<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/NCT01681693</url>
  </required_header>
  <id_info>
    <org_study_id>6113</org_study_id>
    <nct_id>NCT01681693</nct_id>
  </id_info>
  <brief_title>Effect of Genetic Variants in MATE1 and OCT3 on the Pharmacodynamics of Metformin in African Americans</brief_title>
  <acronym>#6113</acronym>
  <official_title>Effect of Genetic Variants in MATE1 and OCT3 Transporters on the Pharmacodynamics of Metformin in African Americans With Type II Diabetes Mellitus.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study is part of a large multi-investigator grant to look at the pharmacogenetics&#xD;
      of a number of membrane transporters. The investigators will study individuals with&#xD;
      particular genotypes of the human organic cation transporter, (hOCT3), and the multidrug and&#xD;
      toxin extrusion transporter, MATE1 to test the hypothesis that genetic variation in hOCT3 and&#xD;
      hMATE1 are associated with variation in the pharmacokinetics and/or pharmacodynamics of the&#xD;
      antidiabetic agent, metformin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To investigate the potential association of polymorphic genetic variants MATE1 and OCT3 with&#xD;
      altered response to metformin, a genotype to phenotype strategy is employed. Specifically,&#xD;
      the investigators will evaluate this hypothesis in African-Americans, a population which has&#xD;
      a high incidence of type 2 diabetes and which has high variant allele frequencies (44.5% for&#xD;
      MATE1-66T&gt;C and 11.3% in OCT3-81G&gt;delGA) relative to other ethic groups. To assess the&#xD;
      effects of these variants on metformin response, the investigators will measure metformin&#xD;
      renal clearance (pharmacokinetics of metformin), and plasma glucose and insulin levels&#xD;
      (pharmacodynamic response) in healthy and diabetic patients who carry either the reference or&#xD;
      variant alleles.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2010</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</primary_completion_date>
  <phase>Phase 1</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal Clearance of the Metformin</measure>
    <time_frame>24 hours post-dose</time_frame>
    <description>To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered pharmacokinetics of metformin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma glucose</measure>
    <time_frame>0, 15, 30, 45, 60, 90, 120, 180 minutes after glucose administration</time_frame>
    <description>To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered glucose lowering response to metformin.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Healthy</condition>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be given an oral dose of metformin once per day for two days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Subjects will be given an oral dose of metformin once per day for two days.</description>
    <arm_group_label>Metformin</arm_group_label>
    <other_name>GLUCOPHAGE</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects self-identify racial background, identify themselves, parents and four&#xD;
             grandparents as African American&#xD;
&#xD;
          -  Subject status is healthy volunteer from t In the event that diabetes is indicated in&#xD;
             a normal subject based on OGTT results, we will notify the patients' primary care&#xD;
             physician. he SOPHIE cohort OR diagnosis of T2DM based on American Diabetes&#xD;
             Association (ADA) criteria&#xD;
&#xD;
          -  Subjects over 18 years old and below 60 years&#xD;
&#xD;
          -  Subjects who are healthy on the basis of medical history, physical examinations and&#xD;
             laboratory tests if healthy volunteer from SOPHIE&#xD;
&#xD;
          -  Subjects who agree with the written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to confirm African-American ethnicity&#xD;
&#xD;
          -  Under 18 years old&#xD;
&#xD;
          -  Pregnant or lactating women (female subjects will have a urine pregnancy test at the&#xD;
             screening visit).&#xD;
&#xD;
          -  Prior history of any allergic reaction to metformin&#xD;
&#xD;
          -  Has a risk of congestive heart failure requiring pharmacologic treatment (medical&#xD;
             history)&#xD;
&#xD;
          -  Has a prior history of renal* or hepatic dysfunction (renal and hepatic function will&#xD;
             be evaluated based on screening blood tests conducted prior to study enrollment)&#xD;
&#xD;
          -  Risk of urinary or gastric retention or narrow-angle glaucoma (by medical history&#xD;
             examination)&#xD;
&#xD;
          -  Impaired renal function (e.g as suggested by abnormal creatinine clearance, eGFR &lt;60&#xD;
             or serum creatinine &gt;1.4 mg/dl in females and &gt;1.5 mg/dl in males) which may also&#xD;
             result from conditions such as cardiovascular collapse (shock), acute myocardial&#xD;
             infarction (heart attack), and septicemia, abnormal heart rhythms (tachyarrhythmias;&#xD;
             heart beat &gt; 100 beats per minute).&#xD;
&#xD;
          -  Impaired hepatic function (&gt; 1.5 times the upper limit of normal)&#xD;
&#xD;
          -  Evidence of anemia (hemoglobin &lt;10 g)&#xD;
&#xD;
          -  Taking a medication that could confound study results, such as known substrates or&#xD;
             inhibitors of OCT3 and MATE1, such as cimetidine.&#xD;
&#xD;
          -  They do not provide consent to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathleen M Giacomini, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <last_update_submitted>October 21, 2014</last_update_submitted>
  <last_update_submitted_qc>October 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 23, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</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/NCT01681693
org study id: 6113
nct id: NCT01681693
lead sponsor: 
has dmc: Yes
The current study is part of a large multi-investigator grant to look at the pharmacogenetics
      of a number of membrane transporters. The investigators will study individuals with
      particular genotypes of the human organic cation transporter, (hOCT3), and the multidrug and
      toxin extrusion transporter, MATE1 to test the hypothesis that genetic variation in hOCT3 and
      hMATE1 are associated with variation in the pharmacokinetics and/or pharmacodynamics of the
      antidiabetic agent, metformin.
To investigate the potential association of polymorphic genetic variants MATE1 and OCT3 with
      altered response to metformin, a genotype to phenotype strategy is employed. Specifically,
      the investigators will evaluate this hypothesis in African-Americans, a population which has
      a high incidence of type 2 diabetes and which has high variant allele frequencies (44.5% for
      MATE1-66T>C and 11.3% in OCT3-81G>delGA) relative to other ethic groups. To assess the
      effects of these variants on metformin response, the investigators will measure metformin
      renal clearance (pharmacokinetics of metformin), and plasma glucose and insulin levels
      (pharmacodynamic response) in healthy and diabetic patients who carry either the reference or
      variant alleles.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Renal Clearance of the Metformin
time frame: 24 hours post-dose
description: To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered pharmacokinetics of metformin.
measure: Plasma glucose
time frame: 0, 15, 30, 45, 60, 90, 120, 180 minutes after glucose administration
description: To test whether individuals with genetic variants of transporters OCT3 and MATE1 exhibit altered glucose lowering response to metformin.
arm group label: Metformin
arm group type: Experimental
description: Subjects will be given an oral dose of metformin once per day for two days.
intervention type: Drug
intervention name: Metformin
description: Subjects will be given an oral dose of metformin once per day for two days.
arm group label: Metformin
other name: GLUCOPHAGE
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Kathleen M Giacomini, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Metformin