<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/NCT03269747</url>
  </required_header>
  <id_info>
    <org_study_id>EKNZ 2016-01859</org_study_id>
    <nct_id>NCT03269747</nct_id>
  </id_info>
  <brief_title>Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans</brief_title>
  <acronym>GlucoBAT</acronym>
  <official_title>Short Term Effect of Glucocorticoids on Brown Adipose Tissue Thermogenesis in Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Interventional, Placebo controlled cross-over study to investigate the short-term effects of&#xD;
      glucocorticoids (prednisone) on human brown adipose tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Active brown adipose tissue (BAT) has recently been unambiguously discovered in human adults.&#xD;
      Active BAT increases energy expenditure and improves glucose tolerance. Pharmacological use&#xD;
      of glucocorticoids (GCs) is widespread in clinical practice due to their high&#xD;
      anti-inflammatory efficacy. While short-term administration even of high doses usually is&#xD;
      well tolerated, long-term use of medium to high amounts of GCs leads to unfavorable metabolic&#xD;
      changes, characterized by an increase in intra-abdominal fat mass, a decrease in muscle mass&#xD;
      and insulin resistance.&#xD;
&#xD;
      In line with these well-known side-effects of GCs, several in vitro studies and animal models&#xD;
      demonstrate an inhibiting effect of GCs on BAT thermogenesis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2017</start_date>
  <completion_date type="Actual">April 16, 2019</completion_date>
  <primary_completion_date type="Actual">April 16, 2019</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cold induced thermogenesis</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
    <description>: Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus determined by indirect calorimetry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>fat fraction of supraclavicular BAT</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
    <description>determined by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>volume of supraclavicular BAT</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
    <description>determined by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cold stimulated FGD uptake in brown adipose tissue</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
    <description>determined as SUVmean by FDG-PET/CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SUVmax in the supraclavicular adipose tissue depot</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
    <description>determined by FDG-PET/CT</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Glucose level before and after mild cold stimulus</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>FGF21 level before and after mild cold stimulus</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Expression levels of genes involved in thermogenesis and white to brown adipose tissue transdifferentiation in supraclavicular adipose tissue.</measure>
    <time_frame>at the end of each treatment period (day 7). Prednisone vs. Placebo</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Brown Adipose Tissue</condition>
  <arm_group>
    <arm_group_label>Prednisone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prednisone 40 mg daily for 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo daily for 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>2 tablets of Prednisone 20 Mg in the morning</description>
    <arm_group_label>Prednisone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 Placebo tablets in the morning</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male volunteers&#xD;
&#xD;
          -  BMI between 19-27 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cold induced thermogenesis of less than 5% basal metabolic rate (determined during&#xD;
             screening visit)&#xD;
&#xD;
          -  Contraindications to the class of drugs under study, e.g. known hypersensitivity or&#xD;
             allergy to class of drugs or the investigational product,&#xD;
&#xD;
          -  History of depressive disorder, anxiety disorder&#xD;
&#xD;
          -  History of tuberculosis or latent infection&#xD;
&#xD;
          -  Increased intraocular pressure&#xD;
&#xD;
          -  History of peptic / gastrointestinal ulcer disease&#xD;
&#xD;
          -  Concomitant medication: Non-steroidal anti-inflammatory drugs (NSAID), other&#xD;
             glucocorticoids, diuretics, antihypertensives, fibrates or statins, metformin&#xD;
&#xD;
          -  Other clinically significant concomitant disease states (e.g., renal failure, hepatic&#xD;
             dysfunction, cardiovascular disease, diabetes mellitus),&#xD;
&#xD;
          -  Hypersensitivity to cold (e.g. Raynaud Syndrome)&#xD;
&#xD;
          -  Allergy to local anesthetic&#xD;
&#xD;
          -  Known or suspected non-compliance, drug or alcohol abuse,&#xD;
&#xD;
          -  Inability to follow the procedures of the study&#xD;
&#xD;
          -  Participation in another study with investigational drug within the 30 days preceding&#xD;
             and during the present study,&#xD;
&#xD;
          -  Previous enrolment into the current study,&#xD;
&#xD;
          -  Enrolment of the investigator, his/her family members, employees and other dependent&#xD;
             persons,&#xD;
&#xD;
          -  Hypothyroidism without sufficient substitution&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  MRI incompatible implants&#xD;
&#xD;
          -  Enrolment into another study using ionizing radiation within the previous 12 months.&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Matthias J Betz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Basel, Department of Endocrinology</name>
      <address>
        <city>Basel</city>
        <state>BS</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>June 4, 2019</last_update_submitted>
  <last_update_submitted_qc>June 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>glucocorticoids</keyword>
  <keyword>brown adipose tissue</keyword>
  <keyword>cold induced thermogenesis</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03269747
org study id: EKNZ 2016-01859
nct id: NCT03269747
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Interventional, Placebo controlled cross-over study to investigate the short-term effects of
      glucocorticoids (prednisone) on human brown adipose tissue.
Active brown adipose tissue (BAT) has recently been unambiguously discovered in human adults.
      Active BAT increases energy expenditure and improves glucose tolerance. Pharmacological use
      of glucocorticoids (GCs) is widespread in clinical practice due to their high
      anti-inflammatory efficacy. While short-term administration even of high doses usually is
      well tolerated, long-term use of medium to high amounts of GCs leads to unfavorable metabolic
      changes, characterized by an increase in intra-abdominal fat mass, a decrease in muscle mass
      and insulin resistance.

      In line with these well-known side-effects of GCs, several in vitro studies and animal models
      demonstrate an inhibiting effect of GCs on BAT thermogenesis.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cold induced thermogenesis
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
description: : Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus determined by indirect calorimetry
measure: fat fraction of supraclavicular BAT
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
description: determined by MRI
measure: volume of supraclavicular BAT
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
description: determined by MRI
measure: cold stimulated FGD uptake in brown adipose tissue
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
description: determined as SUVmean by FDG-PET/CT
measure: SUVmax in the supraclavicular adipose tissue depot
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
description: determined by FDG-PET/CT
measure: Glucose level before and after mild cold stimulus
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: FGF21 level before and after mild cold stimulus
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
measure: Expression levels of genes involved in thermogenesis and white to brown adipose tissue transdifferentiation in supraclavicular adipose tissue.
time frame: at the end of each treatment period (day 7). Prednisone vs. Placebo
arm group label: Prednisone
arm group type: Active Comparator
description: Prednisone 40 mg daily for 7 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo daily for 7 days
intervention type: Drug
intervention name: Prednisone
description: 2 tablets of Prednisone 20 Mg in the morning
arm group label: Prednisone
intervention type: Drug
intervention name: Placebo
description: 2 Placebo tablets in the morning
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Matthias J Betz, MD
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Prednisone