<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/NCT03830255</url>
  </required_header>
  <id_info>
    <org_study_id>FWA000017585</org_study_id>
    <nct_id>NCT03830255</nct_id>
  </id_info>
  <brief_title>Effect of Genetic Polymorphism on Calcineurin Inhibitors Levels in Egyptian Renal Transplant Patients</brief_title>
  <official_title>Calcineurin Inhibitors Among Egyptian Renal Transplant Patients: a Pharmacognetic Based Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helwan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helwan University</source>
  <oversight_info>
    <has_dmc>No</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>
      Renal transplantation is the treatment of choice for patients with end-stage renal disease&#xD;
      (ESRD). Calcineurin Inhibitors tacrolimus and cyclosporine are the principle&#xD;
      immunosuppressive agents administered to solid organ transplant recipients to prevent and&#xD;
      treat allograft rejection.&#xD;
&#xD;
      The aim of the present study is to detect the incidence of some selected genetic polymorphism&#xD;
      in Egyptian renal transplant population and investigate the influence of these genetic&#xD;
      polymorphism (SNPs )on Cyclosporine and Tacrolimus blood concentration. In addition to detect&#xD;
      the association between these genetic polymorphism variants and patients' clinical outcome&#xD;
      after transplantation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid&#xD;
      organ transplant recipients to prevent and treat allograft rejection.They both exert their&#xD;
      immunosppressive action by inhibiting the calcinurein in T-lymphoctes.&#xD;
      Subsequently,Cyclosporin and tacrolimus are both metabolic substrates for cytochrome P450&#xD;
      (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells by the&#xD;
      P-glycoprotein (ABCB1) efflux pump. Different expression of CYP3A4, CYP3A5 and P-glycoprotein&#xD;
      causes patient to-patient variability in the absorption, metabolism and tissue distribution&#xD;
      of calcineurin inhibitors. This different expression is likely to be at least partially the&#xD;
      result of mutations in the genes encoding for these enzymes and drug transporter. This may&#xD;
      lead to variable drug concentrations within the systemic circulation and at target sites,&#xD;
      influencing drug efficacy. Moreover, it will influence the individual's susceptibility to&#xD;
      drug interactions and drug toxicity&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">March 29, 2020</completion_date>
  <primary_completion_date type="Actual">October 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>CYP enzymes genetic polymorphism and calcineurin inhibitors drug levels</measure>
    <time_frame>3 months</time_frame>
    <description>Association of CP3A4 and CYP3A5 genetic polymorphism SNPs on Cyclosporine and Tacrolimus blood concentration</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">143</enrollment>
  <condition>Renal Transplantation</condition>
  <arm_group>
    <arm_group_label>Renal Transplant patients treated with cyclosporine</arm_group_label>
    <description>Detecting the genetic polymorphism affecting cyclosporine level</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Renal Transplant patients treated with tacrolimus</arm_group_label>
    <description>Detecting the genetic polymorphism affecting tacrolimus level</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood samples will be collected and stored in - 80°C environment for DNA&#xD;
      extraction by DNA extraction kit according to manufacturer recommendation&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Renal Transplant Patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Kidney transplant patients.&#xD;
&#xD;
          2. Treatment with calcineurin inhibitors (CNI) either Cyclosporine (Neoral®) or&#xD;
             Tacrolimus (Prograf®).&#xD;
&#xD;
          3. Absence of medication known to interact with CNI&#xD;
&#xD;
          4. Age18 years and more&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient who experience acute rejection, graft failure.&#xD;
&#xD;
          2. Medications that interact with Calcineurin Inhibitors.&#xD;
&#xD;
          3. Pregnant or nursing women.&#xD;
&#xD;
          4. Patients who decline to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Magdy El Sharkawy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ain Shams University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Abdel hameed Ibrahim Mohamed Ebid, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Helwan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Neama Lotfy, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ain sham university</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohamed Adel, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Helwan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ain shams university specialized hospital</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>February 1, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 5, 2019</study_first_posted>
  <last_update_submitted>March 25, 2021</last_update_submitted>
  <last_update_submitted_qc>March 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Misr International University</investigator_affiliation>
    <investigator_full_name>Dina Ahmed Mohamed Ali Ismail</investigator_full_name>
    <investigator_title>Lecturer Assistant at Clinical Pharmacy and Pharmacy Practice department</investigator_title>
  </responsible_party>
  <keyword>Renal Transplantation</keyword>
  <keyword>Genetic Polymorphism</keyword>
  <keyword>CYP3A5</keyword>
  <keyword>CYP3A4</keyword>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03830255
org study id: FWA000017585
nct id: NCT03830255
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Renal transplantation is the treatment of choice for patients with end-stage renal disease
      (ESRD). Calcineurin Inhibitors tacrolimus and cyclosporine are the principle
      immunosuppressive agents administered to solid organ transplant recipients to prevent and
      treat allograft rejection.

      The aim of the present study is to detect the incidence of some selected genetic polymorphism
      in Egyptian renal transplant population and investigate the influence of these genetic
      polymorphism (SNPs )on Cyclosporine and Tacrolimus blood concentration. In addition to detect
      the association between these genetic polymorphism variants and patients' clinical outcome
      after transplantation.
Tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid
      organ transplant recipients to prevent and treat allograft rejection.They both exert their
      immunosppressive action by inhibiting the calcinurein in T-lymphoctes.
      Subsequently,Cyclosporin and tacrolimus are both metabolic substrates for cytochrome P450
      (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells by the
      P-glycoprotein (ABCB1) efflux pump. Different expression of CYP3A4, CYP3A5 and P-glycoprotein
      causes patient to-patient variability in the absorption, metabolism and tissue distribution
      of calcineurin inhibitors. This different expression is likely to be at least partially the
      result of mutations in the genes encoding for these enzymes and drug transporter. This may
      lead to variable drug concentrations within the systemic circulation and at target sites,
      influencing drug efficacy. Moreover, it will influence the individual's susceptibility to
      drug interactions and drug toxicity
observational model: Cohort
time perspective: Prospective
measure: CYP enzymes genetic polymorphism and calcineurin inhibitors drug levels
time frame: 3 months
description: Association of CP3A4 and CYP3A5 genetic polymorphism SNPs on Cyclosporine and Tacrolimus blood concentration
arm group label: Renal Transplant patients treated with cyclosporine
description: Detecting the genetic polymorphism affecting cyclosporine level
arm group label: Renal Transplant patients treated with tacrolimus
description: Detecting the genetic polymorphism affecting tacrolimus level
Peripheral blood samples will be collected and stored in - 80°C environment for DNA
      extraction by DNA extraction kit according to manufacturer recommendation
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Magdy El Sharkawy, MD
role: Principal Investigator
affiliation: Ain Shams University
last name: Abdel hameed Ibrahim Mohamed Ebid, PhD
role: Study Director
affiliation: Helwan University
last name: Neama Lotfy, MD
role: Study Director
affiliation: Ain sham university
last name: Mohamed Adel, PhD
role: Study Director
affiliation: Helwan University
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Misr International University
investigator full name: Dina Ahmed Mohamed Ali Ismail
investigator title: Lecturer Assistant at Clinical Pharmacy and Pharmacy Practice department
sharing ipd: Undecided