<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/NCT03246451</url>
  </required_header>
  <id_info>
    <org_study_id>UHG-CFD-METEX</org_study_id>
    <nct_id>NCT03246451</nct_id>
  </id_info>
  <brief_title>The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin in Patients With T2D</brief_title>
  <official_title>The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin During Meal Ingestion in Patients With T2D</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Gentofte, Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Gentofte, Copenhagen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Delineation of the role of glucagon-like peptide-1 receptor signalling in the&#xD;
      glucose-lowering effect of metformin during meal ingestion in patients with type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim: To evaluate the contribution of metformin-induced GLP-1 secretion on the&#xD;
      glucose-lowering effect of metformin in patients with type 2 diabetes treated with metformin&#xD;
      for 14 days. Furthermore, the investigators aim to elucidate the mechanisms by which&#xD;
      metformin-induced GLP-1 secretion may affect glucose levels in patients with type 2 diabetes.&#xD;
&#xD;
      Fifteen patients with type 2 diabetes treated with lifestyle intervention and/or metformin as&#xD;
      the only glucose-lowering drug will be enrolled in the study. The effect of a 14-day&#xD;
      metformin treatment course on postprandial glucose tolerance will be examined with and&#xD;
      without infusion of the GLP-1 receptor antagonist exendin9-39 in 15 patients with type 2&#xD;
      diabetes.&#xD;
&#xD;
      The double-blinded, placebo-controlled, randomised, cross-over study consists of four study&#xD;
      days with concomitant infusions of A) placebo + placebo, B) placebo + exendin9-39, C)&#xD;
      metformin + placebo and D) metformin + exendin9-39.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">December 10, 2017</completion_date>
  <primary_completion_date type="Actual">December 10, 2017</primary_completion_date>
  <phase>N/A</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma glucose</measure>
    <time_frame>Minutes 240</time_frame>
    <description>The difference between the effect of metformin on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin 9-39.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Glucose Metabolism Disorders</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, oral tablet in 14 days and in liquid meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Saline infusion (9mg/mL) on experimental days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exendin(9-39)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>2-4 tablets in 14 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>1000-2000 mg in 14 days</description>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>9 mg/ml saline infusion during experimental days</description>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exendin (9-39)</intervention_name>
    <description>Infusion of GLP-1 receptor antagonist used as a tool during experimental days</description>
    <arm_group_label>Exendin(9-39)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes for at least three months (diagnosed according to the criteria of the&#xD;
             World Health Organization (WHO)), with a HbA1c &lt;58 mmol/mol.&#xD;
&#xD;
          -  Caucasian ethnicity&#xD;
&#xD;
          -  Lifestyle intervention and/or metformin monotherapy&#xD;
&#xD;
          -  Normal haemoglobin&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  BMI &gt;23 kg/m2 and &lt;35 kg/m2&#xD;
&#xD;
          -  Informed and written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Liver disease&#xD;
&#xD;
          -  Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major&#xD;
             intra-abdominal surgery&#xD;
&#xD;
          -  Hypo- or hyperphosphataemia&#xD;
&#xD;
          -  Reduced kidney function or nephropathy&#xD;
&#xD;
          -  Treatment with medicine that cannot be paused for 12 hours&#xD;
&#xD;
          -  Intake of antibiotics two months prior to study&#xD;
&#xD;
          -  Hypo- or hypercalcaemia&#xD;
&#xD;
          -  Hypo- and hyperthyroidism&#xD;
&#xD;
          -  Treatment with oral anticoagulants&#xD;
&#xD;
          -  Active or recent malignant disease&#xD;
&#xD;
          -  Any treatment or condition requiring acute or sub-acute medical or surgical&#xD;
             intervention&#xD;
&#xD;
          -  Lack of effective birth control in premenopausal women&#xD;
&#xD;
          -  Positive pregnancy test on study days in premenopausal women&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Women who are breastfeeding&#xD;
&#xD;
          -  Any condition considered incompatible with participation by the investigators&#xD;
&#xD;
          -  If the subjects receive any antibiotic treatment while included in the study they will&#xD;
             be excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Filip K Knop, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>UHGentofte, Center for Diabetes Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Diabetes Research</name>
      <address>
        <city>Gentofte</city>
        <state>Copenhagen</state>
        <zip>2900</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>July 6, 2018</last_update_submitted>
  <last_update_submitted_qc>July 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Gentofte, Copenhagen</investigator_affiliation>
    <investigator_full_name>Laura Smidt Hansen</investigator_full_name>
    <investigator_title>Bachelor of Science</investigator_title>
  </responsible_party>
  <keyword>GLP-1</keyword>
  <keyword>glucagon-like peptide-1</keyword>
  <keyword>Metformin</keyword>
  <keyword>Exendin(9-39)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03246451
org study id: UHG-CFD-METEX
nct id: NCT03246451
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Delineation of the role of glucagon-like peptide-1 receptor signalling in the
      glucose-lowering effect of metformin during meal ingestion in patients with type 2 diabetes.
Aim: To evaluate the contribution of metformin-induced GLP-1 secretion on the
      glucose-lowering effect of metformin in patients with type 2 diabetes treated with metformin
      for 14 days. Furthermore, the investigators aim to elucidate the mechanisms by which
      metformin-induced GLP-1 secretion may affect glucose levels in patients with type 2 diabetes.

      Fifteen patients with type 2 diabetes treated with lifestyle intervention and/or metformin as
      the only glucose-lowering drug will be enrolled in the study. The effect of a 14-day
      metformin treatment course on postprandial glucose tolerance will be examined with and
      without infusion of the GLP-1 receptor antagonist exendin9-39 in 15 patients with type 2
      diabetes.

      The double-blinded, placebo-controlled, randomised, cross-over study consists of four study
      days with concomitant infusions of A) placebo + placebo, B) placebo + exendin9-39, C)
      metformin + placebo and D) metformin + exendin9-39.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Plasma glucose
time frame: Minutes 240
description: The difference between the effect of metformin on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin 9-39.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, oral tablet in 14 days and in liquid meal.
arm group label: Metformin
arm group type: Experimental
description: Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.
arm group label: Saline
arm group type: Experimental
description: Saline infusion (9mg/mL) on experimental days
arm group label: Exendin(9-39)
arm group type: Experimental
description: Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 2-4 tablets in 14 days
arm group label: Placebo
intervention type: Drug
intervention name: Metformin
description: 1000-2000 mg in 14 days
arm group label: Metformin
intervention type: Drug
intervention name: Saline
description: 9 mg/ml saline infusion during experimental days
arm group label: Saline
intervention type: Drug
intervention name: Exendin (9-39)
description: Infusion of GLP-1 receptor antagonist used as a tool during experimental days
arm group label: Exendin(9-39)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Filip K Knop, MD, PhD
role: Study Director
affiliation: UHGentofte, Center for Diabetes Research
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Gentofte, Copenhagen
investigator full name: Laura Smidt Hansen
investigator title: Bachelor of Science
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders
mesh term: Metformin
sharing ipd: No