<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/NCT03002675</url>
  </required_header>
  <id_info>
    <org_study_id>P16.078</org_study_id>
    <nct_id>NCT03002675</nct_id>
  </id_info>
  <brief_title>Exenatide and Brown Adipose Tissue</brief_title>
  <acronym>exe01</acronym>
  <official_title>The Effect of Exenatide on Brown Adipose Tissue Activity and Energy Expenditure in Healthy Young Men</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ingrid Jazet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Leiden University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The obesity epidemic has led to a enormous increase in the prevalence of type 2 diabetes&#xD;
      mellitus (T2D), dyslipidemia and cardiovascular events. Particularly South Asians, who&#xD;
      comprise 1/5 of the world population, are at increased risk of developing a disadvantageous&#xD;
      metabolic phenotype and these diseases. Moreover, T2D occurs at a younger age and at a lower&#xD;
      BMI when compared to white Caucasians. Recent research has shown that South Asians not only&#xD;
      have a lower energy expenditure than their Caucasian counterparts, but also less active brown&#xD;
      adipose tissue (BAT).&#xD;
&#xD;
      For some time, it has been known that adult humans have active BAT. This metabolic tissue&#xD;
      produces heat by combusting triglycerides, in contrast to white adipose tissue, which stores&#xD;
      this form of energy. It has been shown that activation of BAT has a positive effect on whole&#xD;
      body metabolism, via increasing energy expenditure and improving glucose- and lipid&#xD;
      metabolism. For this matter, BAT has been proposed as a major key player in energy&#xD;
      homeostasis, which may be implemented in the current combat against the obesity epidemic.&#xD;
      Aside from cold exposure, more research focuses on pharmacological activation of BAT.&#xD;
&#xD;
      Glucagon-like peptide 1 (GLP-1) is an incretin hormone which is produced by intestinal&#xD;
      L-cells and upon food intake stimulates insulin secretion by pancreatic beta cells. The GLP-1&#xD;
      analogue Exenatide is a currently much used antidiabetic drug to reduce hyperglycemia via&#xD;
      this aforementioned mechanism. Beyond its blood glucose-improving effects, Exenatide has also&#xD;
      shown to lower body weight and improve dyslipidemia in T2D patients. Elucidation of the&#xD;
      underlying mechanism of these beneficial effects is highly relevant.&#xD;
&#xD;
      Recent preclinical research in our group has shown that central activation of the GLP-1&#xD;
      receptor through exenatide increases BAT activity and thereby contributes to weight loss and&#xD;
      improvement of dyslipidemia. The aim of this research project is to investigate whether&#xD;
      exenatide is also able to activate BAT and increase resting energy expenditure, thereby&#xD;
      improving glucose- and lipid metabolism and reducing fat mass and body weight in humans.&#xD;
      Moreover, the investigators aim to validate the MRI scan as a novel way to measure BAT&#xD;
      activity. The investigators hope that these forthcoming findings lead to the discovery of new&#xD;
      treatment strategies against obesity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current study is an open-label single arm prospective design, including 24 healthy young&#xD;
      lean males (BMI between 18 and 25 kg/m2), of whom 12 Dutch South Asians and 12 Dutch&#xD;
      Caucasians. After a medical screening, included subjects will receive 12 weeks of treatment&#xD;
      with the GLP-1 analogue exenatide (Bydureon; 2 mg s.c. 1x/wk). Study subjects will visit the&#xD;
      LUMC weekly. Before and after treatment there will be a study day, in which BAT (by means of&#xD;
      18F-FDG PET-CT scan and MRI scan), resting energy expenditure (measured by indirect&#xD;
      calorimetry) and fat mass (by bio-impedance analysis) will be measured. Moreover, blood will&#xD;
      be drawn to investigate the effects of exenatide on lipid- and glucose metabolism.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2016</start_date>
  <primary_completion_date type="Anticipated">June 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The effect of exenatide on BAT activity and energy expenditure in healthy young South Asian compared to white Caucasian men</measure>
    <time_frame>End of the study, up to 21 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visualisation of BAT as measured with MRI scan compared to FDG-PET CT</measure>
    <time_frame>End of the study, up to 21 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>exenatide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive exenatide (Bydureon, 2mg s.c. 1x/wk, AstraZeneca) during 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bydureon</intervention_name>
    <description>exenatide (Bydureon) 2mg s.c. 1x/wk</description>
    <arm_group_label>exenatide</arm_group_label>
    <other_name>exenatide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Dutch South Asian or white Caucasian male, 20-30 years&#xD;
&#xD;
          -  BMI ≥ 18 and ≤ 25 kg/m2&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 25 kg/m2 or &lt; 18 kg/m2&#xD;
&#xD;
          -  Use of medication known to influence glucose and/or lipid metabolism or brown fat&#xD;
             activity (e.g. beta blockers)&#xD;
&#xD;
          -  Any significant chronic disease&#xD;
&#xD;
          -  Renal, hepatic or endocrine disease&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Participation in an intensive weight-loss program or vigorous exercise program during&#xD;
             the last year before the start of the study&#xD;
&#xD;
          -  Recent participation in other research projects (within the last 3 months),&#xD;
             participation in 2 or more projects in one year&#xD;
&#xD;
          -  Contraindications for undergoing an MRI scan:&#xD;
&#xD;
          -  Presence of non-MR safe metal implants or objects in the body.&#xD;
&#xD;
          -  Pacemaker, neurostimulator, hydrocephalus pump, drug pump, non-removable hearing aid,&#xD;
             large recent tattoos.&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Tinnitus or hyperacusis&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ingrid Jazet, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leiden University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ingrid Jazet Jazet, MD</last_name>
    <email>i.m.jazet@lumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <state>Zuid-Holland</state>
        <zip>2333 ZA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ingrid Jazet, MD, PhD</last_name>
      <phone>+33-715268161</phone>
      <email>i.m.jazet@lumc.nl</email>
    </contact>
    <contact_backup>
      <last_name>Mariëtte Boon, PhD</last_name>
      <phone>+31-715265462</phone>
      <email>m.r.boon@lumc.nl</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 26, 2016</study_first_posted>
  <last_update_submitted>December 21, 2016</last_update_submitted>
  <last_update_submitted_qc>December 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 26, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Leiden University Medical Center</investigator_affiliation>
    <investigator_full_name>Ingrid Jazet</investigator_full_name>
    <investigator_title>Dr</investigator_title>
  </responsible_party>
  <keyword>Adipose tissue</keyword>
  <keyword>Type 2 diabetes</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exenatide</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/NCT03002675
org study id: P16.078
nct id: NCT03002675
lead sponsor: 
collaborator: 
has dmc: Yes
The obesity epidemic has led to a enormous increase in the prevalence of type 2 diabetes
      mellitus (T2D), dyslipidemia and cardiovascular events. Particularly South Asians, who
      comprise 1/5 of the world population, are at increased risk of developing a disadvantageous
      metabolic phenotype and these diseases. Moreover, T2D occurs at a younger age and at a lower
      BMI when compared to white Caucasians. Recent research has shown that South Asians not only
      have a lower energy expenditure than their Caucasian counterparts, but also less active brown
      adipose tissue (BAT).

      For some time, it has been known that adult humans have active BAT. This metabolic tissue
      produces heat by combusting triglycerides, in contrast to white adipose tissue, which stores
      this form of energy. It has been shown that activation of BAT has a positive effect on whole
      body metabolism, via increasing energy expenditure and improving glucose- and lipid
      metabolism. For this matter, BAT has been proposed as a major key player in energy
      homeostasis, which may be implemented in the current combat against the obesity epidemic.
      Aside from cold exposure, more research focuses on pharmacological activation of BAT.

      Glucagon-like peptide 1 (GLP-1) is an incretin hormone which is produced by intestinal
      L-cells and upon food intake stimulates insulin secretion by pancreatic beta cells. The GLP-1
      analogue Exenatide is a currently much used antidiabetic drug to reduce hyperglycemia via
      this aforementioned mechanism. Beyond its blood glucose-improving effects, Exenatide has also
      shown to lower body weight and improve dyslipidemia in T2D patients. Elucidation of the
      underlying mechanism of these beneficial effects is highly relevant.

      Recent preclinical research in our group has shown that central activation of the GLP-1
      receptor through exenatide increases BAT activity and thereby contributes to weight loss and
      improvement of dyslipidemia. The aim of this research project is to investigate whether
      exenatide is also able to activate BAT and increase resting energy expenditure, thereby
      improving glucose- and lipid metabolism and reducing fat mass and body weight in humans.
      Moreover, the investigators aim to validate the MRI scan as a novel way to measure BAT
      activity. The investigators hope that these forthcoming findings lead to the discovery of new
      treatment strategies against obesity.
The current study is an open-label single arm prospective design, including 24 healthy young
      lean males (BMI between 18 and 25 kg/m2), of whom 12 Dutch South Asians and 12 Dutch
      Caucasians. After a medical screening, included subjects will receive 12 weeks of treatment
      with the GLP-1 analogue exenatide (Bydureon; 2 mg s.c. 1x/wk). Study subjects will visit the
      LUMC weekly. Before and after treatment there will be a study day, in which BAT (by means of
      18F-FDG PET-CT scan and MRI scan), resting energy expenditure (measured by indirect
      calorimetry) and fat mass (by bio-impedance analysis) will be measured. Moreover, blood will
      be drawn to investigate the effects of exenatide on lipid- and glucose metabolism.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The effect of exenatide on BAT activity and energy expenditure in healthy young South Asian compared to white Caucasian men
time frame: End of the study, up to 21 months
measure: Visualisation of BAT as measured with MRI scan compared to FDG-PET CT
time frame: End of the study, up to 21 months
arm group label: exenatide
arm group type: Experimental
description: Participants will receive exenatide (Bydureon, 2mg s.c. 1x/wk, AstraZeneca) during 12 weeks
intervention type: Drug
intervention name: Bydureon
description: exenatide (Bydureon) 2mg s.c. 1x/wk
arm group label: exenatide
other name: exenatide
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ingrid Jazet, MD
role: Principal Investigator
affiliation: Leiden University Medical Center
last name: Ingrid Jazet Jazet, MD
email: i.m.jazet@lumc.nl
facility: 
status: Recruiting
contact: 
contact backup: 
country: Netherlands
responsible party type: Sponsor-Investigator
investigator affiliation: Leiden University Medical Center
investigator full name: Ingrid Jazet
investigator title: Dr
mesh term: Exenatide