<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/NCT01729156</url>
  </required_header>
  <id_info>
    <org_study_id>C11palmitatMetformin</org_study_id>
    <nct_id>NCT01729156</nct_id>
  </id_info>
  <brief_title>Effects of Metformin on Hepatic FFA Metabolism</brief_title>
  <official_title>Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lars Christian Gormsen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism.&#xD;
      Whereas there is general agreement that the blood glucose lowering effect of metformin&#xD;
      results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug&#xD;
      lowers blood triglyceride concentration. There are indications that it enhances hepatic free&#xD;
      fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as&#xD;
      very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily&#xD;
      accessible for sampling in humans and data on the clinical effects of metformin in the liver&#xD;
      are therefore lacking. This may change due to the increasing use of the positron emission&#xD;
      tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a&#xD;
      fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.&#xD;
&#xD;
      Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic&#xD;
      lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.&#xD;
&#xD;
      Design: Randomized, placebo controlled, double-blind parallel study with patients receiving&#xD;
      either metformin or placebo. A control group of BMI and age-matched non-diabetic individuals&#xD;
      will receive metformin for 3 months.&#xD;
&#xD;
      Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing&#xD;
      hepatic fatty acid oxidation&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 5, 2017</completion_date>
  <primary_completion_date type="Actual">May 5, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hepatic Fatty Acid Oxidation</measure>
    <time_frame>90 days</time_frame>
    <description>Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hepatic Fatty Acid Reesterification</measure>
    <time_frame>90 days</time_frame>
    <description>Hepatic fatty acid reesterification assessed by C11-palmitate PET</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hepatic Fatty Acid Uptake</measure>
    <time_frame>90 days</time_frame>
    <description>Hepatic fatty acid uptake assessed by C11-palmitate PET</description>
  </primary_outcome>
  <primary_outcome>
    <measure>VLDL-TG Secretion</measure>
    <time_frame>90 days</time_frame>
    <description>Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole Body Glucose Rd</measure>
    <time_frame>90 days</time_frame>
    <description>Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fatty Acid Turnover</measure>
    <time_frame>90 days</time_frame>
    <description>Fatty acid turnover assessed as whole body C11-palmitate turnover</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VLDL-TG Oxidation</measure>
    <time_frame>90 days</time_frame>
    <description>VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Dyslipidemia</condition>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Metformin &quot;Sandoz&quot;, 1000 mg twice daily for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>1000 mg metformin twice daily in 3 months</description>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_label>Metformin</arm_group_label>
    <other_name>Metformin &quot;Sandoz&quot; 500 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 tablets twice daily in 3 months</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Recently diagnosed type 2 diabetes&#xD;
&#xD;
          -  Age 50-70 years&#xD;
&#xD;
          -  BMI&lt;40&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Insulin treatment&#xD;
&#xD;
          -  NASH (non alcoholic steatohepatitis)&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Anemia&#xD;
&#xD;
          -  HbA1C&gt;8.5 %&#xD;
&#xD;
          -  Chronic or acute pancreatitis&#xD;
&#xD;
          -  Alcohol or medicine abuse&#xD;
&#xD;
          -  Allergy towards metformin&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Severe obesity (weight &gt;130 kilogram)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars C Gormsen, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aarhus University Hospital</affiliation>
  </overall_official>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>September 24, 2019</results_first_submitted>
  <results_first_submitted_qc>September 24, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 15, 2019</results_first_posted>
  <last_update_submitted>September 24, 2019</last_update_submitted>
  <last_update_submitted_qc>September 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Aarhus University Hospital</investigator_affiliation>
    <investigator_full_name>Lars Christian Gormsen</investigator_full_name>
    <investigator_title>Senior Registrar, MD PhD</investigator_title>
  </responsible_party>
  <keyword>Type 2 diabetes</keyword>
  <keyword>Hepatic fatty acid oxidation</keyword>
  <keyword>Dyslipidemia</keyword>
  <keyword>Metformin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 4, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/56/NCT01729156/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Controls</title>
          <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
        </group>
        <group group_id="P3">
          <title>Metformin</title>
          <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Controls</title>
          <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
        </group>
        <group group_id="B3">
          <title>Metformin</title>
          <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="12"/>
            <count group_id="B4" value="36"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="6"/>
                    <measurement group_id="B2" value="60" spread="5"/>
                    <measurement group_id="B3" value="64" spread="5"/>
                    <measurement group_id="B4" value="62" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.3" spread="4.1"/>
                    <measurement group_id="B2" value="31.2" spread="4.3"/>
                    <measurement group_id="B3" value="30.3" spread="5.7"/>
                    <measurement group_id="B4" value="29.6" spread="4.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>HbA1C</title>
          <units>mmol/mmol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37" spread="3"/>
                    <measurement group_id="B2" value="45" spread="6"/>
                    <measurement group_id="B3" value="51" spread="6"/>
                    <measurement group_id="B4" value="44" spread="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Hepatic Fatty Acid Oxidation</title>
        <description>Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Hepatic Fatty Acid Oxidation</title>
          <description>Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET</description>
          <units>micromol/ml/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.052" spread="0.024"/>
                    <measurement group_id="O2" value="0.045" spread="0.024"/>
                    <measurement group_id="O3" value="0.042" spread="0.017"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hepatic Fatty Acid Reesterification</title>
        <description>Hepatic fatty acid reesterification assessed by C11-palmitate PET</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Hepatic Fatty Acid Reesterification</title>
          <description>Hepatic fatty acid reesterification assessed by C11-palmitate PET</description>
          <units>micromol/ml/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.134" spread="0.056"/>
                    <measurement group_id="O2" value="0.091" spread="0.035"/>
                    <measurement group_id="O3" value="0.113" spread="0.025"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hepatic Fatty Acid Uptake</title>
        <description>Hepatic fatty acid uptake assessed by C11-palmitate PET</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Hepatic Fatty Acid Uptake</title>
          <description>Hepatic fatty acid uptake assessed by C11-palmitate PET</description>
          <units>micromol/ml/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.186" spread="0.067"/>
                    <measurement group_id="O2" value="0.137" spread="0.051"/>
                    <measurement group_id="O3" value="0.155" spread="0.029"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>VLDL-TG Secretion</title>
        <description>Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>VLDL-TG Secretion</title>
          <description>Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer</description>
          <units>micromol/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48" spread="30"/>
                    <measurement group_id="O2" value="83" spread="49"/>
                    <measurement group_id="O3" value="71" spread="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Whole Body Glucose Rd</title>
        <description>Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Sandoz&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Whole Body Glucose Rd</title>
          <description>Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics</description>
          <units>mg/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.74" spread="0.29"/>
                    <measurement group_id="O2" value="1.30" spread="0.31"/>
                    <measurement group_id="O3" value="1.78" spread="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fatty Acid Turnover</title>
        <description>Fatty acid turnover assessed as whole body C11-palmitate turnover</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>Fatty Acid Turnover</title>
          <description>Fatty acid turnover assessed as whole body C11-palmitate turnover</description>
          <units>micromol/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="464" spread="127"/>
                    <measurement group_id="O2" value="476" spread="149"/>
                    <measurement group_id="O3" value="559" spread="295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VLDL-TG Oxidation</title>
        <description>VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Controls</title>
            <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
          </group>
          <group group_id="O3">
            <title>Metformin</title>
            <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
          </group>
        </group_list>
        <measure>
          <title>VLDL-TG Oxidation</title>
          <description>VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath</description>
          <units>percentage of 14C-VLDL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29" spread="5"/>
                    <measurement group_id="O2" value="30" spread="7"/>
                    <measurement group_id="O3" value="27" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During the 90 days trial</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Healthy Controls</title>
          <description>Healthy controls receiving 1000 mg metformin twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo&#xD;
Placebo: 2 tablets twice daily in 3 months</description>
        </group>
        <group group_id="E3">
          <title>Metformin</title>
          <description>Metformin &quot;Teva&quot;, 1000 mg twice daily for 3 months&#xD;
Metformin: 1000 mg metformin twice daily in 3 months</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal uncomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fractured vertebral column</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Lars C. Gormsen, Consultant</name_or_title>
      <organization>Department of Nuclear Medicine &amp; PET Centre, Aarhus University Hospital</organization>
      <phone>004578456260</phone>
      <email>lars.christian.gormsen@clin.au.dk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01729156
org study id: C11palmitatMetformin
nct id: NCT01729156
lead sponsor: 
has dmc: Yes
Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism.
      Whereas there is general agreement that the blood glucose lowering effect of metformin
      results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug
      lowers blood triglyceride concentration. There are indications that it enhances hepatic free
      fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as
      very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily
      accessible for sampling in humans and data on the clinical effects of metformin in the liver
      are therefore lacking. This may change due to the increasing use of the positron emission
      tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a
      fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.

      Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic
      lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.

      Design: Randomized, placebo controlled, double-blind parallel study with patients receiving
      either metformin or placebo. A control group of BMI and age-matched non-diabetic individuals
      will receive metformin for 3 months.

      Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing
      hepatic fatty acid oxidation
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Hepatic Fatty Acid Oxidation
time frame: 90 days
description: Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
measure: Hepatic Fatty Acid Reesterification
time frame: 90 days
description: Hepatic fatty acid reesterification assessed by C11-palmitate PET
measure: Hepatic Fatty Acid Uptake
time frame: 90 days
description: Hepatic fatty acid uptake assessed by C11-palmitate PET
measure: VLDL-TG Secretion
time frame: 90 days
description: Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
measure: Whole Body Glucose Rd
time frame: 90 days
description: Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics
measure: Fatty Acid Turnover
time frame: 90 days
description: Fatty acid turnover assessed as whole body C11-palmitate turnover
measure: VLDL-TG Oxidation
time frame: 90 days
description: VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath
arm group label: Healthy controls
arm group type: Other
description: Healthy controls receiving 1000 mg metformin twice daily for 3 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
arm group label: Metformin
arm group type: Active Comparator
description: Metformin "Sandoz", 1000 mg twice daily for 3 months
intervention type: Drug
intervention name: Metformin
description: 1000 mg metformin twice daily in 3 months
arm group label: Healthy controls
arm group label: Metformin
other name: Metformin "Sandoz" 500 mg
intervention type: Drug
intervention name: Placebo
description: 2 tablets twice daily in 3 months
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lars C Gormsen, MD PhD
role: Principal Investigator
affiliation: Aarhus University Hospital
responsible party type: Sponsor-Investigator
investigator affiliation: Aarhus University Hospital
investigator full name: Lars Christian Gormsen
investigator title: Senior Registrar, MD PhD
mesh term: Diabetes Mellitus, Type 2
mesh term: Dyslipidemias
mesh term: Metformin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 