Identifying the Limits of Survivability in Heat-exposed Older Females

NCT07032493 | Recruiting

• 1 other identifier: HEPRU-2025-05-A
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

Climate change increases extreme heat events, elevating global heat-illness risk. Females have reduced heat loss capacity (\~5%) compared to males, driven by differences in skin blood flow and sweating responses. While findings on sex-mediated mortality are mixed, some studies suggest older females (≥65 years), face higher heat-related mortality/morbidity risks, evidenced by disproportionate female deaths in the 2021 Western Heat Dome. The effects of extreme uncompensable heat on older females remain understudied. Heat exposure initially causes net heat gain, raising core/skin temperatures and triggering heat-loss responses. Under compensable heat stress, heat loss balances gain, stabilizing core temperature. Uncompensable heat stress (exceeding maximal dissipation capacity) causes continuous core temperature rise, posing severe health risks. The specific temperature and relative humidity (RH) limits where compensability is lost are critical survival determinants, influenced by age and sex. Ramping protocols identify these limits: participants face progressively increasing heat stress (e.g., staged humidity rises) while core temperature is monitored. Core temperature typically stabilizes initially, then exhibits an abrupt rapid increase at an inflection point, operationally defined as the limit of compensability. Despite increasing use, ramping protocol validity for accurately identifying this threshold remains unverified. This project assesses ramping protocol validity for determining uncompensable conditions in older females and evaluates cumulative thermal and cardiovascular strain, as well as psychological and cognitive responses to both uncompensable and compensable heat. Participants will complete five trials. Trial 1 (Ramping): Rest at 42°C, 28% RH for 70min, then incremental RH increases (3% every 10min) to 70% RH. Individual core temperature (rectal) inflection points are identified from the ramping trial. Trials 2-5 (Fixed Conditions, Randomized): i) \~10% below inflection; ii) \~5% below inflection; iii) \~5% above inflection; iv) Thermo-neutral control (26°C, 45% RH). Comparing the rate of rectal temperature change and cumulative strain during prolonged fixed exposures (especially below vs. above inflection) will validate if the ramping inflection point represents the true limit of compensability for older females.

Conditions

Heat Stress; Temperature Change, Body; Aging; Thermoregulation; Heat Exposure

Keywords

heat strain; women; heat illness; Environmental limits for compensability; heat wave; hot weather; extreme heat events

Outcome Measures

Primary Outcomes (3)

• Rectal temperature rate of change

  Rate of change of rectal temperature measured over the final 2-hours of heat exposure

  End of fixed-condition heat exposure (hour 9 or termination)

• Predicted time until 40.2°C esophageal temperature

  Estimated time for rectal temperature to reach 40.2°C, a commonly-cited criteria for severe heat-illness (e.g., heat stroke), calculated from the end-exposure rectal temperature and its rate of change (assuming this rate of change is sustained)

  End of fixed-condition heat exposure (hour 9 or termination)

• Core temperature (AUC)

  Area under the curve (AUC) of rectal temperature (in degree-hours) measured over the fixed-condition heat exposure

  End of fixed-condition heat exposure (hour 9 or termination)

Secondary Outcomes (10)

• Number of participants unable to finish fixed-condition heat exposure

  End of fixed-condition heat exposure (hour 9 or termination)

• Mean skin temperature rate of change

  End of fixed-condition heat exposure (hour 9 or termination)

• Heart rate rate of change

  End of fixed-condition heat exposure (hour 9 or termination)

• Heart rate (AUC)

  End of fixed-condition heat exposure (hour 9 or termination)

• Thermal sensation

  End of fixed-condition heat exposure (hour 9 or termination)

Other Outcomes (2)

• Rectal temperature inflection point

  During the ramp protocol (up to 2.5 hours)

• Heart rate inflection point

  During the ramp protocol (up to 2.5 hours)

Study Arms (5)

Humidity-ramp protocol

OTHER

The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.

Other: Humidity-Ramp Protocol

Below-inflection fixed-condition heat exposure (5%)

EXPERIMENTAL

Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.

Other: Below-inflection fixed-condition exposure (5%)

Control fixed-condition heat exposure

ACTIVE COMPARATOR

Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.

Other: Control fixed-condition exposure

Below-inflection fixed-condition heat exposure (10%)

EXPERIMENTAL

Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.

Other: Below-inflection fixed-condition exposure (10%)

Above-inflection fixed-condition heat exposure (5%)

EXPERIMENTAL

Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.

Other: Above-inflection fixed-condition exposure (5%)

Interventions

Humidity-Ramp Protocol OTHER

Participants are exposed to 42°C and 28% relative humidity for 70 minutes. Thereafter, humidity is increased 3% until an ambient humidity of 70% is achieved. The humidity at which rectal temperature inflect is subsequently determined.

Humidity-ramp protocol

Above-inflection fixed-condition exposure (5%) OTHER

After a 1 hour equilibrium at 42°C and 28% relative humidity, humidity will be increased 3% every 10 min until it is \~5% higher than the participants' rectal esophageal temperature inflection point identified in the humidity ramp protocol. These conditions will be held constant for the remainder of the 9-hour exposure period (starting from the beginning of equilibrium). Tap water will be provided at regular intervals to limit dehydration.

Above-inflection fixed-condition heat exposure (5%)

Below-inflection fixed-condition exposure (5%) OTHER

After a 1 hour equilibrium at 42°C and 28% relative humidity, humidity will be increased 3% every 10 min until it is \~5% lower than the participants' individual rectal temperature inflection point identified in the humidity ramp protocol. These conditions will be held constant for the remainder of the 9-hour exposure period (starting from the beginning of equilibrium). Tap water will be provided at regular intervals to limit dehydration.

Below-inflection fixed-condition heat exposure (5%)

Below-inflection fixed-condition exposure (10%) OTHER

After a 1 hour equilibrium at 42°C and 28% relative humidity, humidity will be increased 3% every 10 min until it is \~10% lower than the participants' individual rectal temperature inflection point identified in the humidity ramp protocol. These conditions will be held constant for the remainder of the 9-hour exposure period (starting from the beginning of equilibrium). Tap water will be provided at regular intervals to limit dehydration.

Below-inflection fixed-condition heat exposure (10%)

Control fixed-condition exposure OTHER

Participants are exposed for 9-hours to 28°C with 35% relative humidity. Participant will be allowed to drink tap water ad libitum.

Control fixed-condition heat exposure

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Non-smoking.
• English or French speaking.
• Ability to provide informed consent.
• With or without a) chronic hypertension (elevated resting blood pressure; as defined by Heart and Stroke Canada and Hypertension Canada), b) type 2 diabetes as defined by Diabetes Canada, with at least 5 years having elapsed since time of diagnosis

You may not qualify if:

• Episode(s) of severe hypoglycemia (requiring the assistance of another person) within the previous year, or inability to sense hypoglycemia (hypoglycemia unawareness).
• Serious complications related to diabetes (gastroparesis, renal disease, uncontrolled hypertension, severe autonomic neuropathy).
• Uncontrolled hypertension - BP \>150 mmHg systolic or \>95 mmHg diastolic in a sitting position.
• Restrictions in physical activity due to disease (e.g. intermittent claudication, renal impairment, active proliferative retinopathy, unstable cardiac or pulmonary disease, disabling stroke, severe arthritis, etc.).
• Use of or changes in medication judged by the patient or investigators to make participation in this study inadvisable.
• Cardiac abnormalities identified during screening

Sponsors & Collaborators

• University of Ottawa: lead

Study Sites (2)

University of Ottawa

Ottawa, Ontario, K1N6N5, Canada

NOT YET RECRUITING

University of Ottawa

Ottawa, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Heat Stress Disorders; Body Temperature Changes

Condition Hierarchy (Ancestors)

Wounds and Injuries; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Glen P Kenny, PhD

  University of Ottawa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glen P Kenny, PhD

CONTACT

613-562-5800; gkenny@uottawa.ca

Caroline Li-Maloney, MSc

CONTACT

6476187947; cmalo020@uottawa.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: June 14, 2025
• First Posted: June 24, 2025
• Study Start: July 16, 2025
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be made available following publication of the primary study report.
• Access Criteria: Reasonable request and signed access agreement

Locations

CA (2)