<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/NCT01674946</url>
  </required_header>
  <id_info>
    <org_study_id>EKBB 140/11</org_study_id>
    <nct_id>NCT01674946</nct_id>
  </id_info>
  <brief_title>Effect of Bile Acids on the Secretion of Satiation Peptides in Humans</brief_title>
  <official_title>Effect of Intraduodenal Perfusion of Bile Acids on the Secretion of Gastrointestinal Satiation Peptides in Healthy Male Volunteers</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is do determine the functional significance of the G&#xD;
      protein-coupled receptor TGR5 in the secretion of GI satiation peptides by using natural bile&#xD;
      acids and oleanolic acid (triterpenoid compound of plant origin) as TGR5 agonists.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TGR5 is expressed in GLP-1-secreting cell lines and L cells from mice; gain- and&#xD;
      loss-of-function models suggest a physiological role for TGR5 activation on GLP-1 secretion&#xD;
      in rodents. TGR5 signaling showed improved postprandial glucose tolerance in obese mice,&#xD;
      associated with marked postprandial GLP-1 release and insulin secretion. In contrast, TGR5-/-&#xD;
      mice exhibited reduced glucose tolerance. In animals, TGR5 activation has been shown for&#xD;
      natural bile acids (BAs) and triterpenoid compounds of plant origin, such as oleanolic acid&#xD;
      (OA), suggesting a role for postprandial BAs in modulating nutrient-induced GLP-1 secretion.&#xD;
      We therefore hypothesized that intraduodenal (ID) perfusions of TGR5 agonists (BAs and OA)&#xD;
      stimulate the secretion of GLP-1 with respective changes in the glucose metabolism of healthy&#xD;
      humans.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2011</start_date>
  <completion_date type="Actual">May 2012</completion_date>
  <primary_completion_date type="Actual">December 2011</primary_completion_date>
  <phase>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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gastrointestinal satiation peptide secretion</measure>
    <time_frame>3 hours blood sampling</time_frame>
    <description>Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum bile acids</measure>
    <time_frame>3 hours blood sampling</time_frame>
    <description>Assessment of serum bile acids levels to BA and OA stimulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite perceptions during 3 hours using visual analogue scales</measure>
    <time_frame>3 hours</time_frame>
    <description>Assessment of the following appetite perceptions markers: feelings of hunger, feelings of prospective food consumption, feelings of fullness and feelings of satiety using validated visual analogue scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose and insulin secretion</measure>
    <time_frame>3 hours blood sampling</time_frame>
    <description>Assessment of plasma glucose and insulin levels to BA and OA stimulation</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Echolocation</condition>
  <arm_group>
    <arm_group_label>ID saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>ID saline by feeding tube</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ID saline + CDCA (5 mmol/L)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CDCA = chenodeoxycholic acid (primary bile acid)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ID + CDCA (15 mmol/L)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>CDCA = chenodeoxycholic acid (primary bile acid)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ID saline + oleanolic acid (1 mmol/L)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ID saline + CDCA (5 mmol/L) + oleic acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ID saline + oleic acid (20 mmol/L)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>saline</intervention_name>
    <description>intraduodenal perfusion</description>
    <arm_group_label>ID + CDCA (15 mmol/L)</arm_group_label>
    <arm_group_label>ID saline</arm_group_label>
    <arm_group_label>ID saline + CDCA (5 mmol/L)</arm_group_label>
    <arm_group_label>ID saline + CDCA (5 mmol/L) + oleic acid</arm_group_label>
    <arm_group_label>ID saline + oleanolic acid (1 mmol/L)</arm_group_label>
    <arm_group_label>ID saline + oleic acid (20 mmol/L)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>bile acid (CDCA, chenodeoxycholic acid)</intervention_name>
    <description>intraduodenal perfusion</description>
    <arm_group_label>ID + CDCA (15 mmol/L)</arm_group_label>
    <arm_group_label>ID saline + CDCA (5 mmol/L)</arm_group_label>
    <arm_group_label>ID saline + CDCA (5 mmol/L) + oleic acid</arm_group_label>
    <other_name>primary bile acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>oleanolic acid</intervention_name>
    <description>intraduodenal perfusion</description>
    <arm_group_label>ID saline + oleanolic acid (1 mmol/L)</arm_group_label>
    <other_name>triterpenoid compound of plant origin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>oleic acid</intervention_name>
    <description>intraduodenal perfusion</description>
    <arm_group_label>ID saline + CDCA (5 mmol/L) + oleic acid</arm_group_label>
    <arm_group_label>ID saline + oleic acid (20 mmol/L)</arm_group_label>
    <other_name>fatty acid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects&#xD;
&#xD;
          -  BMI of 19.0-24.5&#xD;
&#xD;
          -  Age 18-40&#xD;
&#xD;
          -  Stable body weight for at least 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Substance abuse&#xD;
&#xD;
          -  Regular intake of medication&#xD;
&#xD;
          -  Medical of psychiatric illness&#xD;
&#xD;
          -  Gastrointestinal disorders or food allergies&#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>Christoph Beglinger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Basel, Phase 1 Research Unit, Basel Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Basel, Phase 1 Research Unit</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <last_update_submitted>August 24, 2012</last_update_submitted>
  <last_update_submitted_qc>August 24, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 29, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GI-physiology</keyword>
  <keyword>CDCA</keyword>
  <keyword>bile acids</keyword>
  <keyword>TGR5</keyword>
  <keyword>satiation peptides</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chenodeoxycholic Acid</mesh_term>
    <mesh_term>Bile Acids and Salts</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/NCT01674946
org study id: EKBB 140/11
nct id: NCT01674946
lead sponsor: 
has dmc: Yes
The purpose of this study is do determine the functional significance of the G
      protein-coupled receptor TGR5 in the secretion of GI satiation peptides by using natural bile
      acids and oleanolic acid (triterpenoid compound of plant origin) as TGR5 agonists.
TGR5 is expressed in GLP-1-secreting cell lines and L cells from mice; gain- and
      loss-of-function models suggest a physiological role for TGR5 activation on GLP-1 secretion
      in rodents. TGR5 signaling showed improved postprandial glucose tolerance in obese mice,
      associated with marked postprandial GLP-1 release and insulin secretion. In contrast, TGR5-/-
      mice exhibited reduced glucose tolerance. In animals, TGR5 activation has been shown for
      natural bile acids (BAs) and triterpenoid compounds of plant origin, such as oleanolic acid
      (OA), suggesting a role for postprandial BAs in modulating nutrient-induced GLP-1 secretion.
      We therefore hypothesized that intraduodenal (ID) perfusions of TGR5 agonists (BAs and OA)
      stimulate the secretion of GLP-1 with respective changes in the glucose metabolism of healthy
      humans.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Gastrointestinal satiation peptide secretion
time frame: 3 hours blood sampling
description: Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation
measure: Serum bile acids
time frame: 3 hours blood sampling
description: Assessment of serum bile acids levels to BA and OA stimulation
measure: Appetite perceptions during 3 hours using visual analogue scales
time frame: 3 hours
description: Assessment of the following appetite perceptions markers: feelings of hunger, feelings of prospective food consumption, feelings of fullness and feelings of satiety using validated visual analogue scales
measure: Glucose and insulin secretion
time frame: 3 hours blood sampling
description: Assessment of plasma glucose and insulin levels to BA and OA stimulation
arm group label: ID saline
arm group type: Placebo Comparator
description: ID saline by feeding tube
arm group label: ID saline + CDCA (5 mmol/L)
arm group type: Active Comparator
description: CDCA = chenodeoxycholic acid (primary bile acid)
arm group label: ID + CDCA (15 mmol/L)
arm group type: Active Comparator
description: CDCA = chenodeoxycholic acid (primary bile acid)
arm group label: ID saline + oleanolic acid (1 mmol/L)
arm group type: Active Comparator
arm group label: ID saline + CDCA (5 mmol/L) + oleic acid
arm group type: Active Comparator
arm group label: ID saline + oleic acid (20 mmol/L)
arm group type: Placebo Comparator
intervention type: Other
intervention name: saline
description: intraduodenal perfusion
arm group label: ID + CDCA (15 mmol/L)
arm group label: ID saline
arm group label: ID saline + CDCA (5 mmol/L)
arm group label: ID saline + CDCA (5 mmol/L) + oleic acid
arm group label: ID saline + oleanolic acid (1 mmol/L)
arm group label: ID saline + oleic acid (20 mmol/L)
intervention type: Other
intervention name: bile acid (CDCA, chenodeoxycholic acid)
description: intraduodenal perfusion
arm group label: ID + CDCA (15 mmol/L)
arm group label: ID saline + CDCA (5 mmol/L)
arm group label: ID saline + CDCA (5 mmol/L) + oleic acid
other name: primary bile acid
intervention type: Other
intervention name: oleanolic acid
description: intraduodenal perfusion
arm group label: ID saline + oleanolic acid (1 mmol/L)
other name: triterpenoid compound of plant origin
intervention type: Dietary Supplement
intervention name: oleic acid
description: intraduodenal perfusion
arm group label: ID saline + CDCA (5 mmol/L) + oleic acid
arm group label: ID saline + oleic acid (20 mmol/L)
other name: fatty acid
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christoph Beglinger, MD
role: Principal Investigator
affiliation: University Hospital Basel, Phase 1 Research Unit, Basel Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Chenodeoxycholic Acid
mesh term: Bile Acids and Salts