<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/NCT02252237</url>
  </required_header>
  <id_info>
    <org_study_id>2014-A00987-40</org_study_id>
    <nct_id>NCT02252237</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Glucocorticoids in Children (GLUCOPED)</brief_title>
  <acronym>GLUCOPED</acronym>
  <official_title>Study of Pharmacokinetic Variability of Glucocorticoids in Children</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine individual susceptibility factors (drug&#xD;
      interactions, genetic factors such as enzyme polymorphism…) to explain wide interindividual&#xD;
      variability towards corticosteroids (prednisone, prednisolone, methylprednisolone,&#xD;
      hydrocortisone) in children, which could establish a base for therapeutic monitoring.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Corticosteroids are widely used in children. A large interindividual variability exists&#xD;
      concerning both efficacity and tolerance. Pharmacokinetic is poorly known.&#xD;
&#xD;
      A knowledge of individual susceptibility factors would allow to better adapt therapy in each&#xD;
      case.&#xD;
&#xD;
      Drugs evaluated here are used in routine care in children and will be prescribed according to&#xD;
      department practices concerning treated disease. Medical checks will be done during usual&#xD;
      follow-up. Several features will be collected: reason of treatment, drug chosen and&#xD;
      prescription modalities, observance, concomitant treatments, side effects, clinical&#xD;
      examination, photography, score… Blood samples will be performed at different interval during&#xD;
      usual biological follow-up. Three samples per patient will be required for pharmacokinetic&#xD;
      and pharmacogenetic.&#xD;
&#xD;
      170 children under prednisone/prednisolone,130 under methylprednisolone, and 100 children&#xD;
      under hydrocortisone will be recruited in four pediatric medical departments:&#xD;
      immuno-hematology, nephrology,dermatology, and pediatric neurology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 3, 2014</start_date>
  <completion_date type="Anticipated">July 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2025</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>Composite of Pharmacokinetic parameter for Prednisone, Prednisolone, Methylprednisolone, hydrocortisone</measure>
    <time_frame>24 months</time_frame>
    <description>Assessed by:&#xD;
Volume of distribution of creatinine&#xD;
Creatinine clearance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Side effects</measure>
    <time_frame>24 months</time_frame>
    <description>Ferryman and Gallwey score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects</measure>
    <time_frame>24 months</time_frame>
    <description>Dermaphot® score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of genetic polymorphism of proteins taking part in glucocorticoids metabolism</measure>
    <time_frame>24 months</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">146</enrollment>
  <condition>Children Receiving Prednisone or Prednisolone or Methylprednisolone or Hydrocortisone</condition>
  <arm_group>
    <arm_group_label>Children with glucocorticoids</arm_group_label>
    <description>Children receiving Prednisone or Prednisolone or Methylprednisolone Pharmacokinetic</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pharmacokinetic</intervention_name>
    <description>Blood sample of 2 ml at enrolment and then at following visits. Buccal cell collection swab</description>
    <arm_group_label>Children with glucocorticoids</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Buccal cell collection swab&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Children receiving glucocorticoids (Prednisone or Prednisolone or Methylprednisolone or&#xD;
        hydrocortisone) are recruited in Immuno-hematological unit, dermatological unit, in&#xD;
        pediatric nephrological unit, pediatric intensive care unit, or pediatric neurology unit&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  receiving Prednisone or Prednisolone or Methylprednisolone or hydrocortisone&#xD;
&#xD;
          -  recruited in Immuno-hematological unit, dermatological unit, in pediatric&#xD;
             nephrological unit, pediatric intensive care unit, or pediatric neurology unit&#xD;
&#xD;
          -  parental agreement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  parental refusal&#xD;
&#xD;
          -  inability to take a blood sample&#xD;
&#xD;
          -  inhaled corticoids intake in the 3 previous days&#xD;
&#xD;
          -  topical corticoids intake in the 3 previous days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Marc Tréluyer, MD-PhD</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AP-HP Necker</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Bartoszek M, Brenner AM, Szefler SJ. Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Clin Pharmacol Ther. 1987 Oct;42(4):424-32. doi: 10.1038/clpt.1987.173.</citation>
    <PMID>3665340</PMID>
  </reference>
  <reference>
    <citation>Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8. doi: 10.1073/pnas.97.7.3473.</citation>
    <PMID>10716719</PMID>
  </reference>
  <reference>
    <citation>Jamroziak K, Mlynarski W, Balcerczak E, Mistygacz M, Trelinska J, Mirowski M, Bodalski J, Robak T. Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol. 2004 May;72(5):314-21. doi: 10.1111/j.1600-0609.2004.00228.x.</citation>
    <PMID>15059065</PMID>
  </reference>
  <reference>
    <citation>Gatti G, Perucca E, Frigo GM, Notarangelo LD, Barberis L, Martini A. Pharmacokinetics of prednisone and its metabolite prednisolone in children with nephrotic syndrome during the active phase and in remission. Br J Clin Pharmacol. 1984 Apr;17(4):423-31. doi: 10.1111/j.1365-2125.1984.tb02367.x.</citation>
    <PMID>6721988</PMID>
  </reference>
  <reference>
    <citation>Miller PF, Bowmer CJ, Wheeldon J, Brocklebank JT. Pharmacokinetics of prednisolone in children with nephrosis. Arch Dis Child. 1990 Feb;65(2):196-200. doi: 10.1136/adc.65.2.196.</citation>
    <PMID>2317067</PMID>
  </reference>
  <reference>
    <citation>Petersen KB, Jusko WJ, Rasmussen M, Schmiegelow K. Population pharmacokinetics of prednisolone in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2003 Jun;51(6):465-73. doi: 10.1007/s00280-003-0602-3. Epub 2003 Apr 16.</citation>
    <PMID>12698270</PMID>
  </reference>
  <reference>
    <citation>Faure C, Andre J, Pelatan C, Munck A, Giraud M, Cezard JP, Jacqz-Aigrain E. Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission. Eur J Clin Pharmacol. 1998 Sep;54(7):555-60. doi: 10.1007/s002280050512.</citation>
    <PMID>9832298</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>September 20, 2022</last_update_submitted>
  <last_update_submitted_qc>September 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Prednisone</keyword>
  <keyword>Prednisolone</keyword>
  <keyword>Methylprednisolone</keyword>
  <keyword>Glucocorticoids</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>hydrocortisone</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/NCT02252237
org study id: 2014-A00987-40
nct id: NCT02252237
lead sponsor: 
has dmc: No
The purpose of this study is to determine individual susceptibility factors (drug
      interactions, genetic factors such as enzyme polymorphism…) to explain wide interindividual
      variability towards corticosteroids (prednisone, prednisolone, methylprednisolone,
      hydrocortisone) in children, which could establish a base for therapeutic monitoring.
Corticosteroids are widely used in children. A large interindividual variability exists
      concerning both efficacity and tolerance. Pharmacokinetic is poorly known.

      A knowledge of individual susceptibility factors would allow to better adapt therapy in each
      case.

      Drugs evaluated here are used in routine care in children and will be prescribed according to
      department practices concerning treated disease. Medical checks will be done during usual
      follow-up. Several features will be collected: reason of treatment, drug chosen and
      prescription modalities, observance, concomitant treatments, side effects, clinical
      examination, photography, score… Blood samples will be performed at different interval during
      usual biological follow-up. Three samples per patient will be required for pharmacokinetic
      and pharmacogenetic.

      170 children under prednisone/prednisolone,130 under methylprednisolone, and 100 children
      under hydrocortisone will be recruited in four pediatric medical departments:
      immuno-hematology, nephrology,dermatology, and pediatric neurology.
observational model: Cohort
time perspective: Prospective
measure: Composite of Pharmacokinetic parameter for Prednisone, Prednisolone, Methylprednisolone, hydrocortisone
time frame: 24 months
description: Assessed by:
Volume of distribution of creatinine
Creatinine clearance
measure: Side effects
time frame: 24 months
description: Ferryman and Gallwey score
measure: Side effects
time frame: 24 months
description: Dermaphot® score
measure: Analysis of genetic polymorphism of proteins taking part in glucocorticoids metabolism
time frame: 24 months
arm group label: Children with glucocorticoids
description: Children receiving Prednisone or Prednisolone or Methylprednisolone Pharmacokinetic
intervention type: Biological
intervention name: Pharmacokinetic
description: Blood sample of 2 ml at enrolment and then at following visits. Buccal cell collection swab
arm group label: Children with glucocorticoids
Buccal cell collection swab
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jean-Marc Tréluyer, MD-PhD
role: Study Director
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
citation: Bartoszek M, Brenner AM, Szefler SJ. Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy. Clin Pharmacol Ther. 1987 Oct;42(4):424-32. doi: 10.1038/clpt.1987.173.
PMID: 3665340
citation: Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8. doi: 10.1073/pnas.97.7.3473.
PMID: 10716719
citation: Jamroziak K, Mlynarski W, Balcerczak E, Mistygacz M, Trelinska J, Mirowski M, Bodalski J, Robak T. Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol. 2004 May;72(5):314-21. doi: 10.1111/j.1600-0609.2004.00228.x.
PMID: 15059065
citation: Gatti G, Perucca E, Frigo GM, Notarangelo LD, Barberis L, Martini A. Pharmacokinetics of prednisone and its metabolite prednisolone in children with nephrotic syndrome during the active phase and in remission. Br J Clin Pharmacol. 1984 Apr;17(4):423-31. doi: 10.1111/j.1365-2125.1984.tb02367.x.
PMID: 6721988
citation: Miller PF, Bowmer CJ, Wheeldon J, Brocklebank JT. Pharmacokinetics of prednisolone in children with nephrosis. Arch Dis Child. 1990 Feb;65(2):196-200. doi: 10.1136/adc.65.2.196.
PMID: 2317067
citation: Petersen KB, Jusko WJ, Rasmussen M, Schmiegelow K. Population pharmacokinetics of prednisolone in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2003 Jun;51(6):465-73. doi: 10.1007/s00280-003-0602-3. Epub 2003 Apr 16.
PMID: 12698270
citation: Faure C, Andre J, Pelatan C, Munck A, Giraud M, Cezard JP, Jacqz-Aigrain E. Pharmacokinetics of intravenous methylprednisolone and oral prednisone in paediatric patients with inflammatory bowel disease during the acute phase and in remission. Eur J Clin Pharmacol. 1998 Sep;54(7):555-60. doi: 10.1007/s002280050512.
PMID: 9832298
responsible party type: Sponsor
sharing ipd: No