xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05963529</url>
    </required_header>
    <id_info>
      <org_study_id>uORamp</org_study_id>
      <nct_id>NCT05963529</nct_id>
    </id_info>
    <brief_title>Validity of Humidity Ramp Protocols for Identifying Limits of Survivability in Heat-exposed Persons</brief_title>
    <official_title>Evaluating the Validity of a Rapid Humidity Ramp Protocol for Identifying the Upper Environmental Limits of Thermal Compensation in Humans</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Ottawa</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Ottawa</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The global populace is at growing risk of heat-related illness due to climate change and&#xD;
        accompanying increases in the intensity and regularity of extremely hot temperatures. In&#xD;
        heat-exposed persons, heat gain from the environment and metabolism initially exceeds the&#xD;
        rate of heat dissipation from the skin. Heat is stored in the body, causing core and skin&#xD;
        temperatures to rise, which in turn triggers autonomically mediated elevations in cutaneous&#xD;
        blood flow and sweating to facilitate heat loss. If conditions are compensable, heat loss&#xD;
        increases until it balances total heat gain. At this point, the rate of heat storage falls to&#xD;
        zero (i.e., heat balance is achieved) and body temperature stabilizes, albeit at a level&#xD;
        elevated from thermoneutral conditions. If, however, the maximal achievable rate of heat&#xD;
        dissipation is insufficient to offset heat gain, conditions are uncompensable, and prolonged&#xD;
        exposure will cause a continual rise in core temperature that can compromise health if left&#xD;
        unchecked. The environmental limits of compensability (i.e., the temperatures/humidities&#xD;
        above which heat balance can not be maintained) are therefore an important determinant of&#xD;
        survival during prolonged heat exposure. Evaluating this limit and how it can be modified&#xD;
        (e.g., by behavior or individual factors like age or sex) is an increasingly important and&#xD;
        active field of study.&#xD;
  &#xD;
        Contemporary evaluations of the environmental limits of compensability utilize &quot;ramping&#xD;
        protocols&quot; in which participants are exposed to increasing levels of temperature or humidity&#xD;
        (in 5-10 min stages) while core temperature is monitored. It is generally observed that core&#xD;
        temperature is relatively stable (or rises slightly) in the early stages of exposure but&#xD;
        undergoes an abrupt and rapid increase as heat stress becomes more severe. The conditions&#xD;
        (e.g., wet-bulb temperature or wet-bulb globe temperature) at this &quot;inflection point&quot; are&#xD;
        taken as the limits of compensability. That is, it is assumed that inflection corresponds to&#xD;
        the demarcation point, below which core temperature would remain stable for prolonged periods&#xD;
        (theoretically indefinitely if hydration is maintained) but above which heat loss is&#xD;
        insufficient to offset heat gain, causing core temperature to rise continuously. Despite the&#xD;
        increasing use of these protocols, no study has clearly demonstrated their validity for&#xD;
        identifying the environmental limits of compensability. The goal of this project is therefore&#xD;
        to assess the validity of ramping protocols for determining the ambient conditions above&#xD;
        which thermal compensation is not possible.&#xD;
  &#xD;
        Enrolled participants will complete four experimental trials in a climate-controlled chamber:&#xD;
        one ramping protocol followed by three randomized fixed-condition exposures. In the ramping&#xD;
        protocol, participants will rest in 42°C with 28% relative humidity (RH) for 70 min, after&#xD;
        which RH will be increased 3% every 10 min until 70% RH is achieved. The core (esophageal)&#xD;
        temperature inflection point will be determined. For the fixed-condition exposures,&#xD;
        participants will rest in i) 42°C with RH ~5% below their individual inflection point&#xD;
        (below-inflection condition), ii) 42°C with RH ~5% above their individual inflection point&#xD;
        (above-inflection condition), and iii) 26°C with 45% RH (control condition). Comparing the&#xD;
        rate of change in esophageal temperature between each fixed-condition exposure will provide&#xD;
        important insight into the validity of ramping protocols for identifying the limits of&#xD;
        compensability.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 14, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2023</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Each participant will complete four trial conditions including one humidity-ramp protocol and three fixed-condition exposures. The humidity ramp protocol will always be completed first. Ambient temperature will remain constant at 42°C. After a 1-hour equilibrium period, relative humidity will be increased by 3% in 10-min increments, from 28% to 70%. The inflection point for core (esophageal) temperature will be subsequently determined.&#xD;
  On three separate days following the humidity ramp protocol, participants will complete three fixed-condition exposures in random order: 1) 42°C with relative humidity &gt;5% below the estimate compensability limit (below-threshold condition); 2) 42°C with relative humidity &gt;5% above the estimated compensability limit (above-threshold condition) and 3) 28°C with 35% relative humidity (control condition). Exposure will be terminated early if core temperature exceeds 39.2°C or if the participant requests to withdraw.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Participants will be informed of the study interventions before providing informed consent but will be masked to the order the fixed-condition exposures (i.e., participants will not know whether the humidity is above or below their identified inflection point). Data processing and statistical analysis for the fixed-condition exposures will be performed with the analyst blinded to participant and trial conditions.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Esophageal temperature rate of change</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Rate of change of esophageal temperature measured over the final 2-hours of heat exposure</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Predicted time until 40.2°C esophageal temperature</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Estimated time for esophageal temperature to reach 40.2°C, a commonly-cited criteria for severe heat-illness (e.g., heat stroke), calculated from the end-exposure esophageal temperature and its rate of change (assuming this rate of change is sustained)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Rectal temperature rate of change</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Rate of change of rectal temperature measured over the final 2-hours of heat exposure</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Predicted time until 40.2°C rectal temperature</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Estimated time for rectal temperature to reach 40.2°C, a commonly-cited criteria for</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants unable to finish fixed-condition heat exposure</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Number of participants who could not complete each fixed-condition heat exposure due to participant withdrawal or achieving a core temperature of 39.5°C</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean skin temperature rate of change</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Rate of change of skin temperature measured over the final 2-hours of heat exposure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate rate of change</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Rate of change of heart rate measured over the final 2-hours of heat exposure</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Esophageal temperature</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Esophageal temperature at the end of the fixed-condition exposures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rectal temperature</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Rectal temperature at the end of the fixed-condition exposures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean skin temperature</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Mean skin temperature at the end of the fixed-condition exposures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Heart rate</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Heart rate at the end of the fixed-condition exposures</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Thermal sensation</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Self-reported thermal sensation at the end of the fixed-condition exposures using and 8-point scale ranging from neutral (0) to extremely hot (8).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sweat rate</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Sweat rate at the end of the fixed-condition exposures (calculated via change in body weight)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Net fluid loss</measure>
      <time_frame>End of fixed-condition heat exposure (hour 9 or termination)</time_frame>
      <description>Net fluid loss estimated as the percentage change in body mass over the fixed-condition exposures.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Esophageal temperature inflection point</measure>
      <time_frame>During the ramp protocol (up to 2.5 hours)</time_frame>
      <description>Inflection point for esophageal temperature during the humidity-ramp protocol</description>
    </other_outcome>
    <other_outcome>
      <measure>Rectal temperature inflection point</measure>
      <time_frame>During the ramp protocol (up to 2.5 hours)</time_frame>
      <description>Inflection point for rectal temperature during the humidity-ramp protocol</description>
    </other_outcome>
    <other_outcome>
      <measure>Heart rate inflection point</measure>
      <time_frame>During the ramp protocol (up to 2.5 hours)</time_frame>
      <description>Inflection point for heart rate during the humidity-ramp protocol</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Heat Stress</condition>
    <condition>Heat Exposure</condition>
    <condition>Temperature Change, Body</condition>
    <condition>Temperature; Extreme, Exposure</condition>
    <arm_group>
      <arm_group_label>Humidity-ramp protocol</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Above-inflection fixed-condition exposure</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Below-inflection fixed-condition exposure</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control fixed-condition exposure</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Humidity-ramp protocol</intervention_name>
      <description>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 esophageal temperature (and rectal temperature and heart rate) inflect is subsequently determined.</description>
      <arm_group_label>Humidity-ramp protocol</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Above-inflection fixed-condition exposure</intervention_name>
      <description>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' individual 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.</description>
      <arm_group_label>Above-inflection fixed-condition exposure</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Below-inflection fixed-condition exposure</intervention_name>
      <description>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 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.</description>
      <arm_group_label>Below-inflection fixed-condition exposure</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Control fixed-condition exposure</intervention_name>
      <description>Participants are exposed for 9-hours to 28°C with 35% relative humidity. Participant will be allowed to drink tap water ad libitum.</description>
      <arm_group_label>Control fixed-condition exposure</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female adults.&#xD;
  &#xD;
            -  Aged 18-85 years.&#xD;
  &#xD;
            -  Non-smoking.&#xD;
  &#xD;
            -  English or French speaking.&#xD;
  &#xD;
            -  Ability to provide informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Physical restriction (e.g., due to disease: intermittent claudication, renal&#xD;
               impairment, active proliferative retinopathy, unstable cardiac or pulmonary disease,&#xD;
               disabling stroke, severe arthritis, etc.).&#xD;
  &#xD;
            -  Use of or changes in medication judged by the patient or investigators to make&#xD;
               participation in this study inadvisable (e.g., medications increasing risk of&#xD;
               heat-related illness; beta blockers, anticholinergics, etc.)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Robert D Meade, PhD, MPH</last_name>
      <role>Study Director</role>
      <affiliation>University of Ottawa</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Glen P Kenny, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Ottawa</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Robert D Meade, PhD, MPH</last_name>
      <phone>1=613-698-6071</phone>
      <email>rmead015@uottawa.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Glen P Kenny, PhD</last_name>
      <phone>1-613-562-5800</phone>
      <phone_ext>4282</phone_ext>
      <email>gkenny@uottawa.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Ottawa</name>
        <address>
          <city>Ottawa</city>
          <state>Ontario</state>
          <zip>K1N6N5</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Glen P Kenny, PhD</last_name>
        <phone>1613-562-5800</phone>
        <phone_ext>4282</phone_ext>
        <email>gkenny@uottawa.ca</email>
      </contact>
      <contact_backup>
        <last_name>Robert D Meade, PhD</last_name>
        <phone>16136986071</phone>
        <email>rmead015@uottawa.ca</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Ottawa</investigator_affiliation>
      <investigator_full_name>Glen P. Kenny</investigator_full_name>
      <investigator_title>Full Professor</investigator_title>
    </responsible_party>
    <keyword>Heat wave</keyword>
    <keyword>Hot weather</keyword>
    <keyword>Heat strain</keyword>
    <keyword>Cardiovascular strain</keyword>
    <keyword>Environmental limits for compensability</keyword>
    <keyword>Extreme heat events</keyword>
    <keyword>Heat survivability</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Body Temperature Changes</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified participant data will be made available upon reasonable request and signed access agreement.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Data will be made available following publication of the primary study report.</ipd_time_frame>
      <ipd_access_criteria>Reasonable request and signed access agreement</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05963529
  org study id: uORamp
  nct id: NCT05963529
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The global populace is at growing risk of heat-related illness due to climate change and
        accompanying increases in the intensity and regularity of extremely hot temperatures. In
        heat-exposed persons, heat gain from the environment and metabolism initially exceeds the
        rate of heat dissipation from the skin. Heat is stored in the body, causing core and skin
        temperatures to rise, which in turn triggers autonomically mediated elevations in cutaneous
        blood flow and sweating to facilitate heat loss. If conditions are compensable, heat loss
        increases until it balances total heat gain. At this point, the rate of heat storage falls to
        zero (i.e., heat balance is achieved) and body temperature stabilizes, albeit at a level
        elevated from thermoneutral conditions. If, however, the maximal achievable rate of heat
        dissipation is insufficient to offset heat gain, conditions are uncompensable, and prolonged
        exposure will cause a continual rise in core temperature that can compromise health if left
        unchecked. The environmental limits of compensability (i.e., the temperatures/humidities
        above which heat balance can not be maintained) are therefore an important determinant of
        survival during prolonged heat exposure. Evaluating this limit and how it can be modified
        (e.g., by behavior or individual factors like age or sex) is an increasingly important and
        active field of study.
  
        Contemporary evaluations of the environmental limits of compensability utilize "ramping
        protocols" in which participants are exposed to increasing levels of temperature or humidity
        (in 5-10 min stages) while core temperature is monitored. It is generally observed that core
        temperature is relatively stable (or rises slightly) in the early stages of exposure but
        undergoes an abrupt and rapid increase as heat stress becomes more severe. The conditions
        (e.g., wet-bulb temperature or wet-bulb globe temperature) at this "inflection point" are
        taken as the limits of compensability. That is, it is assumed that inflection corresponds to
        the demarcation point, below which core temperature would remain stable for prolonged periods
        (theoretically indefinitely if hydration is maintained) but above which heat loss is
        insufficient to offset heat gain, causing core temperature to rise continuously. Despite the
        increasing use of these protocols, no study has clearly demonstrated their validity for
        identifying the environmental limits of compensability. The goal of this project is therefore
        to assess the validity of ramping protocols for determining the ambient conditions above
        which thermal compensation is not possible.
  
        Enrolled participants will complete four experimental trials in a climate-controlled chamber:
        one ramping protocol followed by three randomized fixed-condition exposures. In the ramping
        protocol, participants will rest in 42°C with 28% relative humidity (RH) for 70 min, after
        which RH will be increased 3% every 10 min until 70% RH is achieved. The core (esophageal)
        temperature inflection point will be determined. For the fixed-condition exposures,
        participants will rest in i) 42°C with RH ~5% below their individual inflection point
        (below-inflection condition), ii) 42°C with RH ~5% above their individual inflection point
        (above-inflection condition), and iii) 26°C with 45% RH (control condition). Comparing the
        rate of change in esophageal temperature between each fixed-condition exposure will provide
        important insight into the validity of ramping protocols for identifying the limits of
        compensability.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Each participant will complete four trial conditions including one humidity-ramp protocol and three fixed-condition exposures. The humidity ramp protocol will always be completed first. Ambient temperature will remain constant at 42°C. After a 1-hour equilibrium period, relative humidity will be increased by 3% in 10-min increments, from 28% to 70%. The inflection point for core (esophageal) temperature will be subsequently determined.
  On three separate days following the humidity ramp protocol, participants will complete three fixed-condition exposures in random order: 1) 42°C with relative humidity >5% below the estimate compensability limit (below-threshold condition); 2) 42°C with relative humidity >5% above the estimated compensability limit (above-threshold condition) and 3) 28°C with 35% relative humidity (control condition). Exposure will be terminated early if core temperature exceeds 39.2°C or if the participant requests to withdraw.
  primary purpose: Basic Science
  masking: Double (Participant, Outcomes Assessor)
  masking description: Participants will be informed of the study interventions before providing informed consent but will be masked to the order the fixed-condition exposures (i.e., participants will not know whether the humidity is above or below their identified inflection point). Data processing and statistical analysis for the fixed-condition exposures will be performed with the analyst blinded to participant and trial conditions.
  measure: Esophageal temperature rate of change
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Rate of change of esophageal temperature measured over the final 2-hours of heat exposure
  measure: Predicted time until 40.2°C esophageal temperature
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Estimated time for esophageal temperature to reach 40.2°C, a commonly-cited criteria for severe heat-illness (e.g., heat stroke), calculated from the end-exposure esophageal temperature and its rate of change (assuming this rate of change is sustained)
  measure: Rectal temperature rate of change
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Rate of change of rectal temperature measured over the final 2-hours of heat exposure
  measure: Predicted time until 40.2°C rectal temperature
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Estimated time for rectal temperature to reach 40.2°C, a commonly-cited criteria for
  measure: Number of participants unable to finish fixed-condition heat exposure
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Number of participants who could not complete each fixed-condition heat exposure due to participant withdrawal or achieving a core temperature of 39.5°C
  measure: Mean skin temperature rate of change
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Rate of change of skin temperature measured over the final 2-hours of heat exposure
  measure: Heart rate rate of change
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Rate of change of heart rate measured over the final 2-hours of heat exposure
  measure: Esophageal temperature
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Esophageal temperature at the end of the fixed-condition exposures
  measure: Rectal temperature
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Rectal temperature at the end of the fixed-condition exposures
  measure: Mean skin temperature
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Mean skin temperature at the end of the fixed-condition exposures
  measure: Heart rate
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Heart rate at the end of the fixed-condition exposures
  measure: Thermal sensation
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Self-reported thermal sensation at the end of the fixed-condition exposures using and 8-point scale ranging from neutral (0) to extremely hot (8).
  measure: Sweat rate
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Sweat rate at the end of the fixed-condition exposures (calculated via change in body weight)
  measure: Net fluid loss
  time frame: End of fixed-condition heat exposure (hour 9 or termination)
  description: Net fluid loss estimated as the percentage change in body mass over the fixed-condition exposures.
  measure: Esophageal temperature inflection point
  time frame: During the ramp protocol (up to 2.5 hours)
  description: Inflection point for esophageal temperature during the humidity-ramp protocol
  measure: Rectal temperature inflection point
  time frame: During the ramp protocol (up to 2.5 hours)
  description: Inflection point for rectal temperature during the humidity-ramp protocol
  measure: Heart rate inflection point
  time frame: During the ramp protocol (up to 2.5 hours)
  description: Inflection point for heart rate during the humidity-ramp protocol
  arm group label: Humidity-ramp protocol
  arm group type: Other
  description: Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.
  arm group label: Above-inflection fixed-condition exposure
  arm group type: Experimental
  description: Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.
  arm group label: Below-inflection fixed-condition exposure
  arm group type: Experimental
  description: Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.
  arm group label: Control fixed-condition exposure
  arm group type: Active Comparator
  description: Healthy male and female volunteers. Participants will complete all exposures. The humidity-ramp protocol will necessarily be performed first. The order of the fixed-condition exposures will be randomized.
  intervention type: Other
  intervention name: Humidity-ramp protocol
  description: 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 esophageal temperature (and rectal temperature and heart rate) inflect is subsequently determined.
  arm group label: Humidity-ramp protocol
  intervention type: Other
  intervention name: Above-inflection fixed-condition exposure
  description: 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' individual 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.
  arm group label: Above-inflection fixed-condition exposure
  intervention type: Other
  intervention name: Below-inflection fixed-condition exposure
  description: 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 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.
  arm group label: Below-inflection fixed-condition exposure
  intervention type: Other
  intervention name: Control fixed-condition exposure
  description: Participants are exposed for 9-hours to 28°C with 35% relative humidity. Participant will be allowed to drink tap water ad libitum.
  arm group label: Control fixed-condition exposure
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Robert D Meade, PhD, MPH
  role: Study Director
  affiliation: University of Ottawa
  last name: Glen P Kenny, PhD
  role: Principal Investigator
  affiliation: University of Ottawa
  last name: Robert D Meade, PhD, MPH
  phone: 1=613-698-6071
  email: rmead015@uottawa.ca
  last name: Glen P Kenny, PhD
  phone: 1-613-562-5800
  phone ext: 4282
  email: gkenny@uottawa.ca
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: Canada
  responsible party type: Principal Investigator
  investigator affiliation: University of Ottawa
  investigator full name: Glen P. Kenny
  investigator title: Full Professor
  mesh term: Body Temperature Changes
  sharing ipd: Yes
  ipd description: De-identified participant data will be made available upon reasonable request and signed access agreement.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Analytic Code
  ipd time frame: Data will be made available following publication of the primary study report.
  ipd access criteria: Reasonable request and signed access agreement