocol conducted at terrestrial altitude

Also known as: Terrestrial altitude

Full-term control; Preterm born

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Prematurely born adults involved in this study must fulfil the following characteristics at birth: gestational age ≤ 32 weeks and gestational weight ≤ 1500g. Conversely, full-term adults involved in this study must fulfil the following characteristics at birth: gestational age of at least 38 weeks.

You may qualify if:

• prematurely born (gestational age: ≤ 32 weeks; gestational weight ≤ 1500g)
• full-term born
• healthy individuals
• male

You may not qualify if:

• presence of any medical risk factors to exercise and/or exposure to altitude
• presence of any medical condition that would make the protocol unreasonably hazardous for the patient
• smokers
• exposure to altitude above 1000m in the last 2 months

Sponsors & Collaborators

• Jozef Stefan Institute: lead
• University of Lausanne: collaborator

Study Sites (3)

Jozef Stefan Institute

Ljubljana, 1000, Slovenia

Location

University of Ljubljana

Ljubljana, 1000, Slovenia

Location

Institute of Sport Sciences of the University of Lausanne

Lausanne, Canton of Vaud, 1015, Switzerland

Location

Related Publications (1)

• Manferdelli G, Narang BJ, Bourdillon N, Debevec T, Millet GP. Physiological Responses to Exercise in Hypoxia in Preterm Adults: Convective and Diffusive Limitations in the O 2 Transport. Med Sci Sports Exerc. 2023 Mar 1;55(3):482-496. doi: 10.1249/MSS.0000000000003077. Epub 2022 Oct 26.

  PMID: 36459101 DERIVED

MeSH Terms

Conditions

Premature Birth; Hypoxia; Motor Activity

Interventions

Sea Level Rise

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Oceans and Seas; Geological Phenomena; Physical Phenomena; Climate Change; Climatic Processes; Ecological and Environmental Phenomena; Biological Phenomena; Water Movements

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: February 5, 2021
• Study Start: April 30, 2021
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

CH (1); SL (2)