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

Investigating the Effects of a 10-day Heat Acclimation and Exercise Intervention on Physiological Adaptations and Cross-tolerance in Women

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Exercise Training; Heat Exposure
• Intervention / Treatment: Other: Heat acclimation and exercise training; Other: Thermo-neutral exercise training group

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tadej Debevec, PhD; Phone Number: +38615207726; Email: tadej.debevec@fsp.uni-lj.si
• Study Contact Backup: Name: Benjamin J Narang, MSci; Phone Number: +38640569967; Email: benjamin.narang@ijs.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University of Ljubljana
  • SI
    • Ljubljana, SI, Slovenia, 1000
      • Jozef Stefan Institute
      • Contact: Benjamin Narang, MSci; Phone Number: +38640569967; Email: benjamin.narang@ijs.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Heat acclimation and exercise group; Experimental group who will complete an exercise training intervention under hot conditions	Other: Heat acclimation and exercise training; 10-day intervention consisting of daily 60-min exercise sessions aimed to induce increases in core body temperature, conducted in a climactic chamber set to 35°C and 50% relative humidity.
Active Comparator: Thermo-neutral exercise training group; Control group who will complete an exercise training intervention under thermo-neutral conditions	Other: Thermo-neutral exercise training group; 10-day intervention consisting of daily 60-min exercise sessions conducted in a climactic chamber set to 23°C and 50% relative humidity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise capacity under thermo-neutral normoxic conditions	Results of an incremental exercise test to exhaustion conducted at 23°C and an FiO2 of 0.209, quantified using maximal oxygen uptake	Measured once before (pre) and once up to 1 week after (post) the intervention period
Exercise capacity under hot normoxic conditions	Results of an incremental exercise test to exhaustion conducted at 35°C and an FiO2 of 0.209, quantified using maximal oxygen uptake	Measured once before (pre) and once up to 1 week after (post) the intervention period
Exercise capacity under thermo-neutral hypoxic conditions	Results of an incremental exercise test to exhaustion conducted at 23°C and an FiO2 of 0.135, quantified using maximal oxygen uptake	Measured once before (pre) and once up to 1 week after (post) the intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Core body temperature regulation during exercise	Core body temperature measured throughout the incremental exercise tests using a rectal temperature probe.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Skin temperature regulation during exercise	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.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Sweat rates during exercise	Sweat rate measured throughout the incremental exercise tests using a sensor attached to the forehead.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Hemo-dynamic activity during exercise	Cardiac output measured throughout the incremental exercise tests by bio-electrical impedance cardiography.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Pulmonary ventilation during exercise	Pulmonary ventilation measured throughout the incremental exercise tests using flow measurements as recorded by metabolic cart.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Gas exchange during exercise	Balance of oxygen uptake and carbon dioxide production measured throughout the incremental exercise tests using gas composition sensors recorded by metabolic cart.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Muscle oxygenation during exercise	Vastus lateralis oxygenation measured throughout the incremental exercise tests using near-infrared spectroscopy.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Brain oxygenation during exercise	Cerebral oxygenation measured at the left pre-frontal cortex throughout the incremental exercise tests using near-infrared spectroscopy.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Pulse oxygen saturation during exercise	Capillary oxygen saturation measured on the right earlobe throughout the incremental exercise tests using pulse oximetry.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Body composition	Body mass measured using standard weighing scales, with body fat percentage estimated using a standardized eight-site skinfold measurement protocol with associated equation.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Lung function	Standard spirometry procedure to assess lung function using forced expiratory volume	Measured once before (pre) and once up to 1 week after (post) the intervention period
Hemoglobin mass	Hemoglobin mass estimation using the carbon monoxide re-breathing method	Measured once before (pre) and once up to 1 week after (post) the intervention period
Blood/plasma volume	Blood/plasma volume estimation using the carbon monoxide re-breathing method	Measured once before (pre) and once up to 1 week after (post) the intervention period
Skeletal muscle mitochondrial function	Skeletal muscle mitochondrial function quantified using a peripheral vascular occlusion test, with the rate of decrease in muscle oxygenation used to estimate mitochondrial function.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Skeletal muscle vascular responsiveness	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.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Blood viscosity	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.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Oxidative stress marker	Venous blood samples will be obtained to quantify redox balance from the extracted plasma.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Hematopoiesis	Venous blood samples will be obtained to measure various markers of hematopoiesis from the extracted plasma, serum and/or whole blood.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Heat shock proteins	Venous blood samples will be obtained to measure heat shock proteins in the extracted plasma and serum.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Hypoxia-inducible factor 1α	Venous blood samples will be obtained to measure hypoxia-inducible factor 1α in the extracted plasma and serum.	Measured once before (pre) and once up to 1 week after (post) the intervention period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oestrogen	Oestrogen will be quantified in the plasma extracted from venous blood samples, to identify the menstrual cycle phases of the participants.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Progesterone	Progesterone will be quantified in the plasma extracted from venous blood samples, to identify the menstrual cycle phases of the participants.	Measured once before (pre) and once up to 1 week after (post) the intervention period
Single nucleotide polymorphisms	Venous blood samples will be processed and analysed to identify single nucleotide polymorphisms	Measured once before (pre) and once up to 1 week after (post) the intervention period

Collaborators and Investigators

• Sponsor: Jozef Stefan Institute
• Collaborators: University of Ljubljana; University of Ljubljana, Faculty of Medicine
• Investigators: Principal Investigator: Tadej Debevec, PhD, University of Ljubljana

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: FemAdapt_HEAT; J5-50180 (Other Grant/Funding Number: Javna Agencija za Raziskovalno Dejavnost RS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the study, after de-identification, will be made publicly available using an online data repository.
• IPD Sharing Time Frame: Data will be made available immediately following publication with no end date.
• IPD Sharing Access Criteria: Any purpose.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No