Comparison of a Novel Condensed Heat Acclimation Programme With a Traditional Longer-term Heat Acclimation Programme

Study Overview
=================
Brief Summary
-----------------
Repeated exposure to heat in a laboratory setting (acclimation) elicits a range of adaptations, which reduce heat illness risk and increase work capacity in the heat. Traditional approaches to heat acclimation require daily heat exposures of 1 to 2 hours over  7 to 10 consecutive days. Heat acclimation approaches which reduce the number of days to achieve acclimation may have utility. The primary purpose of the proposed research is to determine whether it is possible to achieve a similar degree of heat acclimation to that seen with a traditional longer-term heat acclimation approach by increasing the frequency of heat exposure, utilising multiple daily heat exposures over a smaller number of days. Secondary aims of the research are to examine whether heat acclimation provides cross-adaptation to a hypoxic stressor and whether heat acclimation improves aerobic fitness.

Detailed Description
-----------------
Individuals are often required to operate in adverse conditions and may be exposed to prolonged periods of high ambient heat and humidity. High environmental temperatures impair work capacity and increase heat-illness risk. Repeated exposure to heat in a laboratory setting (acclimation) elicits a range of adaptations, which reduce heat illness risk and increase work capacity in the heat. However, traditional approaches to heat acclimation are time consuming, typically requiring daily heat exposures of 1 to 2 hours over  7 to 10 consecutive days. This can be logistically difficult to implement and impractical, particularly in situations where an individual must be rapidly deployed. Therefore, heat acclimation approaches which reduce the number of days to achieve acclimation may have utility. In addition, recent research studies have suggested that adaptation to heat may improve tolerance to hypoxia (cross-adaptation) and improve aerobic fitness; these effects may also be beneficial in a military context. Therefore, the primary purpose of the proposed research is to determine whether it is possible to achieve a similar degree of heat acclimation to that seen with a traditional longer-term heat acclimation approach by increasing the frequency of heat exposure, utilising multiple daily heat exposures over a smaller number of days. Secondary aims of the research are to examine whether heat acclimation provides cross-adaptation to a hypoxic stressor and whether heat acclimation improves aerobic fitness. Heat acclimation will be evaluated using a range of whole-body (cardiovascular, thermoregulatory, psychophysiological) and biochemical markers.

Official Title
-----------------
Comparison of a Novel Condensed Heat Acclimation Programme With a Traditional Longer-term Heat Acclimation Programme

Conditions
-----------------
Heat Stress

Intervention / Treatment
-----------------
* Other: Heat acclimation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male Physically active and healthy as determined by pre-participation health screening questionnaire. Free of COVID-19 symptoms (loss or change in sense of smell or taste, fever and new, continuous cough) as determined by pre-screening questionnaire. Resting diastolic blood pressure between 60 and 90 mmHg; resting systolic blood pressure between 90 and 150 mmHg A resting ECG is required if: individuals are over 30 years of age; they are unfamiliar with exercise of a maximal nature; they have a family history of adverse cardiac events. The ECG is to be reviewed by the Independent Medical Officer. Exclusion Criteria: Current smokers Recent (< 3 months) participation in a formal heat acclimation regimen, or regular frequent heat exposures that may render the participant partially heat acclimated (other than regular exercise) Recent (< 3 months) high altitude (>1 500m ) sojourn that may render the participant partially altitude acclimated Diagnosed cardiovascular, metabolic or respiratory conditions (excluding asthma) Prior history of heat illness Prior history of collapse or intolerance with exposure to altitude Recent blood donation (within 3 months of commencing study) Baseline serum sodium level <135 mmol.L-1 Any other extant medical condition which may be exacerbated by participation Participants with inadequate understanding of English. Any volunteers who are currently participating in any other research studies which may influence their responses or the results obtained

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel groups design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Traditional heat acclimation<br>The traditional heat acclimation programme will consist of daily 75-minute heat exposures for eight consecutive days | Other: Heat acclimation<br>* Repeated heat exposures with light exercise sufficient to elevate deep body temperature to   38.5C<br>|
| Experimental: Condensed heat acclimation<br>The condensed heat acclimation programme will consist of two consecutive days with four, 75-minute heat exposures undertaken on each day | Other: Heat acclimation<br>* Repeated heat exposures with light exercise sufficient to elevate deep body temperature to   38.5C<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in the peak deep body temperature | Rectal temperature measurement during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in the resting deep body temperature | Rectal temperature measurement during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Reduction in the peak mean body temperature | Weighted rectal and mean skin temperature measurement during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Reduction in the resting mean body temperature | Weighted rectal and mean skin temperature measurement during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased plasma volume | Change in plasma volume calculated from resting haemoglobin and haematocrit prior to a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased sweating rate | Sweating rate calculated from change in nude body mass and accounting for fluid consumption during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Reduced sweat sodium concentration | Sweating sodium concentration assessed from sweat collected in a custom sweat patch on the back during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Reduced exercise heart rate | Heart rate measured using chest telemetry during a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased resting intracellular heat shock protein 70 content | Assessed in peripheral blood mononuclear cells obtained before a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased post heat stress intracellular heat shock protein 70 content | Assessed in peripheral blood mononuclear cells obtained after a heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased resting intracellular heat shock protein 90 alpha content | Assessed in peripheral blood mononuclear cells obtained before a heat stress tests | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Increased post heat stress intracellular heat shock protein 90 alpha content | Assessed in peripheral blood mononuclear cells obtained after a heat stress tests | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Maximal oxygen uptake | Highest rate of oxygen uptake during graded cycling exercise | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Lactate threshold | Power output at 4 mmol.L-1 blood lactate during graded cycling exercise | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Gross mechanical efficiency | Percentage ratio of external work achieved compared to the total energy expenditure during graded cycling exercise below the lactate threshold | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Peak power output | Highest power output achieved during exhaustive cycling exercise | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Peripheral oxygen saturation during exposure to hypoxia | Assessed using ear or finger tip pulse oximetry during a hypoxic tolerance test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Heart rate during exposure to hypoxia | Assessed using chest telemetry during a hypoxic tolerance test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Minute ventilation during exposure to hypoxia | Expire volume of air per minute during a hypoxic tolerance test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Plasma neutrophil gelatinase-associated lipocalin | Concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Urine neutrophil gelatinase-associated lipocalin | Concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Plasma kidney injury molecule-1 | Concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Urine kidney injury molecule-1 | Concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Tissue inhibitor of metalloproteinase 2 | Urine concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Insulin-like growth factor-binding protein 7 | Urine concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Intestinal fatty acid binding protein | Serum concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Soluble cluster of differentiation 14 | Plasma concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Lipopolysaccharide binding protein | Plasma concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Interleukin-6 | Plasma concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) | 
| Cortisol | Plasma concentration change pre to post heat stress test | Pre heat acclimation intervention (up to 1 week) to post heat acclimation intervention (up to 1 week) |