<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/NCT02262065</url>
  </required_header>
  <id_info>
    <org_study_id>230-12</org_study_id>
    <nct_id>NCT02262065</nct_id>
  </id_info>
  <brief_title>Risk Factors for Enhanced Inflammation to Arthroplasty Wear Particles: Analysis of Cytokine Production and Polymorphisms</brief_title>
  <official_title>Individual Risk Factors for Enhanced Inflammation to Arthroplasty Wear Particles: Analysis of Cytokine Polymorphisms and in Vitro Cytokine Production to Wear Particles (Ceramic, Metal, XPE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Rostock</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assessment of cytokine polymorphisms in 100 patients with aseptic complications to&#xD;
      arthroplasty as compared to 100 symptom-free arthroplasty patients.&#xD;
&#xD;
      In selected patients additional in-vitro cytokine release assay with peripheral blood&#xD;
      mononuclear cells (PBMC) stimulated with different wear particles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A cytokine polymorphism analysis in 100 individuals with aseptic implant intolerance reaction&#xD;
      (patients of the implant allergy special ambulance) and in 100 asymptomatic patients with&#xD;
      implanted endoprostheses will be done. Furthermore, supplementary clinical data (such as type&#xD;
      of implant, hospital stay, discomfort), questionnaire-based history and a clinical score&#xD;
      (WOMAC score) are recorded. In the subgroup analysis in 10 patients of implant patients with&#xD;
      complaints with special found cytokine polymorphisms and 10 implant patients without problems&#xD;
      the cytokine response to particles in vitro will assessed.&#xD;
&#xD;
      Test parameters:&#xD;
&#xD;
        1. total collective:&#xD;
&#xD;
           the DNA of cryopreserved blood sample will be isolated. By polymerase chain reaction,&#xD;
           four different known polymorphisms will be analyzed, three IL-1B genes (IL-1B-3954&#xD;
           IL-1B-31, and IL-1B-511), and a IL-1ß receptor antagonist gene (IL -1-RN, intron 2&#xD;
           VNTR). Molecular analysis includes DNA isolation, polymerase chain reactions (PCR) and&#xD;
           gel electrophoresis.&#xD;
&#xD;
        2. Subgroup analysis:&#xD;
&#xD;
      Peripheral blood cells will be isolated from 10 implant patients with complications and 10&#xD;
      symptom-free persons and stimulated in cell culture with control stimuli, the IL-1ß-inducer&#xD;
      lipopolysaccharide (LPS) and ceramic particles (BIOLOX delta)*, CoCrMo particles and&#xD;
      XPE-particles** cultured separately or in combination. The secretion of IL-1ß and selected&#xD;
      proinflammatory cytokines will be measured. The methods include cell isolation by density&#xD;
      centrifugation and analysis of cell culture supernatants by a multiplex cytokine measurement&#xD;
      assay by flow cytometry.&#xD;
&#xD;
      * Supplied CeramTec&#xD;
&#xD;
      ** Generated and processed by the Working Group of the cooperation partner Prof. R. Bader&#xD;
      (University Hospital Rostock) in special carrier system for cell culture stimulation approach&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">February 22, 2019</completion_date>
  <primary_completion_date type="Actual">January 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Polymorphism frequency</measure>
    <time_frame>2 years</time_frame>
    <description>Frequency of 4 different cytokine polymorphisms will be assessed in the 2 study groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cytokine production</measure>
    <time_frame>1 year</time_frame>
    <description>Subgroup analysis: In vitro cytokine production of 20 patients with special polymorphism constellation will be analyzed after stimulation with particles.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">195</enrollment>
  <condition>Allergy</condition>
  <condition>Implants</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <description>Patients with suspected arthroplasty intolerance</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Patients with well tolerated arthroplasties</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples of 20 patients (subgroup analysis)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with arthroplasty:&#xD;
&#xD;
        A) without symptoms B) with aseptic complications&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  arthroplasty&#xD;
&#xD;
          -  over 18 years&#xD;
&#xD;
          -  no infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  inability to consent&#xD;
&#xD;
          -  malposition&#xD;
&#xD;
          -  infection&#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>Peter Thomas, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ludwig-Maximilians - University of Munich</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ludwig-Maximilians-University Munich, Dept. of Dermatology</name>
      <address>
        <city>Munich</city>
        <state>Bavaria</state>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>December 23, 2013</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>February 26, 2019</last_update_submitted>
  <last_update_submitted_qc>February 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>Peter Thomas</investigator_full_name>
    <investigator_title>Prof. Dr.</investigator_title>
  </responsible_party>
  <keyword>implant</keyword>
  <keyword>allergy</keyword>
  <keyword>particle</keyword>
  <keyword>cytokine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_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/NCT02262065
org study id: 230-12
nct id: NCT02262065
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Assessment of cytokine polymorphisms in 100 patients with aseptic complications to
      arthroplasty as compared to 100 symptom-free arthroplasty patients.

      In selected patients additional in-vitro cytokine release assay with peripheral blood
      mononuclear cells (PBMC) stimulated with different wear particles.
A cytokine polymorphism analysis in 100 individuals with aseptic implant intolerance reaction
      (patients of the implant allergy special ambulance) and in 100 asymptomatic patients with
      implanted endoprostheses will be done. Furthermore, supplementary clinical data (such as type
      of implant, hospital stay, discomfort), questionnaire-based history and a clinical score
      (WOMAC score) are recorded. In the subgroup analysis in 10 patients of implant patients with
      complaints with special found cytokine polymorphisms and 10 implant patients without problems
      the cytokine response to particles in vitro will assessed.

      Test parameters:

        1. total collective:

           the DNA of cryopreserved blood sample will be isolated. By polymerase chain reaction,
           four different known polymorphisms will be analyzed, three IL-1B genes (IL-1B-3954
           IL-1B-31, and IL-1B-511), and a IL-1ß receptor antagonist gene (IL -1-RN, intron 2
           VNTR). Molecular analysis includes DNA isolation, polymerase chain reactions (PCR) and
           gel electrophoresis.

        2. Subgroup analysis:

      Peripheral blood cells will be isolated from 10 implant patients with complications and 10
      symptom-free persons and stimulated in cell culture with control stimuli, the IL-1ß-inducer
      lipopolysaccharide (LPS) and ceramic particles (BIOLOX delta)*, CoCrMo particles and
      XPE-particles** cultured separately or in combination. The secretion of IL-1ß and selected
      proinflammatory cytokines will be measured. The methods include cell isolation by density
      centrifugation and analysis of cell culture supernatants by a multiplex cytokine measurement
      assay by flow cytometry.

      * Supplied CeramTec

      ** Generated and processed by the Working Group of the cooperation partner Prof. R. Bader
      (University Hospital Rostock) in special carrier system for cell culture stimulation approach
observational model: Case-Control
time perspective: Retrospective
measure: Polymorphism frequency
time frame: 2 years
description: Frequency of 4 different cytokine polymorphisms will be assessed in the 2 study groups.
measure: Cytokine production
time frame: 1 year
description: Subgroup analysis: In vitro cytokine production of 20 patients with special polymorphism constellation will be analyzed after stimulation with particles.
arm group label: Patients
description: Patients with suspected arthroplasty intolerance
arm group label: Controls
description: Patients with well tolerated arthroplasties
blood samples of 20 patients (subgroup analysis)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Peter Thomas, Prof. Dr.
role: Principal Investigator
affiliation: Ludwig-Maximilians - University of Munich
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: Peter Thomas
investigator title: Prof. Dr.
mesh term: Inflammation