Clinical trial NCT06575985: Mechanisms Underlying Hypoxic, Heat and Cross-tolerance Adaptation in Women
Official title: Investigating the Effects of a 10-day Heat Acclimation and Exercise Intervention on Physiological Adaptations and Cross-tolerance in Women
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Heat Exposure
Exercise Training
Lead sponsor: Jozef Stefan Institute
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
name: University of Ljubljana, Faculty of Medicine
First posted: 2024-08-28
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Exercise capacity under thermo-neutral normoxic conditions
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Exercise capacity under hot normoxic conditions
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Exercise capacity under thermo-neutral hypoxic conditions
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
Secondary outcomes:
measure: Core body temperature regulation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Skin temperature regulation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Sweat rates during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Hemo-dynamic activity during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Pulmonary ventilation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Gas exchange during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Muscle oxygenation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Brain oxygenation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Pulse oxygen saturation during exercise
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Body composition
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Lung function
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Hemoglobin mass
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Blood/plasma volume
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Skeletal muscle mitochondrial function
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Skeletal muscle vascular responsiveness
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Blood viscosity
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Oxidative stress marker
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Hematopoiesis
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Heat shock proteins
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Hypoxia-inducible factor 1α
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
Other outcomes:
measure: Oestrogen
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Progesterone
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
measure: Single nucleotide polymorphisms
timeFrame: Measured once before (pre) and once up to 1 week after (post) the intervention period
Locations:
city: Ljubljana
country: Slovenia
facility: Jozef Stefan Institute
state: SI
city: Ljubljana
country: Slovenia
facility: University of Ljubljana
Study officials:
affiliation: University of Ljubljana
name: Tadej Debevec, PhD
role: PRINCIPAL_INVESTIGATOR
References: