<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/NCT01695109</url>
  </required_header>
  <id_info>
    <org_study_id>702/2008</org_study_id>
    <nct_id>NCT01695109</nct_id>
  </id_info>
  <brief_title>The Influence of Liraglutide on the Reward Properties of Food: an fMRI Study on Healthy Volunteers</brief_title>
  <official_title>The Influence of Liraglutide on the Reward Properties of Food: an fMRI Study on Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinical experience has confirmed the anorexic effect of Glucagon-like-peptide 1 (GLP-1)&#xD;
      mimetics in comparison to DPP-4 inhibitors. A possible mechanism of this effect might be&#xD;
      associated with changes in food choices, as suggested by animal studies. It has been shown&#xD;
      that functional magnetic resonance imaging (fMRI) of the brain is a valuable tool in obesity&#xD;
      research and can be used to study the response of several brain regions to the visual&#xD;
      presentation of preferred in comparison to non preferred food items and to non food items The&#xD;
      aim of this study is to search for possible effects of liraglutide in comparison to placebo&#xD;
      on 1. food choices and 2. changes in brain function as evidenced by fMRI in healthy&#xD;
      volunteers.&#xD;
&#xD;
      Findings of this study will help not only to get deeper insight into the mechanism of the&#xD;
      anorexic effect of GLP-1 mimetics, but also into the regulation of food choices per se. In&#xD;
      the future, it is planned to extend the results of this study in normal weight volunteers to&#xD;
      obese diabetic subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design: The study is designed as a double blind, placebo controlled, randomized crossover&#xD;
      intervention study with two arms (liraglutide first followed by placebo vs. placebo first&#xD;
      followed by liraglutide) in 16 healthy male volunteers. fMRI results and food intake are&#xD;
      compared between groups baseline vs. end of treatment period and placebo vs. liraglutide.&#xD;
&#xD;
      Intervention: A standard dose of 0.6 mg Liraglutide (oder placebo) will be used, and will be&#xD;
      applied subcutaneously each morning for three subsequent days by the study personnel. Study&#xD;
      sessions will be performed on the fourth day after placebo/liraglutide interventions.&#xD;
&#xD;
      Study sessions: On study days participants arrive at the trial centre at 8.00 am after a 12h&#xD;
      fast. Participants are instructed to eat a light dinner around 8.00 pm the previous day and&#xD;
      to spend around 8h resting during the night before the study days. Upon arrival, blood&#xD;
      pressure and heart rate is measured and an iv line is started, from which a blood sample is&#xD;
      taken from the antecubital vein for blood glucose, insulin and plasma hormone concentrations&#xD;
      determination. The occurrence of nausea, vomiting, dizziness or any other adverse events&#xD;
      (AE's) is reviewed together with the subject.&#xD;
&#xD;
      Instructions for the fMRI examination are reviewed together with the subject. The subject is&#xD;
      advised to leave all ferromagnetic items behind, and baseline hunger/satiety visual analogue&#xD;
      scales (VAS) are recorded. Then, the fMRI session with the food items paradigm (together with&#xD;
      repeated recordings of hunger/satiety VAS) takes place. Afterwards, another blood sample and&#xD;
      hunger/satiety VAS is taken and the subject is allowed to eat ad libitum from a buffet&#xD;
      breakfast. Food intake is recorded in detail, including meal choices and calorie intake.&#xD;
      After a final hunger/satiety VAS recording and another blood sample subjects are dismissed&#xD;
      from the trial centre.&#xD;
&#xD;
      Outcome variables: Main outcome variables are fMRI activity in the brain during the high&#xD;
      calorie/low calorie food items paradigm and food intake at the buffet liraglutide vs. placebo&#xD;
      at the end of treatment. Secondary outcome parameters are hunger/satiety VAS ratings, total&#xD;
      and active plasma ghrelin, peptide YY (PYY), glucose and insulin concentrations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">February 2012</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Food intake at an ad libitum buffet</measure>
    <time_frame>day 4</time_frame>
    <description>Food intake at the ad libitum buffet under liraglutide vs. placebo will be measured in details: total amount of calories, and where these calories derive from</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fMRI activity in the brain</measure>
    <time_frame>day 4</time_frame>
    <description>fMRI activity in the brain during the high calorie/low calorie food items paradigm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in hunger and satiety scores on the visual analogue scales (VAS) over time as compared to baseline (measured in mm) during the study session</measure>
    <time_frame>timepoints -10, 90, 130 minutes</time_frame>
    <description>Hunger-VAS forms include the question: How hungry do you feel? Subjects are required to mark their feeling of hunger in a scale of 0 to 100 mm.&#xD;
Satiety-VAS forms include the question: How satt do you feel? Subjects are required to mark their feeling of satiety in a scale of 0 to 100 mm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Ghrelin, PYY, glucose and insulin concentrations during the study session</measure>
    <time_frame>timepoints -10, 90, 130 minutes</time_frame>
    <description>Blood samples will be withdrawn from an intravenous cannula placed circa 10 minutes before the start of the study in the left antecubital vein. Samples will be immediately cooled on ice, centrifuged at 3000 rpm for 10 minutes and then stored at -20°C for the later measurement of insulin, ghrelin and PYY. All assays will be performed using commercial assay kits at the very end of the study with samples belonging to (both study days) one subject being measured within one kit.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Healthy Human Male Subjects</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Liraglutide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liraglutide</intervention_name>
    <description>sc injections of 0.6 mg Liraglutide daily for three continuous days.</description>
    <arm_group_label>Liraglutide</arm_group_label>
    <other_name>Victoza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% NaCl, 0.2 ml</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Isotonic saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male healthy volunteers&#xD;
&#xD;
          -  Age 20-40&#xD;
&#xD;
          -  Non-smokers&#xD;
&#xD;
          -  Normal body weight (body mass index 19 -25 kg/m2)&#xD;
&#xD;
          -  Right handed&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Willingness and ability to comply with the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any history of or current drug abuse including alcohol consumption on a regular basis&#xD;
             or binge drinking&#xD;
&#xD;
          -  Any history of or current psychiatric disease, including any eating disorder, as&#xD;
             assessed by structured interview&#xD;
&#xD;
          -  Any history of dieting&#xD;
&#xD;
          -  Any condition interfering with fMRI measurements such as ferromagnetic implants or&#xD;
             claustrophobia&#xD;
&#xD;
          -  Any evidence of relevant renal, liver, thyroid, cardiovascular, or respiratory illness&#xD;
             at screening examination&#xD;
&#xD;
          -  Any acute illness necessitating medical treatment during the last 3 weeks before study&#xD;
             entry, any permanent intake of medication&#xD;
&#xD;
          -  Any study participation in the last 3 months&#xD;
&#xD;
          -  HIV, hepatitis B or C positive&#xD;
&#xD;
          -  Any disease considered relevant for proper performance of the study or risks to the&#xD;
             participant, at the discretion of the investigator&#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>Anton Luger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Endocrinology and Metabolism, Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <last_update_submitted>September 26, 2012</last_update_submitted>
  <last_update_submitted_qc>September 26, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 27, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Anton Luger</investigator_full_name>
    <investigator_title>Head of the Department of Endocrinology &amp; Metabolism</investigator_title>
  </responsible_party>
  <keyword>GLP1</keyword>
  <keyword>obesity</keyword>
  <keyword>fMRI</keyword>
  <keyword>ghrelin</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liraglutide</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/NCT01695109
org study id: 702/2008
nct id: NCT01695109
lead sponsor: 
has dmc: No
Clinical experience has confirmed the anorexic effect of Glucagon-like-peptide 1 (GLP-1)
      mimetics in comparison to DPP-4 inhibitors. A possible mechanism of this effect might be
      associated with changes in food choices, as suggested by animal studies. It has been shown
      that functional magnetic resonance imaging (fMRI) of the brain is a valuable tool in obesity
      research and can be used to study the response of several brain regions to the visual
      presentation of preferred in comparison to non preferred food items and to non food items The
      aim of this study is to search for possible effects of liraglutide in comparison to placebo
      on 1. food choices and 2. changes in brain function as evidenced by fMRI in healthy
      volunteers.

      Findings of this study will help not only to get deeper insight into the mechanism of the
      anorexic effect of GLP-1 mimetics, but also into the regulation of food choices per se. In
      the future, it is planned to extend the results of this study in normal weight volunteers to
      obese diabetic subjects.
Design: The study is designed as a double blind, placebo controlled, randomized crossover
      intervention study with two arms (liraglutide first followed by placebo vs. placebo first
      followed by liraglutide) in 16 healthy male volunteers. fMRI results and food intake are
      compared between groups baseline vs. end of treatment period and placebo vs. liraglutide.

      Intervention: A standard dose of 0.6 mg Liraglutide (oder placebo) will be used, and will be
      applied subcutaneously each morning for three subsequent days by the study personnel. Study
      sessions will be performed on the fourth day after placebo/liraglutide interventions.

      Study sessions: On study days participants arrive at the trial centre at 8.00 am after a 12h
      fast. Participants are instructed to eat a light dinner around 8.00 pm the previous day and
      to spend around 8h resting during the night before the study days. Upon arrival, blood
      pressure and heart rate is measured and an iv line is started, from which a blood sample is
      taken from the antecubital vein for blood glucose, insulin and plasma hormone concentrations
      determination. The occurrence of nausea, vomiting, dizziness or any other adverse events
      (AE's) is reviewed together with the subject.

      Instructions for the fMRI examination are reviewed together with the subject. The subject is
      advised to leave all ferromagnetic items behind, and baseline hunger/satiety visual analogue
      scales (VAS) are recorded. Then, the fMRI session with the food items paradigm (together with
      repeated recordings of hunger/satiety VAS) takes place. Afterwards, another blood sample and
      hunger/satiety VAS is taken and the subject is allowed to eat ad libitum from a buffet
      breakfast. Food intake is recorded in detail, including meal choices and calorie intake.
      After a final hunger/satiety VAS recording and another blood sample subjects are dismissed
      from the trial centre.

      Outcome variables: Main outcome variables are fMRI activity in the brain during the high
      calorie/low calorie food items paradigm and food intake at the buffet liraglutide vs. placebo
      at the end of treatment. Secondary outcome parameters are hunger/satiety VAS ratings, total
      and active plasma ghrelin, peptide YY (PYY), glucose and insulin concentrations.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Food intake at an ad libitum buffet
time frame: day 4
description: Food intake at the ad libitum buffet under liraglutide vs. placebo will be measured in details: total amount of calories, and where these calories derive from
measure: fMRI activity in the brain
time frame: day 4
description: fMRI activity in the brain during the high calorie/low calorie food items paradigm
measure: Changes in hunger and satiety scores on the visual analogue scales (VAS) over time as compared to baseline (measured in mm) during the study session
time frame: timepoints -10, 90, 130 minutes
description: Hunger-VAS forms include the question: How hungry do you feel? Subjects are required to mark their feeling of hunger in a scale of 0 to 100 mm.
Satiety-VAS forms include the question: How satt do you feel? Subjects are required to mark their feeling of satiety in a scale of 0 to 100 mm.
measure: Changes in Ghrelin, PYY, glucose and insulin concentrations during the study session
time frame: timepoints -10, 90, 130 minutes
description: Blood samples will be withdrawn from an intravenous cannula placed circa 10 minutes before the start of the study in the left antecubital vein. Samples will be immediately cooled on ice, centrifuged at 3000 rpm for 10 minutes and then stored at -20°C for the later measurement of insulin, ghrelin and PYY. All assays will be performed using commercial assay kits at the very end of the study with samples belonging to (both study days) one subject being measured within one kit.
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: Liraglutide
arm group type: Active Comparator
intervention type: Drug
intervention name: Liraglutide
description: sc injections of 0.6 mg Liraglutide daily for three continuous days.
arm group label: Liraglutide
other name: Victoza
intervention type: Drug
intervention name: Placebo
description: 0.9% NaCl, 0.2 ml
arm group label: Placebo
other name: Isotonic saline
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anton Luger, MD
role: Principal Investigator
affiliation: Medical University of Vienna
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Anton Luger
investigator title: Head of the Department of Endocrinology & Metabolism
mesh term: Liraglutide