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Mechanisms Underlying Hypoxic, Heat and Cross-tolerance Adaptation in Women

Not Applicable
Not yet recruiting
Conditions
Heat Exposure
Exercise Training
Registration Number
NCT06575985
Lead Sponsor
Jozef Stefan Institute
Brief Summary

This study will consist of a parallel-groups design, with 30 healthy active female participants randomly assigned to either an experimental heat acclimation and exercise intervention, or a thermo-neutral exercise intervention control group. Interventions will be 10 days in duration, and consist of daily 60-minute exercise bouts under the appropriate environmental condition. Before and after each intervention, various tests will be conducted to establish exercise capacity under various environmental conditions, as well as underlying mechanisms of physiological adaptation induced by each intervention.

Detailed Description

Most research on how the human body responds to different environmental conditions has primarily focused on men, leaving a gap in our understanding of how women adapt to these conditions. Heat exposure in particular is known to affect the well-being and performance of humans, as well as induce chronic adaptations through an acclimation/acclimatization process, which helps the body to better regulate core temperature. Moreover, contemporary research is beginning to explore the 'cross-tolerance' phenomenon; the notion that exposure (and acclimation/acclimatization) to one environmental stressor may affect the responses to another. In particular, both heat and hypoxia are known to activate common acclimatization pathways, with pulmonary, cardiovascular, hematological and muscular adaptations occurring to facilitate both oxygen transport and core body temperature regulation. In line with this background, the primary aim of this study is to investigate the effects of a heat acclimation and exercise intervention, relative to a thermo-neutral exercise control intervention, on exercise tolerance under various environmental conditions (heat, hypoxia, neutral) in healthy, active women. The secondary aim is to establish mechanisms of adaptation, by exploring the intervention-induced changes in pulmonary, cardiovascular, hematological and muscular factors, through various tests conducted at rest and during exercise.

To address these aims, 30 healthy active female participants, aged between 18 and 35 years, will be randomized to either an experimental (heat acclimation and exercise training) or control (thermo-neutral exercise training) group. The experimental group will complete a 10-day heat acclimation training intervention, exercising for 60 minutes per day in a climactic chamber set to 35°C and 50% relative humidity. The control group will complete a similar exercise intervention, but under thermo-neutral conditions (23°C and 50% relative humidity). Before and after the intervention period, both groups will complete a wide variety of tests, including exercise capacity measurements under each environmental condition (heat \[35°C\], hypoxia \[Fraction of inspired oxygen = 0.135\], neutral \[23°C, FiO2 = 0.209\]), body composition assessments, lung function testing, hemoglobin mass and blood volume quantification, skeletal muscle mitochondrial function and vascular responsiveness assessment, and venous blood sampling for a variety of sex hormone-, redox balance-, hematopoietic-, heat shock protein-, hypoxia-inducible factor- and genetic-related markers.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
30
Inclusion Criteria
  • Age: 18 - 35 years
  • Body mass index: 18.5 - 25.0 kg/m^2
  • Regular physical activity (at least 30 minutes of moderate-intensity activity, three times per week)
Exclusion Criteria
  • Habitual smoker within the past 5 years
  • History of metabolic disorders or any medications deemed to pose an undue risk or introduce bias in any outcome measures
  • Exposure to altitude > 2000 m above sea level within four weeks of scheduled participation
  • Permanent residence at altitude > 1000 m above sea level

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Exercise capacity under thermo-neutral hypoxic conditionsMeasured once before (pre) and once up to 1 week after (post) the intervention period

Results of an incremental exercise test to exhaustion conducted at 23°C and an FiO2 of 0.135, quantified using maximal oxygen uptake

Exercise capacity under thermo-neutral normoxic conditionsMeasured once before (pre) and once up to 1 week after (post) the intervention period

Results of an incremental exercise test to exhaustion conducted at 23°C and an FiO2 of 0.209, quantified using maximal oxygen uptake

Exercise capacity under hot normoxic conditionsMeasured once before (pre) and once up to 1 week after (post) the intervention period

Results of an incremental exercise test to exhaustion conducted at 35°C and an FiO2 of 0.209, quantified using maximal oxygen uptake

Secondary Outcome Measures
NameTimeMethod
Muscle oxygenation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Vastus lateralis oxygenation measured throughout the incremental exercise tests using near-infrared spectroscopy.

Pulse oxygen saturation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Capillary oxygen saturation measured on the right earlobe throughout the incremental exercise tests using pulse oximetry.

Core body temperature regulation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Core body temperature measured throughout the incremental exercise tests using a rectal temperature probe.

Brain oxygenation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Cerebral oxygenation measured at the left pre-frontal cortex throughout the incremental exercise tests using near-infrared spectroscopy.

Hemoglobin massMeasured once before (pre) and once up to 1 week after (post) the intervention period

Hemoglobin mass estimation using the carbon monoxide re-breathing method

Skin temperature regulation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Skin temperature measured throughout the incremental exercise tests using temperature probes attached to the calf, thigh, chest and arm, from which weighted averages are calculated.

Sweat rates during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Sweat rate measured throughout the incremental exercise tests using a sensor attached to the forehead.

Hemo-dynamic activity during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Cardiac output measured throughout the incremental exercise tests by bio-electrical impedance cardiography.

Pulmonary ventilation during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Pulmonary ventilation measured throughout the incremental exercise tests using flow measurements as recorded by metabolic cart.

Gas exchange during exerciseMeasured once before (pre) and once up to 1 week after (post) the intervention period

Balance of oxygen uptake and carbon dioxide production measured throughout the incremental exercise tests using gas composition sensors recorded by metabolic cart.

Body compositionMeasured once before (pre) and once up to 1 week after (post) the intervention period

Body mass measured using standard weighing scales, with body fat percentage estimated using a standardized eight-site skinfold measurement protocol with associated equation.

Blood/plasma volumeMeasured once before (pre) and once up to 1 week after (post) the intervention period

Blood/plasma volume estimation using the carbon monoxide re-breathing method

Skeletal muscle mitochondrial functionMeasured once before (pre) and once up to 1 week after (post) the intervention period

Skeletal muscle mitochondrial function quantified using a peripheral vascular occlusion test, with the rate of decrease in muscle oxygenation used to estimate mitochondrial function.

Lung functionMeasured once before (pre) and once up to 1 week after (post) the intervention period

Standard spirometry procedure to assess lung function using forced expiratory volume

Hypoxia-inducible factor 1αMeasured once before (pre) and once up to 1 week after (post) the intervention period

Venous blood samples will be obtained to measure hypoxia-inducible factor 1α in the extracted plasma and serum.

Skeletal muscle vascular responsivenessMeasured once before (pre) and once up to 1 week after (post) the intervention period

Skeletal muscle vascular responsiveness quantified using a peripheral vascular occlusion test, with the rate of increase in muscle oxygenation during re-perfusion, and the oxygenation overshoot relative to pre-occlusion baseline, used to estimate vascular responsiveness.

Oxidative stress markerMeasured once before (pre) and once up to 1 week after (post) the intervention period

Venous blood samples will be obtained to quantify redox balance from the extracted plasma.

HematopoiesisMeasured once before (pre) and once up to 1 week after (post) the intervention period

Venous blood samples will be obtained to measure various markers of hematopoiesis from the extracted plasma, serum and/or whole blood.

Blood viscosityMeasured once before (pre) and once up to 1 week after (post) the intervention period

Blood viscosity will be measured by obtaining venous blood samples from the participants, extracting plasma, and using a cone/plate viscometer to quantify viscosity and varying shear rates.

Heat shock proteinsMeasured once before (pre) and once up to 1 week after (post) the intervention period

Venous blood samples will be obtained to measure heat shock proteins in the extracted plasma and serum.

Trial Locations

Locations (2)

Jozef Stefan Institute

🇸🇮

Ljubljana, SI, Slovenia

University of Ljubljana

🇸🇮

Ljubljana, Slovenia

Jozef Stefan Institute
🇸🇮Ljubljana, SI, Slovenia
Benjamin Narang, MSci
Contact
+38640569967
benjamin.narang@ijs.si

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