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/NCT05990387</url>
    </required_header>
    <id_info>
      <org_study_id>2011690870; Aim 2</org_study_id>
      <nct_id>NCT05990387</nct_id>
    </id_info>
    <brief_title>MIrabegron and Physiological Function in Cold Environments</brief_title>
    <official_title>Mirabegron and Physiological Function in Cold Environments - Aim 1</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Indiana University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Office of Naval Research (ONR)</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>Indiana University</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Many Navy diving operations are performed in cold water. Despite technical advances to&#xD;
        improve thermal protection for cold water diving, these applications are cumbersome and do&#xD;
        not provide complete thermal protection as thermal discomfort is subjectively reported by&#xD;
        many Navy divers. Brown adipose tissue is highly thermogenic in humans. Therefore, activation&#xD;
        of brown adipose tissue might improve cold water tolerance and lower thermal discomfort&#xD;
        during cold water diving operations. Mirabegron is a beta-3-adrenergic receptor agonist that&#xD;
        is used to treat overactive bladder. Beta-3-adrenergic receptors are located on the urinary&#xD;
        bladder, gallbladder and brown adipose tissue. Recent evidence has demonstrated that acute&#xD;
        mirabegron administration increases thermogenesis for ~3 hours in humans. However, it is&#xD;
        currently not known which dose of mirabegron can increase thermogenesis for longer durations.&#xD;
        It is also not known if mirabegron administration can improve cold water tolerance and&#xD;
        thermal discomfort during cold water immersion. Finally, it is not known if mirabegron can&#xD;
        increase thermogenesis during sympathetic stimulation. This project will fill these knowledge&#xD;
        gaps by determining if acute mirabegron administration will delay the fall in core&#xD;
        temperature and the onset of shivering during a progressive cold-water immersion challenge.&#xD;
        This study is part of a collection of studies that will show if mirabegron is a potential&#xD;
        ergogenic aid that can be used to improve cold water tolerance in Navy divers which will&#xD;
        ultimately improve the likelihood of successful missions.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized, double-blind, placebo-controlled, cross-over experimental design.&#xD;
        Participants will be asked to complete 3 visits to the laboratory; one informed&#xD;
        consent/screening visit and 2 study visits. On study visit days, participants will report to&#xD;
        the laboratory following a 12-hour fast, and 24-hour abstention from exercise, caffeine, and&#xD;
        alcohol. During the study visits, participants will ingest either a placebo or one dose of&#xD;
        mirabegron prior to entering our water immersion tank. Then they will be instrumented for the&#xD;
        measurement of heart rate (3-lead ECG), blood pressure (brachial artery auscultation), core&#xD;
        temperature (rectal thermistor), and indices of shivering (surface mechanomyography using&#xD;
        triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh), oxygen&#xD;
        consumption via ventilation and expired gases, and the bedside shivering assessment scale).&#xD;
        Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal&#xD;
        sensation. Following 10 minutes of resting baseline measurements, infrared thermography will&#xD;
        then be used to measure skin temperature of the supraclavicular fossa as an estimate of brown&#xD;
        adipose tissue activation and thermal perceptions will be assessed.&#xD;
  &#xD;
        The measurement of supraclavicular fossa skin temperature (infrared thermography) and thermal&#xD;
        perceptions will be assessed every 10 minutes prior to the progressive cold-water challenge.&#xD;
        After 30 minutes of seated rest, pre-immersion measurements of heart rate, blood pressure,&#xD;
        core temperature, shivering, and thermal perceptions will be conducted and an infrared&#xD;
        thermography image will be taken. Then, the water immersion tank will be filled up to the&#xD;
        participant's neck with 35 degrees C (95 degrees F) water. Heart rate, blood pressure, core&#xD;
        temperature, and shivering indices will be continuously measured. Infrared thermography and&#xD;
        thermal perceptions will be obtained every 5 minutes throughout the progressive cold-water&#xD;
        challenge. The temperature of the water will be progressively lowered by ~12 degrees C every&#xD;
        60 minutes until the water temperature reaches 10 degrees C (50 degrees F) or until the&#xD;
        participant can no longer tolerate the cold or if rectal temperature reaches 35.5 degrees C&#xD;
        (95.9 degrees F). Upon completion of the progressive cold water challenge, the water in the&#xD;
        tank will be rapidly emptied. Participants will gently towel dry and will be able to don a&#xD;
        circulating warm water perfused suit and/or use a mylar blanket to reestablish core&#xD;
        temperature.&#xD;
  &#xD;
        Participants will be asked to return to the laboratory after 10-14 days to repeat the&#xD;
        experiment with the drug assignment not yet received. Each participant's order of assignment&#xD;
        to placebo or drug ingestion (prior to the cold water challenge) over the 2 study visits will&#xD;
        be randomly assigned.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 19, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2023</primary_completion_date>
    <phase>Phase 1/Phase 2</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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Cold temperature deflection point</measure>
      <time_frame>Through session completion, up to 4 hours</time_frame>
      <description>Core temperature will be continuously measured using rectal thermistors. The point at which core temperature begins to fall (i.e., deflection point) will be identified using Prism 8 software by plotting core temperature vs. water temperature.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Thermogenesis - Oxygen Consumption</measure>
      <time_frame>Through session completion, up to 4 hours</time_frame>
      <description>Oxygen consumption is one measure of shivering. A pneumotach connected to a mouthpiece or facemask will be used to measure the flow of inspired and expired air. Expired gases will be sampled using oxygen and carbon dioxide sensors to determine oxygen consumption and carbon dioxide production.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Shivering inflection point - Surface Mechanomyography</measure>
      <time_frame>Through session completion, up to 4 hours</time_frame>
      <description>Surface Mechanomyography is one measure of shivering. Three triaxial accelerometers adhered to the skin using adhesive tape on the chest, upper back, and thigh will be used to assess shivering.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Shivering Inflection point - Bedside Shivering Scale</measure>
      <time_frame>Through session completion, up to 4 hours</time_frame>
      <description>The Bedside Shivering Scale is one measure of shivering. Two investigators will subjectively assess shivering by the participants using a Likert scale (0 = none, 3 = Severe) and the scores will be averaged.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Resting Energy Expenditure</condition>
    <condition>Thermogenesis</condition>
    <condition>Brown Adipose Tissue</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Given once, followed by observation for up to 4 hours in a progressively cold water challenge</description>
    </arm_group>
    <arm_group>
      <arm_group_label>100 mg Mirabegron</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Given once, followed by observation for up to 4 hours in a progressively cold water challenge</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mirabegron</intervention_name>
      <description>Dose-response effect on thermogenesis</description>
      <arm_group_label>100 mg Mirabegron</arm_group_label>
      <other_name>Myrbetriq</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo control condition</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Men and women&#xD;
  &#xD;
            -  18-40 years old&#xD;
  &#xD;
            -  Participate in 150 minutes or more of at least moderate intensity exercise per week&#xD;
               during the previous 2 years&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  diagnosed autonomic disease&#xD;
  &#xD;
            -  diagnosed cardiovascular disease&#xD;
  &#xD;
            -  diagnosed metabolic disease&#xD;
  &#xD;
            -  diagnosed neurologic disease&#xD;
  &#xD;
            -  diagnosed endocrine disease&#xD;
  &#xD;
            -  diagnosed respiratory disease&#xD;
  &#xD;
            -  diagnosed liver dysfunction&#xD;
  &#xD;
            -  diagnosed kidney dysfunction&#xD;
  &#xD;
            -  Women who are pregnant or breastfeeding&#xD;
  &#xD;
            -  Individuals currently taking a medication (with the exception of birth control,&#xD;
               including hormonal contraception) that cannot be safely discontinued for 5 biological&#xD;
               half-lifes prior to each study visit based on consultation with the study physician.&#xD;
  &#xD;
            -  Current tobacco or electronic cigarette use or consistent use within the last 1 year&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Blair D Johnson, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Indiana University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Blair D Johnson, PhD</last_name>
      <phone>8128558699</phone>
      <email>bj33@indiana.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Indiana University</name>
        <address>
          <city>Bloomington</city>
          <state>Indiana</state>
          <zip>47405</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Blair Johnson, PhD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 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>Indiana University</investigator_affiliation>
      <investigator_full_name>Blair D. Johnson, PhD</investigator_full_name>
      <investigator_title>Associate Professor School of Public Health</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mirabegron</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05990387
  org study id: 2011690870; Aim 2
  nct id: NCT05990387
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  Many Navy diving operations are performed in cold water. Despite technical advances to
        improve thermal protection for cold water diving, these applications are cumbersome and do
        not provide complete thermal protection as thermal discomfort is subjectively reported by
        many Navy divers. Brown adipose tissue is highly thermogenic in humans. Therefore, activation
        of brown adipose tissue might improve cold water tolerance and lower thermal discomfort
        during cold water diving operations. Mirabegron is a beta-3-adrenergic receptor agonist that
        is used to treat overactive bladder. Beta-3-adrenergic receptors are located on the urinary
        bladder, gallbladder and brown adipose tissue. Recent evidence has demonstrated that acute
        mirabegron administration increases thermogenesis for ~3 hours in humans. However, it is
        currently not known which dose of mirabegron can increase thermogenesis for longer durations.
        It is also not known if mirabegron administration can improve cold water tolerance and
        thermal discomfort during cold water immersion. Finally, it is not known if mirabegron can
        increase thermogenesis during sympathetic stimulation. This project will fill these knowledge
        gaps by determining if acute mirabegron administration will delay the fall in core
        temperature and the onset of shivering during a progressive cold-water immersion challenge.
        This study is part of a collection of studies that will show if mirabegron is a potential
        ergogenic aid that can be used to improve cold water tolerance in Navy divers which will
        ultimately improve the likelihood of successful missions.
  This is a randomized, double-blind, placebo-controlled, cross-over experimental design.
        Participants will be asked to complete 3 visits to the laboratory; one informed
        consent/screening visit and 2 study visits. On study visit days, participants will report to
        the laboratory following a 12-hour fast, and 24-hour abstention from exercise, caffeine, and
        alcohol. During the study visits, participants will ingest either a placebo or one dose of
        mirabegron prior to entering our water immersion tank. Then they will be instrumented for the
        measurement of heart rate (3-lead ECG), blood pressure (brachial artery auscultation), core
        temperature (rectal thermistor), and indices of shivering (surface mechanomyography using
        triaxial accelerometers at 3 anatomic sites (chest, upper back, and thigh), oxygen
        consumption via ventilation and expired gases, and the bedside shivering assessment scale).
        Thermal perceptions will be assessed using Likert scales for thermal discomfort and thermal
        sensation. Following 10 minutes of resting baseline measurements, infrared thermography will
        then be used to measure skin temperature of the supraclavicular fossa as an estimate of brown
        adipose tissue activation and thermal perceptions will be assessed.
  
        The measurement of supraclavicular fossa skin temperature (infrared thermography) and thermal
        perceptions will be assessed every 10 minutes prior to the progressive cold-water challenge.
        After 30 minutes of seated rest, pre-immersion measurements of heart rate, blood pressure,
        core temperature, shivering, and thermal perceptions will be conducted and an infrared
        thermography image will be taken. Then, the water immersion tank will be filled up to the
        participant's neck with 35 degrees C (95 degrees F) water. Heart rate, blood pressure, core
        temperature, and shivering indices will be continuously measured. Infrared thermography and
        thermal perceptions will be obtained every 5 minutes throughout the progressive cold-water
        challenge. The temperature of the water will be progressively lowered by ~12 degrees C every
        60 minutes until the water temperature reaches 10 degrees C (50 degrees F) or until the
        participant can no longer tolerate the cold or if rectal temperature reaches 35.5 degrees C
        (95.9 degrees F). Upon completion of the progressive cold water challenge, the water in the
        tank will be rapidly emptied. Participants will gently towel dry and will be able to don a
        circulating warm water perfused suit and/or use a mylar blanket to reestablish core
        temperature.
  
        Participants will be asked to return to the laboratory after 10-14 days to repeat the
        experiment with the drug assignment not yet received. Each participant's order of assignment
        to placebo or drug ingestion (prior to the cold water challenge) over the 2 study visits will
        be randomly assigned.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: Cold temperature deflection point
  time frame: Through session completion, up to 4 hours
  description: Core temperature will be continuously measured using rectal thermistors. The point at which core temperature begins to fall (i.e., deflection point) will be identified using Prism 8 software by plotting core temperature vs. water temperature.
  measure: Thermogenesis - Oxygen Consumption
  time frame: Through session completion, up to 4 hours
  description: Oxygen consumption is one measure of shivering. A pneumotach connected to a mouthpiece or facemask will be used to measure the flow of inspired and expired air. Expired gases will be sampled using oxygen and carbon dioxide sensors to determine oxygen consumption and carbon dioxide production.
  measure: Shivering inflection point - Surface Mechanomyography
  time frame: Through session completion, up to 4 hours
  description: Surface Mechanomyography is one measure of shivering. Three triaxial accelerometers adhered to the skin using adhesive tape on the chest, upper back, and thigh will be used to assess shivering.
  measure: Shivering Inflection point - Bedside Shivering Scale
  time frame: Through session completion, up to 4 hours
  description: The Bedside Shivering Scale is one measure of shivering. Two investigators will subjectively assess shivering by the participants using a Likert scale (0 = none, 3 = Severe) and the scores will be averaged.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Given once, followed by observation for up to 4 hours in a progressively cold water challenge
  arm group label: 100 mg Mirabegron
  arm group type: Experimental
  description: Given once, followed by observation for up to 4 hours in a progressively cold water challenge
  intervention type: Drug
  intervention name: Mirabegron
  description: Dose-response effect on thermogenesis
  arm group label: 100 mg Mirabegron
  other name: Myrbetriq
  intervention type: Drug
  intervention name: Placebo
  description: Placebo control condition
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Blair D Johnson, PhD
  role: Principal Investigator
  affiliation: Indiana University
  last name: Blair D Johnson, PhD
  phone: 8128558699
  email: bj33@indiana.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Indiana University
  investigator full name: Blair D. Johnson, PhD
  investigator title: Associate Professor School of Public Health
  mesh term: Mirabegron
  sharing ipd: No