<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/NCT01726764</url>
  </required_header>
  <id_info>
    <org_study_id>AKF-382</org_study_id>
    <nct_id>NCT01726764</nct_id>
  </id_info>
  <brief_title>Interaction Between St John's Wort and Metformin?</brief_title>
  <official_title>Is There a Pharmacokinetic Interaction Between St John's Wort and Metformin?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Southern Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of the study is to examine the difference of the pharmacokinetics of metformin with&#xD;
      and without a 3 weeks pretreatment of St John's Wort. Furthermore secondary objectives&#xD;
      include changes in GLP-1, C-peptide, serum-insulin and plasma-glucose during an oral glucose&#xD;
      tolerance test, changes in OCT1 mRNA in plasma and changes in leptin and lipid-profile&#xD;
      following this possible interaction.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">June 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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Area Under Curve (AUC) 0-24h of metformin</measure>
    <time_frame>Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion</time_frame>
    <description>Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Oral glucose tolerance test (OGTT)</measure>
    <time_frame>During the first 2 hours of each metformin ingestion</time_frame>
    <description>Changes in: Plasma-glucose, serum-insulin, glucagon-like peptide 1 (GLP-1) and connecting-peptides (C-peptides) during the oral glucose tolerance test, measured at 0, 0.5, 1, 1.5 and 2 hours after metformin ingestion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of metformin</measure>
    <time_frame>Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion, which will be used to determine the pharmacokinetic parameters mentioned below</time_frame>
    <description>Determination of other pharmacokinetic parameters of metformin such as clearance (CL), absorption fraction (F), distribution volume (V), the minimum concentration at steady state (Css,min), elimination half life (T 1/2) etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in messenger RiboNucleic Acid (mRNA)</measure>
    <time_frame>Will be measured 4 times: At inclusion (t=0 on that day), at t=0 in both periods and minimum 3 weeks after finalization of the study (t=0 on that day)</time_frame>
    <description>Changes in mRNA encoding OCT1 will be measured at 4 different time points to give an insight to the importance of St John's Wort effect on the OCT1 production</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Hypericin/hyperforin</measure>
    <time_frame>At t=0 in 2nd period</time_frame>
    <description>If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>7 days of pretreatment with metformin before full pharmacokinetics and other goals are investigated.&#xD;
Minimum 1 week of washout after this period. 3 weeks of pretreatment with St John's Wort and the last 7 days metformin is ingested again, and the same effect parameters as described above is performed again</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>St John's Wort</intervention_name>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <arm_group_label>Metformin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men aged 18-64 years&#xD;
&#xD;
          -  Homozygous for common genetic variants in the genes organic cation transporter 1/2&#xD;
             (OCT1/OCT2)&#xD;
&#xD;
          -  Normal values of biomarkers accounting for: Liver and kidney function, and normal&#xD;
             blood glucose&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic alcohol abuse&#xD;
&#xD;
          -  Hypersensitivity to metformin or St John's Wort&#xD;
&#xD;
          -  Daily intake of drugs requiring prescription&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per Damkier, MD ph.d.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Tore B. Stage, M.Sc. Pharm</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern Denmark</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kim Brøsen, Professor, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Southern Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark</name>
      <address>
        <city>Odense</city>
        <zip>DK-5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <last_update_submitted>December 2, 2014</last_update_submitted>
  <last_update_submitted_qc>December 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Southern Denmark</investigator_affiliation>
    <investigator_full_name>Tore B. Stage</investigator_full_name>
    <investigator_title>M.Sc. Pharm</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</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/NCT01726764
org study id: AKF-382
nct id: NCT01726764
lead sponsor: 
has dmc: No
The goal of the study is to examine the difference of the pharmacokinetics of metformin with
      and without a 3 weeks pretreatment of St John's Wort. Furthermore secondary objectives
      include changes in GLP-1, C-peptide, serum-insulin and plasma-glucose during an oral glucose
      tolerance test, changes in OCT1 mRNA in plasma and changes in leptin and lipid-profile
      following this possible interaction.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Change in Area Under Curve (AUC) 0-24h of metformin
time frame: Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion
description: Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort
measure: Oral glucose tolerance test (OGTT)
time frame: During the first 2 hours of each metformin ingestion
description: Changes in: Plasma-glucose, serum-insulin, glucagon-like peptide 1 (GLP-1) and connecting-peptides (C-peptides) during the oral glucose tolerance test, measured at 0, 0.5, 1, 1.5 and 2 hours after metformin ingestion.
measure: Pharmacokinetics of metformin
time frame: Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion, which will be used to determine the pharmacokinetic parameters mentioned below
description: Determination of other pharmacokinetic parameters of metformin such as clearance (CL), absorption fraction (F), distribution volume (V), the minimum concentration at steady state (Css,min), elimination half life (T 1/2) etc.
measure: Change in messenger RiboNucleic Acid (mRNA)
time frame: Will be measured 4 times: At inclusion (t=0 on that day), at t=0 in both periods and minimum 3 weeks after finalization of the study (t=0 on that day)
description: Changes in mRNA encoding OCT1 will be measured at 4 different time points to give an insight to the importance of St John's Wort effect on the OCT1 production
measure: Hypericin/hyperforin
time frame: At t=0 in 2nd period
description: If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin
arm group label: Metformin
arm group type: Experimental
description: 7 days of pretreatment with metformin before full pharmacokinetics and other goals are investigated.
Minimum 1 week of washout after this period. 3 weeks of pretreatment with St John's Wort and the last 7 days metformin is ingested again, and the same effect parameters as described above is performed again
intervention type: Other
intervention name: St John's Wort
arm group label: Metformin
intervention type: Drug
intervention name: Metformin
arm group label: Metformin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Per Damkier, MD ph.d.
role: Principal Investigator
affiliation: University of Southern Denmark
last name: Tore B. Stage, M.Sc. Pharm
role: Principal Investigator
affiliation: University of Southern Denmark
last name: Kim Brøsen, Professor, MD
role: Study Director
affiliation: University of Southern Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: University of Southern Denmark
investigator full name: Tore B. Stage
investigator title: M.Sc. Pharm
mesh term: Depression
mesh term: Metformin