Clinical trial NCT05678738: Acquiring and Targeting Heat Exposures Necessary for Action
Official title: Enhancing Lethality by Targeting Cognitive and Physiological Mechanisms of Female Warfighter Resiliency to Consecutive Days of Intense Exercise in the Heat
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heat Intolerance
Heat Stress
Fatigue; Heat
Keywords: Sex Differences
Physical Performance
Body Composition
Heat Acclimation
Lead sponsor: University of Connecticut
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2023-01-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will consist of both male and female subjects who will be exposed to similar bouts of exertional heat stress. Analysis will be completed to assess for potential sex-based differences in outcomes measured (male vs. female). Participants (both male and female) who opt-in for antioxidant berry supplementation will be assigned to a subgroup parallel study model where subjects will be exposed to similar bouts of exertional heat stress while consuming either the antioxidant or placebo supplement.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research study is to better understand ways that women and men differ physiologically, cognitively, physically, and cellularly to better prescribe helpful interventions that will prevent injury and risk of conditions like exertional heat illnesses or heatstroke. The main questions this project aims to answer are:

1. What is the relative stress contributing to performance differences between women and men during intense exercise in extremely hot and humid environments in response to exertional heat stress?
2. What is the relative contribution of responses in adipose tissue, cardiovascular tissue, gut microbiota, and musculoskeletal tissue on heat tolerance in women (vs. men) to exertional heat stress?
3. What is the impact of adding an antioxidant juice consumption regime and will it assist in enhancing performance during an acute bout of exercise-heat stress before and after heat acclimation?

Subjects enrolled and approved for participation will perform:

1. a heat acclimation protocol which includes the completion of 5 days of prescribed exercise-heat exposure
2. two separate acute exercise-heat exposures for the assessment of thermotolerance and the investigation of potential enhancements in thermoregulatory performance that may occur after the completion of a 5-day heat acclimation protocol
3. a subset of subjects enrolled and approved for participation who opt in to antioxidant berry supplement consumption will either consume the active or placebo product throughout their participation.


Eligibility criteria: Inclusion Criteria:

* Participants will be healthy men and women, aged 18-50 years, who speak and read the English language fluently. This is required because some of the cognitive tests test grammatical reasoning and offer directional cues recorded as audio files in English. VO2max tests will provide evidence of level of aerobic fitness required to participate in this study. The investigators will use ≥45 ml·kg-1·min-1 for male participants, ≥40 ml·kg-1·min-1 for female participants as our threshold for inclusion.
* The target composition of our subject sample is 50% men and 50% women.
* No difficulties with vision, hearing, or ability to read a computer screen and operate a computer keyboard and mouse.

Exclusion Criteria:

* unable to visit the laboratory on the required, consistent schedule and consecutive required days (Days 2 and 3, Days 12 and 13)
* any contraindications to participating in exercise lasting 60-120 minutes daily during a period of 2 consecutive days, 5 days within an 8-day period, and 2 additional days (if subjects elect to participate in the entire study, all options), screening will include resting blood pressure to exclude pre-hypertensive or hypertensive participants (resting BP \> 120 mmHg and 80mmHg systolic and diastolic, respectively)
* any contraindications to exposure to exercise-heat stress (e.g., medications that affect thermoregulation, family or personal history of issues with anesthetics that indicate possible susceptibility to malignant hyperthermia, evidence of past heat intolerance)
* tobacco use or electronic cigarettes (e-cigarettes) within the past 6 months
* chronic illness (including diabetes, metabolic syndrome, thyroid disease, for example) or other chronic illnesses that make it unsafe for participants to participate in daily rigorous exercise in the heat
* regular supplementation with blood thinners, including the use of aspirin
* acute illness (e.g., influenza, head cold, gastrointestinal illness) during the week of scheduled testing
* current positive COVID-test or infection and past COVID infection within past 6 months
* contraindications to blood draw and if elected to be considered for participation with microdialysis and skeletal muscle biopsy procedures, contraindications to those individual procedures
* for subjects who may not complete a DXA scan, history of claustrophobia
* history of allergic reactions to medical tape and/or latex
* currently participating in "non-traditional" diets including diets such as intermittent fasting, caloric restriction, highly limited consumption of large food classes (e.g., vegan)
* consumption of antioxidant supplementation on a regular, long-term basis outside of the aronia supplementation regime for the study
* limited decision-making ability
* inability to participate in extended physical activity on a treadmill (i.e., standing, running, jogging, walking)
* consumption of a non-traditional diet including diets such as intermittent fasting, caloric restriction, highly limited consumption of large food classes (e.g., vegan) (this includes individuals who are suffering with current diagnosed or undiagnosed eating disorder)
* allergy to povidone, ethyl chloride, lidocaine, or bacitracin
* pregnant or positive pregnancy test during DXA pre-procedures (see DXA SOP)
* allergy to aronia berries, monkfruit, or sham juice ingredients

Primary outcomes:
measure: Change in Rectal Temperature at Rest
timeFrame: Through study completion, an average of 14 days
measure: Change in Rectal Temperature Rate of Rise
timeFrame: Through study completion, an average of 14 days
measure: Change in Rectal Temperature at Thermal Threshold (38.5C)
timeFrame: Measured throughout 5 90-minute exercise-heat stress bouts (heat acclimation sessions)
measure: Change in Mean Skin Temperature
timeFrame: Through study completion, an average of 14 days
measure: Change in Heart Rate
timeFrame: Through study completion, an average of 14 days
measure: Change in Heart Rate at Thermal Threshold (38.5C)
timeFrame: Measured throughout 5 90-minute exercise-heat stress bouts (heat acclimation sessions)
measure: Change in Whole Body Sweat Rate
timeFrame: Measured at the beginning and end of 5 90-minute exercise-heat stress bouts (heat acclimation sessions)
measure: Change in Sweat Metabolite and Protein Expression
timeFrame: Measurement completed during each exercise-heat stress bout (Heat Tolerance Tests 1 [days 5 and 12] and 2 [days 6 and 13]) both before and immediately after heat acclimation as well as the final heat acclimation session (HA5 - day 11)
measure: Change in Cognitive Measures - Visual Vigilance
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Psychomotor Vigilance
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Four Choice Task
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Match to Sample
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Repeated Acquisition
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Grammatical Reasoning
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Profile of Mood States
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Cognitive Measures - Stroop Task
timeFrame: Measurement completed immediately after one exercise-heat stress bout (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Anaerobic Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Agility Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Upper Body Strength Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Lower Body Power Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Lower Body Kinematic Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Physical Performance - Balance Performance
timeFrame: Measurements completed immediately after the cognitive battery performed during the Heat Tolerance Test 2 (days 6 and 13) both before and immediately after heat acclimation
measure: Change in Musculoskeletal Gene and Protein Expression
timeFrame: Measurement completed after the performance of an exercise-heat stress bout and physical performance battery (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Musculoskeletal Fiber-Typing
timeFrame: Measurement completed after the performance of an exercise-heat stress bout and physical performance battery (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Musculoskeletal Mitochondrial Function
timeFrame: Measurement completed after the performance of an exercise-heat stress bout and physical performance battery (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Subcutaneous Abdominal Tissue (SCAAT) Lipolysis Rate
timeFrame: Measurement completed after the performance of an exercise-heat stress bout and physical performance battery (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Resting Energy Expenditure and Macronutrient Oxidation
timeFrame: Measurement completed after the performance of an exercise-heat stress bout and physical performance battery (Heat Tolerance Test 2 - days 6 and 13) both before and immediately after heat acclimation
measure: Change in Circulatory Indicators of Lipid Metabolism - NEFAs
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Lipid Metabolism - Insulin
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Lipid Metabolism - IGF-1
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Stress - Epinephrine
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Stress - Norepinephrine
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Stress - Cortisol
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory RNA Content
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Circulatory Indicators of Inflammation - IL-1B
timeFrame: Measurement completed during the completion of exercise-heat stress bouts (Heat Tolerance Tests 1 [days 5 and 12] and 2 [days 6 and 13]) both before and immediately after heat acclimation
measure: Change in Circulatory Indicators of Inflammation - TNF-a
timeFrame: Measurement completed during the completion of exercise-heat stress bouts (Heat Tolerance Tests 1 [days 5 and 12] and 2 [days 6 and 13]) both before and immediately after heat acclimation
measure: Change in Circulatory Indicators of Inflammation - IFN-gamma
timeFrame: Measurement completed during the completion of exercise-heat stress bouts (Heat Tolerance Tests 1 [days 5 and 12] and 2 [days 6 and 13]) both before and immediately after heat acclimation
measure: Change in Gut Microbiome Diversity
timeFrame: Measurement completed prior to the completion of an exercise-heat stress bout (Heat Tolerance Test 2) both before and after heat acclimation
measure: Change in Saliva Metabolite Expression
timeFrame: Measurement completed during each exercise-heat stress bout (Heat Tolerance Tests 1 and 2) both before and after heat acclimation as well as the final heat acclimation session (HA5)
measure: Change in Thermal Sensation
timeFrame: Through study completion, an average of 14 days
measure: Change in Recovery
timeFrame: Throughout study completion, an average of 14 days
Secondary outcomes:
measure: Change in Perception of Fatigue
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Perception of Thirst
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Environmental Perception
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Rating of Perceived Exertion
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Sleep Quality
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Body Mass
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Reproductive Hormone State - Estradiol
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Reproductive Hormone State - Progesterone
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Reproductive Hormone State - Testosterone
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Reproductive Hormone State - LH
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Reproductive Hormone State - FSH
timeFrame: Throughout study completion, an average of 14 days
measure: Change in Cardiovascular Response - Blood Pressure
timeFrame: Throughout study completion, an average of 14 days
Other outcomes:
Locations:
city: Storrs
country: United States
facility: Human Performance Laboratory at the University of Connecticut
state: Connecticut
Study officials:
affiliation: Korey Stringer Institute - UConn
name: Douglas J Casa, PhD
role: PRINCIPAL_INVESTIGATOR
References: