<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/NCT03267225</url>
  </required_header>
  <id_info>
    <org_study_id>D-VZR_2015_3</org_study_id>
    <nct_id>NCT03267225</nct_id>
  </id_info>
  <brief_title>Genetic Determinants of Clindamycin/Rifampin Interaction</brief_title>
  <acronym>CLINDA-RIFAM</acronym>
  <official_title>Study on the Genetic Determinants of Clindamycin/Rifampin Interaction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr Valerie ZELLER</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondation Ophtalmologique Adolphe de Rothschild</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Groupe Hospitalier Diaconesses Croix Saint-Simon</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Main objective- To study the influence of the polymorphisms of nuclear receptor proteins&#xD;
      pregnane X receptor (PXR), Liver X receptor alpha (LXRα), and Cytochrome P450 (CYP450) on the&#xD;
      clindamycin clearance during clindamycin/rifampin combination therapy.&#xD;
&#xD;
      Secondary objectives To study the influence of these polymorphisms on clindamycin clearance,&#xD;
      before combination therapy with rifampin (clindamycin monotherapy) To study the influence of&#xD;
      these polymorphisms on CYP450 activity before combination therapy with rifampin (clindamycin&#xD;
      monotherapy) To study the influence of these polymorphisms on the increase of CYP450 activity&#xD;
      after clindamycin/rifampin combination therapy To study the difference between the expected&#xD;
      and observed clindamycin serum concentrations after dosage adjustment, in patients with&#xD;
      clindamycin dosage adjustment after combination therapy with rifampin&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be informed on the study during their hospitalisation in the unit for&#xD;
      the treatment of bone and joint infection by the medical doctor. If they agree to participate&#xD;
      in the study, the following samples will be performed :&#xD;
&#xD;
        -  After at least 24 hours of clindamycin therapy and before combination therapy with&#xD;
           rifampin:&#xD;
&#xD;
             -  1 urine sample (5 mL) for CYP 450 activity phenotyping&#xD;
&#xD;
             -  1 blood sample (5 mL on ethylenediaminetetraacetic acid (EDTA) tubes) for measuring&#xD;
                clindamycin serum concentration and genotyping&#xD;
&#xD;
        -  After ten days of clindamycin-rifampin combination therapy:&#xD;
&#xD;
             -  1 urine sample (5 mL) for CYP 450 activity phenotyping&#xD;
&#xD;
             -  1 blood sample (5 mL on EDTA tubes) for measuring clindamycin serum concentration&#xD;
                and genotyping&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2016</start_date>
  <completion_date type="Actual">April 15, 2021</completion_date>
  <primary_completion_date type="Actual">April 15, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy</measure>
    <time_frame>10 days after onset of clindamycin/rifampin combination therapy</time_frame>
    <description>Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance after combination clindamycin-rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)</measure>
    <time_frame>One to four days after onset of clindamycin therapy and before starting rifampin therapy</time_frame>
    <description>Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance before rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin</measure>
    <time_frame>One to four days after onset of clindamycin therapy and before starting rifampin therapy</time_frame>
    <description>Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity before combination therapy with rifampin will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy</measure>
    <time_frame>10 days after onset of clindamycin/rifampin combination therapy</time_frame>
    <description>Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity after combination with rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.</measure>
    <time_frame>10 days after onset of clindamycin/rifampin combination therapy</time_frame>
    <description>The gap between the predicted and observed clindamycin serum concentrations will be quantified by MPE (Mean Prediction Errors) and RMSE (Root Mean Square Prediction Errors). Dosage adjustment will be considered predictive of the concentration if MPE and RMSE are &lt; 20 %.</description>
  </secondary_outcome>
  <enrollment type="Actual">84</enrollment>
  <condition>VA Drug Interaction</condition>
  <eligibility>
    <study_pop>
      <textblock>
        patient treated for a bone or joint infection with a clindamycin/rifampin combination&#xD;
        therapy, for at least 10 days&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  bone or joint infection&#xD;
&#xD;
          -  aged ≥ 18 years old&#xD;
&#xD;
          -  treatment with clindamycin/rifampin combination therapy &gt; 10 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  prescription of another treatment with potential action on CYP450&#xD;
&#xD;
          -  pregnant or breast feeding patient&#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>Valérie Zeller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>GH Diaconesses Croix Saint Simon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Groupe Hospitalier Diaconesses Croix Saint Simon</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 9, 2016</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Groupe Hospitalier Diaconesses Croix Saint-Simon</investigator_affiliation>
    <investigator_full_name>Dr Valerie ZELLER</investigator_full_name>
    <investigator_title>MD, principal investigator</investigator_title>
  </responsible_party>
  <keyword>drug interaction</keyword>
  <keyword>genetic polymorphism</keyword>
  <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/NCT03267225
org study id: D-VZR_2015_3
nct id: NCT03267225
lead sponsor: 
collaborator: 
has dmc: Yes
Main objective- To study the influence of the polymorphisms of nuclear receptor proteins
      pregnane X receptor (PXR), Liver X receptor alpha (LXRα), and Cytochrome P450 (CYP450) on the
      clindamycin clearance during clindamycin/rifampin combination therapy.

      Secondary objectives To study the influence of these polymorphisms on clindamycin clearance,
      before combination therapy with rifampin (clindamycin monotherapy) To study the influence of
      these polymorphisms on CYP450 activity before combination therapy with rifampin (clindamycin
      monotherapy) To study the influence of these polymorphisms on the increase of CYP450 activity
      after clindamycin/rifampin combination therapy To study the difference between the expected
      and observed clindamycin serum concentrations after dosage adjustment, in patients with
      clindamycin dosage adjustment after combination therapy with rifampin
Eligible patients will be informed on the study during their hospitalisation in the unit for
      the treatment of bone and joint infection by the medical doctor. If they agree to participate
      in the study, the following samples will be performed :

        -  After at least 24 hours of clindamycin therapy and before combination therapy with
           rifampin:

             -  1 urine sample (5 mL) for CYP 450 activity phenotyping

             -  1 blood sample (5 mL on ethylenediaminetetraacetic acid (EDTA) tubes) for measuring
                clindamycin serum concentration and genotyping

        -  After ten days of clindamycin-rifampin combination therapy:

             -  1 urine sample (5 mL) for CYP 450 activity phenotyping

             -  1 blood sample (5 mL on EDTA tubes) for measuring clindamycin serum concentration
                and genotyping
observational model: Other
time perspective: Prospective
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy
time frame: 10 days after onset of clindamycin/rifampin combination therapy
description: Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance after combination clindamycin-rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)
time frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
description: Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on clindamycin clearance before rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin
time frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
description: Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity before combination therapy with rifampin will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy
time frame: 10 days after onset of clindamycin/rifampin combination therapy
description: Impact of PXR, LXRα, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity after combination with rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.
measure: Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.
time frame: 10 days after onset of clindamycin/rifampin combination therapy
description: The gap between the predicted and observed clindamycin serum concentrations will be quantified by MPE (Mean Prediction Errors) and RMSE (Root Mean Square Prediction Errors). Dosage adjustment will be considered predictive of the concentration if MPE and RMSE are < 20 %.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Valérie Zeller, MD
role: Principal Investigator
affiliation: GH Diaconesses Croix Saint Simon
facility: 
country: France
responsible party type: Sponsor-Investigator
investigator affiliation: Groupe Hospitalier Diaconesses Croix Saint-Simon
investigator full name: Dr Valerie ZELLER
investigator title: MD, principal investigator
sharing ipd: No