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/NCT06011265</url>
    </required_header>
    <id_info>
      <org_study_id>2981</org_study_id>
      <nct_id>NCT06011265</nct_id>
    </id_info>
    <brief_title>Does Mirabegron Increase the Body Heat Generated by the Nervous System</brief_title>
    <official_title>Does Mirabegron Increase the Body Heat Generated by the Nervous System</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Christopher Bell</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Indiana University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Colorado State 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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Acute mirabegron administration has been shown to increase brown fat activity in humans.&#xD;
        Long-term mirabegron administration upregulates brown fat, and appears to improve glucose&#xD;
        regulation, and change skeletal muscle phenotype.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The Undersea Medicine Program at the Office of Naval Research has invited Indiana University,&#xD;
        Rutgers and Colorado State University, to explore the potential of the medication,&#xD;
        Mirabegron, to improve the cold tolerance of Navy personnel. Indiana University will submit&#xD;
        the formal application for research funding. Research activities at Colorado State University&#xD;
        will be supported by a sub-contact from Indiana University.&#xD;
  &#xD;
        The project will address four hypotheses. One of these hypotheses will be investigated&#xD;
        exclusively at Colorado State University during the second year of the project. The proposed&#xD;
        activities at Colorado State University will be unique; the link to activities performed by&#xD;
        Indiana University and Rutgers is thematic only.&#xD;
  &#xD;
        Specialized Navy personnel are required to undertake duties while immersed in cold water for&#xD;
        prolonged periods. These dives regularly require the use of external thermal protection&#xD;
        (i.e., wet suits and dry suits). However, external thermal protection during prolonged&#xD;
        cold-water diving is often times insufficient to maintain body temperature and thermal&#xD;
        comfort, thereby potentially negatively impacting the safety and success of diving missions.&#xD;
        Accordingly, developing an alternative strategy that can improve tolerance to cold-water&#xD;
        immersion is of important interest to Navy divers and special forces. In this regard, the&#xD;
        pharmaceutical, mirabegron, may hold considerable promise to mitigate the negative effects of&#xD;
        cold-water immersion on cold-water tolerance by increasing thermogenesis (the generation of&#xD;
        heat). Mirabegron (Myrbetriq®, extended-release tablet, Astellas Pharma), is a medication&#xD;
        approved by the Food and Drug Administration for the treatment of overactive bladder. In&#xD;
        2020, it was the 160th most commonly prescribed medication in the United States, with more&#xD;
        than three million prescriptions. The mechanism of action is stimulation of beta-3-adrenergic&#xD;
        receptors (receptors that are usually stimulated by the sympathetic nervous system).&#xD;
        Mirabegron is also known to stimulate brown fat, a metabolically active, heat-generating&#xD;
        tissue. The overall goals of the project are to determine the efficacy of acute mirabegron&#xD;
        administration to improve cold tolerance and determine if mirabegron can accentuate&#xD;
        thermogenesis during sympathetic activation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 27, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <phase>Early Phase 1</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>Crossover with a washout of at least 10 days</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Single (Participant)</masking>
      <masking_description>Single Blind</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in metabolic rate compared to baseline during each stage as measured by indirect calorimetry</measure>
      <time_frame>Immediately after each infusion</time_frame>
      <description>Participants will undergo a 45 minute resting metabolic rate assessment and then consume Mirabegron or Placebo. Afterwards, they will undergo three 30 minute infusions of Isoproterenol consisting of doses of 6, 12, and 24ng/kg FFM</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in temperature among the top 10% of hottest pixels as identified via thermal camera and FLIR research software in the supraclavicular region during each isoproterenol infusion.</measure>
      <time_frame>Immediately after each infusion.</time_frame>
      <description>At the conclusion of each of the 3 isoproterenol infusions, participants will have thermal images taken of their supraclavicular region to identify brown fat activation.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in core temperature measured via oral thermometer during each stage.</measure>
      <time_frame>Immediately after each infusion.</time_frame>
      <description>Core temperature will be measured via oral thermometer at the conclusion of each of the three isoproterenol infusions.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Thermoregulation</condition>
    <arm_group>
      <arm_group_label>Mirabegron + Isoproterenol</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>100mg oral + Isoproterenol IV Infusion; 3 doses, 6, 12, 24ng/ kg Fat Free Mass</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo + Isoproterenol</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Empty Capsule + Isoproterenol IV Infusion; 3 doses, 6, 12, 24ng/ kg Fat Free Mass</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Myrbetriq 25Mg Extended-Release Tablet</intervention_name>
      <description>Participants take 4x 25mg Myrbetriq 25Mg Extended-Release Tablet orally.</description>
      <arm_group_label>Mirabegron + Isoproterenol</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participants take empty capsule orally</description>
      <arm_group_label>Placebo + Isoproterenol</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  age 18-40 years,&#xD;
  &#xD;
            -  regular participation in more than 150 minutes of moderate intensity exercise, every&#xD;
               week, during the previous two years.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of autonomic, cardio-pulmonary, and/or metabolic disease (including heart&#xD;
               failure, hypertension, arrhythmia, vascular disease, and/or diabetes)&#xD;
  &#xD;
            -  contraindication for mirabegron ingestion, such as previously diagnosed liver and/or&#xD;
               kidney dysfunction,&#xD;
  &#xD;
            -  use of medication that may unfavorably interact with mirabegron, including&#xD;
               thioridazine (Mellaril™ and Mellaril-S™), flecainide (Tambocor®), propafenone&#xD;
               (Rythmol®), digoxin (Lanoxin®) and solifenacin succinate (VESIcare®)&#xD;
  &#xD;
            -  pregnancy or breast feeding&#xD;
  &#xD;
            -  habitual use of tobacco/nicotine products (2 or more uses within the previous month)&#xD;
  &#xD;
            -  any type of bladder dysfunction, taking medication related to bladder issues, or a&#xD;
               history of bladder issues.&#xD;
  &#xD;
            -  Sulfite Allergy '&#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>Christopher Bell, Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Colorado State University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Christopher Bell, Ph.D.</last_name>
      <phone>9704917522</phone>
      <email>Christopher.Bell@colostate.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Taylor R Ewell, MS</last_name>
      <phone>7197611417</phone>
      <email>taylor.ewell@colostate.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Colorado State University</name>
        <address>
          <city>Fort Collins</city>
          <state>Colorado</state>
          <zip>80523</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Christopher Bell, Ph.D.</last_name>
        <phone>970-491-7522</phone>
        <email>christopher.bell@colostate.edu</email>
      </contact>
      <contact_backup>
        <last_name>Taylor R Ewell, MS</last_name>
        <phone>7197611417</phone>
        <email>taylor.ewell@colostate.edu</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 25, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Colorado State University</investigator_affiliation>
      <investigator_full_name>Christopher Bell</investigator_full_name>
      <investigator_title>Associate Professor</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/NCT06011265
  org study id: 2981
  nct id: NCT06011265
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  Acute mirabegron administration has been shown to increase brown fat activity in humans.
        Long-term mirabegron administration upregulates brown fat, and appears to improve glucose
        regulation, and change skeletal muscle phenotype.
  The Undersea Medicine Program at the Office of Naval Research has invited Indiana University,
        Rutgers and Colorado State University, to explore the potential of the medication,
        Mirabegron, to improve the cold tolerance of Navy personnel. Indiana University will submit
        the formal application for research funding. Research activities at Colorado State University
        will be supported by a sub-contact from Indiana University.
  
        The project will address four hypotheses. One of these hypotheses will be investigated
        exclusively at Colorado State University during the second year of the project. The proposed
        activities at Colorado State University will be unique; the link to activities performed by
        Indiana University and Rutgers is thematic only.
  
        Specialized Navy personnel are required to undertake duties while immersed in cold water for
        prolonged periods. These dives regularly require the use of external thermal protection
        (i.e., wet suits and dry suits). However, external thermal protection during prolonged
        cold-water diving is often times insufficient to maintain body temperature and thermal
        comfort, thereby potentially negatively impacting the safety and success of diving missions.
        Accordingly, developing an alternative strategy that can improve tolerance to cold-water
        immersion is of important interest to Navy divers and special forces. In this regard, the
        pharmaceutical, mirabegron, may hold considerable promise to mitigate the negative effects of
        cold-water immersion on cold-water tolerance by increasing thermogenesis (the generation of
        heat). Mirabegron (Myrbetriq®, extended-release tablet, Astellas Pharma), is a medication
        approved by the Food and Drug Administration for the treatment of overactive bladder. In
        2020, it was the 160th most commonly prescribed medication in the United States, with more
        than three million prescriptions. The mechanism of action is stimulation of beta-3-adrenergic
        receptors (receptors that are usually stimulated by the sympathetic nervous system).
        Mirabegron is also known to stimulate brown fat, a metabolically active, heat-generating
        tissue. The overall goals of the project are to determine the efficacy of acute mirabegron
        administration to improve cold tolerance and determine if mirabegron can accentuate
        thermogenesis during sympathetic activation.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Crossover with a washout of at least 10 days
  primary purpose: Basic Science
  masking: Single (Participant)
  masking description: Single Blind
  measure: Change in metabolic rate compared to baseline during each stage as measured by indirect calorimetry
  time frame: Immediately after each infusion
  description: Participants will undergo a 45 minute resting metabolic rate assessment and then consume Mirabegron or Placebo. Afterwards, they will undergo three 30 minute infusions of Isoproterenol consisting of doses of 6, 12, and 24ng/kg FFM
  measure: Change in temperature among the top 10% of hottest pixels as identified via thermal camera and FLIR research software in the supraclavicular region during each isoproterenol infusion.
  time frame: Immediately after each infusion.
  description: At the conclusion of each of the 3 isoproterenol infusions, participants will have thermal images taken of their supraclavicular region to identify brown fat activation.
  measure: Change in core temperature measured via oral thermometer during each stage.
  time frame: Immediately after each infusion.
  description: Core temperature will be measured via oral thermometer at the conclusion of each of the three isoproterenol infusions.
  arm group label: Mirabegron + Isoproterenol
  arm group type: Experimental
  description: 100mg oral + Isoproterenol IV Infusion; 3 doses, 6, 12, 24ng/ kg Fat Free Mass
  arm group label: Placebo + Isoproterenol
  arm group type: Placebo Comparator
  description: Empty Capsule + Isoproterenol IV Infusion; 3 doses, 6, 12, 24ng/ kg Fat Free Mass
  intervention type: Drug
  intervention name: Myrbetriq 25Mg Extended-Release Tablet
  description: Participants take 4x 25mg Myrbetriq 25Mg Extended-Release Tablet orally.
  arm group label: Mirabegron + Isoproterenol
  intervention type: Drug
  intervention name: Placebo
  description: Participants take empty capsule orally
  arm group label: Placebo + Isoproterenol
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Christopher Bell, Ph.D.
  role: Principal Investigator
  affiliation: Colorado State University
  last name: Christopher Bell, Ph.D.
  phone: 9704917522
  email: Christopher.Bell@colostate.edu
  last name: Taylor R Ewell, MS
  phone: 7197611417
  email: taylor.ewell@colostate.edu
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: Colorado State University
  investigator full name: Christopher Bell
  investigator title: Associate Professor
  mesh term: Mirabegron
  sharing ipd: No