<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/NCT04428398</url>
  </required_header>
  <id_info>
    <org_study_id>PRE-FLARED</org_study_id>
    <nct_id>NCT04428398</nct_id>
  </id_info>
  <brief_title>Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive ANCA-associated Glomerulonephritis</brief_title>
  <acronym>PRE-FLARED</acronym>
  <official_title>Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Charite University, Berlin, Germany</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>
      Urinary CD4+ and CD8+ T lymphocytes may predict renal flares in patients with inactive&#xD;
      ANCA-associated vasculitis and thus serve as early non-invasive biomarkers. Urine samples of&#xD;
      patients with inactive renal ANCA-vasculitis will be analysed by flow cytometry and compared&#xD;
      to clinical outcome after 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Data of previous studies have shown that counts of urinary T lymphocyte subsets correlate&#xD;
      with disease activity in several immunological renal diseases, e.g. ANCA-associated&#xD;
      glomerulonephritis. Thus, study authors hypothesise that CD4+, respectively CD8+, T effector&#xD;
      memory lymphocytes found in urine samples of patients with inactive ANCA-vasculitis predict&#xD;
      subsequent renal flares. Therefore, quantification of these cellular subsets might reliably&#xD;
      predict relapse of ANCA associated glomerulonephritis at an early stage. In a prospective&#xD;
      experimental study urine of patients with ANCA-vasculitis and no renal involvement or&#xD;
      patients in renal remission will be analysed by flow cytometry. After 6 months of&#xD;
      observation, clinical outcome and potential renal relapse will be determined and correlated&#xD;
      to initial T lymphocyte count.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Actual">September 1, 2021</completion_date>
  <primary_completion_date type="Actual">September 1, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Prediction of renal relapse after six months depending initial CD4+ count</measure>
    <time_frame>6 months</time_frame>
    <description>relapse defined as Birmingham Vasculitis Activity Score (BVAS) &gt; 1 + at least one renal element or&#xD;
intensified treatment regime (Prednisolon equivalent &gt; 20 mg/d or novel induction treatment with Rituximab or Cyclophosphamide)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prediction of renal relapse after six months depending initial CD8+ count</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets</measure>
    <time_frame>6 months</time_frame>
    <description>Subsets: T effector memory cells (CD45RO+/CCR7-)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prediction of renal relapse after 12 months depending initial CD4+ count</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prediction of renal relapse after 12 months depending initial CD8+ count</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets</measure>
    <time_frame>12 months</time_frame>
    <description>Subsets: T effector memory cells (CD45RO+/CCR7-)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Glomerulonephritis Acute</condition>
  <arm_group>
    <arm_group_label>No renal involvement</arm_group_label>
    <description>Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Renal remission</arm_group_label>
    <description>Patient with ANCA-vasculitis in renal remission</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Analysis of urine samples with flow cytometry</intervention_name>
    <description>Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes.&#xD;
T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326</description>
    <arm_group_label>No renal involvement</arm_group_label>
    <arm_group_label>Renal remission</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      urine samples (approximately 60 mL per patient)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients in medical wards or at outpatient departments of 2 facilities:&#xD;
&#xD;
          -  Charité - Universitätsmedizin Berlin&#xD;
&#xD;
          -  Helios Klinikum Berlin-Buch&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosed ANCA-associated vasculitis (clinical diagnosis of granulomatosis with&#xD;
             polyangiitis, eosinophilic granulomatosis with polyangiitis or microscopic&#xD;
             polyangiitis consistent with the Chapel-Hill consensus definitions AND positive test&#xD;
             for proteinase 3-ANCA or myeloperoxidase-ANCA)&#xD;
&#xD;
          -  no currently active renal involvement (defined as BVAS = 0 with exception of hematuria&#xD;
             or proteinuria as signs of renal scars)&#xD;
&#xD;
          -  written and informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  urinary tract infection&#xD;
&#xD;
          -  active menstrual bleeding&#xD;
&#xD;
          -  current therapy with rituximab&#xD;
&#xD;
          -  active renal involvement&#xD;
&#xD;
          -  other active renal disease (e.g. diabetic nephropathy)&#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>Philipp Enghard</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Adrian Schreiber, PD Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helios Klinikum Berlin-Buch</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Goceroglu A, Berden AE, Fiocco M, Flossmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noel LH, Rasmussen N, Waldherr R, Walsh M, Bruijn JA, Jayne DR, Bajema IM; European Vasculitis Society (EUVAS). ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse. PLoS One. 2016 Dec 14;11(12):e0165402. doi: 10.1371/journal.pone.0165402. eCollection 2016.</citation>
    <PMID>27973575</PMID>
  </reference>
  <reference>
    <citation>Menez S, Hruskova Z, Scott J, Cormican S, Chen M, Salama AD, Alasfar S, Little MA, Safrankova H, Honsova E, Tesar V, Geetha D. Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis. Am J Nephrol. 2018;48(6):465-471. doi: 10.1159/000494840. Epub 2018 Nov 23.</citation>
    <PMID>30472700</PMID>
  </reference>
  <reference>
    <citation>Cordova-Sanchez BM, Mejia-Vilet JM, Morales-Buenrostro LE, Loyola-Rodriguez G, Uribe-Uribe NO, Correa-Rotter R. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clin Rheumatol. 2016 Jul;35(7):1805-16. doi: 10.1007/s10067-016-3195-z. Epub 2016 Feb 6.</citation>
    <PMID>26852317</PMID>
  </reference>
  <reference>
    <citation>Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.</citation>
    <PMID>23475982</PMID>
  </reference>
  <reference>
    <citation>Abdulahad WH, Kallenberg CG, Limburg PC, Stegeman CA. Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Sep;60(9):2830-8. doi: 10.1002/art.24747.</citation>
    <PMID>19714581</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>March 8, 2022</last_update_submitted>
  <last_update_submitted_qc>March 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Philipp Enghard</investigator_full_name>
    <investigator_title>PD Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis</keyword>
  <keyword>Pauci-Immune Glomerulonephritis</keyword>
  <keyword>urinary biomarker</keyword>
  <keyword>Churg-Strauss Syndrome</keyword>
  <keyword>Microscopic Polyangiitis</keyword>
  <keyword>Granulomatosis with Polyangiitis</keyword>
  <keyword>effector memory T lymphocytes</keyword>
  <keyword>prediction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glomerulonephritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT04428398
org study id: PRE-FLARED
nct id: NCT04428398
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Urinary CD4+ and CD8+ T lymphocytes may predict renal flares in patients with inactive
      ANCA-associated vasculitis and thus serve as early non-invasive biomarkers. Urine samples of
      patients with inactive renal ANCA-vasculitis will be analysed by flow cytometry and compared
      to clinical outcome after 6 months.
Data of previous studies have shown that counts of urinary T lymphocyte subsets correlate
      with disease activity in several immunological renal diseases, e.g. ANCA-associated
      glomerulonephritis. Thus, study authors hypothesise that CD4+, respectively CD8+, T effector
      memory lymphocytes found in urine samples of patients with inactive ANCA-vasculitis predict
      subsequent renal flares. Therefore, quantification of these cellular subsets might reliably
      predict relapse of ANCA associated glomerulonephritis at an early stage. In a prospective
      experimental study urine of patients with ANCA-vasculitis and no renal involvement or
      patients in renal remission will be analysed by flow cytometry. After 6 months of
      observation, clinical outcome and potential renal relapse will be determined and correlated
      to initial T lymphocyte count.
observational model: Case-Only
time perspective: Prospective
measure: Prediction of renal relapse after six months depending initial CD4+ count
time frame: 6 months
description: relapse defined as Birmingham Vasculitis Activity Score (BVAS) > 1 + at least one renal element or
intensified treatment regime (Prednisolon equivalent > 20 mg/d or novel induction treatment with Rituximab or Cyclophosphamide)
measure: Prediction of renal relapse after six months depending initial CD8+ count
time frame: 6 months
measure: Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets
time frame: 6 months
description: Subsets: T effector memory cells (CD45RO+/CCR7-)
measure: Prediction of renal relapse after 12 months depending initial CD4+ count
time frame: 12 months
measure: Prediction of renal relapse after 12 months depending initial CD8+ count
time frame: 12 months
measure: Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets
time frame: 12 months
description: Subsets: T effector memory cells (CD45RO+/CCR7-)
arm group label: No renal involvement
description: Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history
arm group label: Renal remission
description: Patient with ANCA-vasculitis in renal remission
intervention type: Diagnostic Test
intervention name: Analysis of urine samples with flow cytometry
description: Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes.
T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326
arm group label: No renal involvement
arm group label: Renal remission
urine samples (approximately 60 mL per patient)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Philipp Enghard
role: Principal Investigator
affiliation: Charite University, Berlin, Germany
last name: Adrian Schreiber, PD Dr. med.
role: Principal Investigator
affiliation: Charite University, Berlin, Germany
facility: 
facility: 
country: Germany
citation: Goceroglu A, Berden AE, Fiocco M, Flossmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noel LH, Rasmussen N, Waldherr R, Walsh M, Bruijn JA, Jayne DR, Bajema IM; European Vasculitis Society (EUVAS). ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse. PLoS One. 2016 Dec 14;11(12):e0165402. doi: 10.1371/journal.pone.0165402. eCollection 2016.
PMID: 27973575
citation: Menez S, Hruskova Z, Scott J, Cormican S, Chen M, Salama AD, Alasfar S, Little MA, Safrankova H, Honsova E, Tesar V, Geetha D. Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis. Am J Nephrol. 2018;48(6):465-471. doi: 10.1159/000494840. Epub 2018 Nov 23.
PMID: 30472700
citation: Cordova-Sanchez BM, Mejia-Vilet JM, Morales-Buenrostro LE, Loyola-Rodriguez G, Uribe-Uribe NO, Correa-Rotter R. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clin Rheumatol. 2016 Jul;35(7):1805-16. doi: 10.1007/s10067-016-3195-z. Epub 2016 Feb 6.
PMID: 26852317
citation: Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.
PMID: 23475982
citation: Abdulahad WH, Kallenberg CG, Limburg PC, Stegeman CA. Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Sep;60(9):2830-8. doi: 10.1002/art.24747.
PMID: 19714581
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Philipp Enghard
investigator title: PD Dr. med.
mesh term: Glomerulonephritis
sharing ipd: Yes