Comparing Exertional Heat Illness Risk Factors Between Patients and Controls

Study Overview
=================
Brief Summary
-----------------
The arduous nature of military training and operations require personnel to encounter high heat load, e.g., during intense physical exertion, particularly in the heat. These conditions reduce operational effectiveness and expose personnel to a risk of incapacitation and death from exertional heat illness (EHI). The primary aim of this study is to compare putative 'chronic' EHI risk factors between a cohort who have suffered a history of EHI and a control cohort with no EHI history. The secondary aim is to examine the influence of these EHI risk factors on thermoregulation during a standard heat tolerance assessment.

Detailed Description
-----------------
Military training and operations present a risk of incapacitation and death from Exertional Heat Illness (EHI). However, widely accepted EHI risk factors are absent in almost half of all United Kingdom (UK) military EHI cases, indicating that a significant number of EHI cases in military personnel involve alternative risk factors. Risk factors for EHI can been classified along a spectrum ranging from acute (e.g. recent poor sleep) to chronic (e.g. low fitness), with the role of chronic risk factors supported by the observation that individuals who have suffered an EHI are at a substantially increased risk of subsequent EHI. The primary aim of this study is to compare putative 'chronic' EHI risk factors (e.g. composition of gastrointestinal (GI) microbiome, infection and inflammation, trait-like psychological factors) between a cohort who have suffered a history of EHI and a control cohort with no EHI history. The secondary aim is to examine the influence of these EHI risk factors on thermoregulation during a standard heat tolerance assessment.

Official Title
-----------------
Comparison of Novel Putative Risk Factors for Exertional Heat Illness Between a Military Patient Cohort and Matched Control Cohort During Exercise Heat Stress

Conditions
-----------------
Exertional Heat Illness

Intervention / Treatment
-----------------
* Other: Heat Tolerance Assessment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals with a history of EHI: Previous EHI episode Normal resting ECG Male or female 18 - 40 years Control participants: No previous history of EHI Normal resting ECG Male or female 18 - 40 years

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Individuals with a history of EHI<br>Service personnel who have a history of EHI. | Other: Heat Tolerance Assessment<br>* 60-90 minutes exercise in hot (34 °C; 45% R.H.) conditions at 60%VO2max<br>|
| Control participants without a history of EHI<br>Matched control participants with no history of EHI. They will be matched to the experimental group for parameters that are known to influence thermoregulatory responses to exercise heat-stress. Relative aerobic fitness (V̇O2max; ml∙kg-1∙min-1) Body mass (kg) Body surface area (m2) Age Sex | Other: Heat Tolerance Assessment<br>* 60-90 minutes exercise in hot (34 °C; 45% R.H.) conditions at 60%VO2max<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Core temperature | Measured using a rectal thermistor. | At 60 minutes (or test termination if earlier) of Heat Tolerance Assessment | 
| Core temperature | Measured using a rectal thermistor. | Rate of rise from 30 to 60 minutes (or test termination if earlier) of Heat Tolerance Assessment | 
| Diversity of gastrointestinal microbiota | Measured in stool sample. Assessed by alpha diversity score. | Baseline | 
| Diversity of gastrointestinal microbiota | Measured in stool sample. Assessed by beta diversity score. | Baseline | 
| Abundance of gastrointestinal microbiota | Measured in stool sample. Assessed at level of phylum. | Baseline | 
| Detection of sexually transmitted pathogens | Assessed from urine sample. Measured using cobas CT/NG assays. | Baseline | 
| Detection of respiratory pathogens | Assessed from throat swab. Measured using Allplex assays. | Baseline | 
| Detection of gastrointestinal pathogens | Assessed from stool swab. Measured using Allplex. | Baseline | 
| Circulating Interleukin 6 | Measured using ELISA | Baseline | 
| Circulating Interleukin 6 | Measured using ELISA | Post Heat Tolerance Assessment (within 15 minutes of test end) | 
| Circulating C-Reactive Protein | Measured using ELISA | Baseline | 
| Circulating C-Reactive Protein | Measured using ELISA | Post Heat Tolerance Assessment (within 15 minutes of test end) | 
| Circulating Claudin 3 | Measured using ELISA | Baseline | 
| Circulating Claudin 3 | Measured using ELISA | Post Heat Tolerance Assessment (within 15 minutes of test end) | 
| Circulating Zonulin | Measured using ELISA | Baseline | 
| Circulating lipopolysaccharide binding protein | Measured using ELISA | Baseline | 
| Circulating lipopolysaccharide binding protein | Measured using ELISA | Post Heat Tolerance Assessment (within 15 minutes of test end) | 
| Circulating intestinal fatty acid binding protein | Measured using ELISA | Baseline | 
| Circulating intestinal fatty acid binding protein | Measured using ELISA | Post Heat Tolerance Assessment (within 15 minutes of test end) | 
| Gastrointestinal illness symptomology questionnaire | Visual analogue scale (0-10). Higher scores indicate worse symptomology | Baseline | 
| Gastrointestinal illness symptomology questionnaire | Visual analogue scale (0-10). Higher scores indicate worse symptomology | Pre Heat Tolerance Assessment | 
| Gastrointestinal illness symptomology questionnaire | Visual analogue scale (0-10). Higher scores indicate worse symptomology | Immediately post Heat Tolerance Assessment | 
| Respiratory illness symptomology, measured by Jackson common cold questionnaire | Higher scores indicate worse symptomology | Baseline | 
| Sleep quality and quantity, measured by Pittsburgh Sleep Quality Index | Higher scores indicate worse sleep | Baseline -3 days | 
| Motivation, measured by Motivation scale |  | Baseline -3 days | 
| State-trait anxiety, measured by state-trait anxiety inventory form Y-2 |  | Baseline -3 days | 
| Risk taking, measured by the risk-taking inventory |  | Baseline -3 days | 
| Resilience, measured by the Connor-Davidson resilience scale |  | Baseline -3 days | 
| Stress, measured by perceived stress scale |  | Baseline -3 days | 
| Mental readiness | Visual analogue scale (0-100). Higher scores indicate a lower state of mental readiness. | Baseline | 
| Stress | Visual analogue scale (0-100). Higher scores indicate a greater state of stress. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat rate |  | At 5 minute intervals during the Heat Tolerance Assessment | 
| Thermal comfort | Modified 9 point Gagge scale. Higher scores indicate worse comfort. | At 15 minute intervals during Heat Tolerance Assessment | 
| Thermal sensation | Modified 9 point Gagge scale. Higher scores indicate hotter sensation | At 15 minute intervals during Heat Tolerance Assessment | 
| Rating of Perceived Exertion | 6-20 Borg scale. Higher scores indicate higher perceived exertion | At 15 minute intervals during Heat Tolerance Assessment | 
| Skin Temperature | Weighted mean skin temperature | During Heat Tolerance Assessment | 
| Sweat rate | Determined from change in nude body mass during the heat tolerance assessment | During Heat Tolerance Assessment |