<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/NCT03305211</url>
  </required_header>
  <id_info>
    <org_study_id>2017-49</org_study_id>
    <nct_id>NCT03305211</nct_id>
  </id_info>
  <brief_title>Biological Collection in Nephrology for the Study of the Links Between Kidney Disease, Immunity System and Cardiovascular Complications</brief_title>
  <acronym>NéphroMIC²</acronym>
  <official_title>Biological Collection in Nephrology for the Study of the Links Between Kidney Disease, Immunity System and Cardiovascular Complications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</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>
      The NephoMIC project is a biological collection in patients of Nephrology, allowing the study&#xD;
      of the links between kidney diseases, Immunity system and Cardiovascular complications.&#xD;
&#xD;
      Its aim is to allow the development of a translational research on the theme of &quot;Systemic&#xD;
      Nephrology&quot;, which concerns both renal complications of autoimmune and inflammatory diseases,&#xD;
      and systemic complications of patients with kidney disease, linked to both a state of&#xD;
      immunosuppression and an increased risk of cardiovascular complications.&#xD;
&#xD;
      It is based on the proximity between the Clinical investigation Center (CIC) of the hospital,&#xD;
      where the samples are received, techniqued and preserved, and the Center of Nephrology and&#xD;
      Renal Transplantation of the hospital.&#xD;
&#xD;
      The collection includes blood samples (whole blood, serum, plasma, total blood RNA, PBMC&#xD;
      cells), and urine samples (fresh urine).&#xD;
&#xD;
      Participation in the collection is particularly recommended for patients who require a&#xD;
      medical renal biopsy in the Nephrology Department. Other well-phenotyped patients&#xD;
      (well-defined renal disease diagnosis) may also participate in NephroMIC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Kidney damage to systemic lupus erythematosus (SLE), anti-cytoplasmic neutrophil cytoplasmic&#xD;
      (ANCA) vasculitis or systemic amyloidosis, expose patients to:&#xD;
&#xD;
        -  a risk of renal insufficiency, which depends on the severity of the attack, the delay in&#xD;
           the initiation of treatment, and the possible occurrence of relapses, which may leave&#xD;
           fibrous sequelae and lead to the development of insufficiency chronic renal disease&#xD;
           (CKD)&#xD;
&#xD;
        -  a risk of immunosuppression and infectious complications, linked to the renal&#xD;
           insufficiency itself or to the toxicity of immunosuppressive treatments aimed at&#xD;
           controlling renal disease&#xD;
&#xD;
        -  an increased risk of cardiovascular complications, linked on the one hand to the&#xD;
           activity of the systemic disease and to the endothelial dysfunction it may entail, and&#xD;
           on the other hand to the cardiovascular risk associated with the IRC .&#xD;
&#xD;
      Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, evolving in relapses&#xD;
      interrupted by periods of remission. Renal impairment of SLE is common (20-30% of patients in&#xD;
      Europe) [1] and severe [2], with an impact on patient survival [3] and a risk of progression&#xD;
      to chronic renal insufficiency (IRC). Thus, nearly 40% of patients with severe form develop&#xD;
      IRC [4], and 5-10% have terminal IRC at 10 years [5,6]. The classification of renal&#xD;
      involvement according to the International Society of Nephrology / Renal Pathology Society&#xD;
      (ISN / RPS) [7] distinguishes active proliferative forms, requiring immunosuppressive therapy&#xD;
      [8], nonproliferative or purely chronic forms. However, renal biopsy remains an invasive&#xD;
      procedure [9], which can hardly be repeatedly performed, let alone pre-emptively, although&#xD;
      the onset of tissue damage precedes the emergence of clinically detectable proteinuria [10] .&#xD;
      In addition, the response of proliferative lupus nephropathy to immunosuppressive therapy is&#xD;
      difficult to predict. The progression in treatment is favorable in 70 to 80% of patients with&#xD;
      proliferative form, but 20-30% are refractory to the standard treatment, while others retain&#xD;
      important chronic lesions leading to chronic renal insufficiency.&#xD;
&#xD;
      There is therefore a crucial need for non-invasive biomarkers to identify lupus patients at&#xD;
      risk for developing renal disease and to predict the severity of histological involvement and&#xD;
      response to immunosuppressive therapy.&#xD;
&#xD;
      The investigators believe that the pathophysiological complexity of lupus nephropathy can not&#xD;
      be summarized to a single biomarker, and that a global &quot;omic&quot; approach could capture this&#xD;
      complexity or identify new pathways.&#xD;
&#xD;
      The blood transcriptome study is a non-invasive and usable approach in clinical research,&#xD;
      which allowed 10 years ago to identify the signature of lupus interferon (IFN) [11], which&#xD;
      had not been detected in serum of patients, and led to new therapeutic pathways. The&#xD;
      complexity and size of pan-genomic transcriptomic data may be an obstacle to their analysis&#xD;
      and interpretation [12]. Using a modular approach to reduce the size of transcriptomic blood&#xD;
      glucose data and facilitate their interpretation, the investigators were able to show the&#xD;
      gradation of the interferon signature during lupus [13], and describe the link between&#xD;
      neutrophil modular signature and renal impairment of lupus [14].&#xD;
&#xD;
      In addition, the search for noninvasive urinary biomarkers to avoid or limit biopsy&#xD;
      indications in the NL, or to predict the response to IS treatment to early adapt the&#xD;
      intensity, is of great interest. The current PeptiduLUP study is being conducted to determine&#xD;
      the diagnostic and prognostic value of urinary peptidoma analysis during lupus nephropathy.&#xD;
      The study of the urinary peptidome could make it possible to refine the indications of renal&#xD;
      biopsy in the renal involvement of the lupus.&#xD;
&#xD;
      In addition, there is an increased cardiovascular risk in patients with chronic renal failure&#xD;
      (CKD). Our team has demonstrated that the uremic toxins that accumulate in the IRC patients&#xD;
      are agonists of the AhR transmission factor and induce endothelial dysfunction with&#xD;
      development of a pro-thrombotic [15] and pro-inflammatory phenotype [16] ]. During lupus or&#xD;
      vasculitis at ANCA, the risk of cardiovascular complications increases as renal function&#xD;
      deteriorates [17,18], while in parallel the risk of immunological outbreak of the disease&#xD;
      decreases [19,18]. , 20]. The investigators believe that activation of AhR by uremic toxins&#xD;
      may be involved both in increasing the cardiovascular risk of these patients and in&#xD;
      inhibiting the autoimmune response.&#xD;
&#xD;
      There is therefore a strong rationale for studying the links between kidney disease, immunity&#xD;
      and cardiovascular complications.&#xD;
&#xD;
      The expected results are the identification of new blood (transcriptomic) and urinary&#xD;
      (peptidomic) biomarkers for diagnostic and prognostic purposes during renal disease.&#xD;
      NephroMIC will also provide research fellowships on biomarkers during renal disease,&#xD;
      especially during systemic diseases with renal involvement. The NephroMIC collection will&#xD;
      also allow participation in collaborative Nephrology research projects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 15, 2017</start_date>
  <completion_date type="Anticipated">April 20, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>patients requiring renal biopsy for medical reasons</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood and urinary biomarkers in renal disease</measure>
    <time_frame>one day</time_frame>
    <description>biological assay</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Biological sample</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>biological sampling will be performed on patients requiring renal biopsy and well-phenotyped patients (diagnosis of renal disease)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>sample</intervention_name>
    <description>Participation in NephroMIC involves additional blood samples of 5 tubes (35 mL) and an additional sample of fresh urine.</description>
    <arm_group_label>Biological sample</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult Patient (&gt; 18 years)&#xD;
&#xD;
          -  Patient with renal disease&#xD;
&#xD;
          -  Patient who signed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant woman&#xD;
&#xD;
          -  Severe anemia (Hb &lt;7 g / dL)&#xD;
&#xD;
          -  Patient deprived of liberty&#xD;
&#xD;
          -  Patient not affiliated to a Social Security scheme&#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>Urielle DESALBRES</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique Hôpitaux de Marseille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Noémie JOURDE-CHICHE</last_name>
    <phone>04 91 38 30 42</phone>
    <email>noemie.jourde@ap-hm.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Assistance Publique des Hôpitaux de Marseille Hôpital de la Conception</name>
      <address>
        <city>Marseille</city>
        <zip>13354</zip>
        <country>France</country>
      </address>
    </facility>
    <contact>
      <last_name>Noémie JOURDE-CHICHE</last_name>
      <phone>04 91 38 30 42</phone>
      <email>noemie.jourde@ap-hm.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 4, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>October 6, 2017</last_update_submitted>
  <last_update_submitted_qc>October 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</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/NCT03305211
org study id: 2017-49
nct id: NCT03305211
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The NephoMIC project is a biological collection in patients of Nephrology, allowing the study
      of the links between kidney diseases, Immunity system and Cardiovascular complications.

      Its aim is to allow the development of a translational research on the theme of "Systemic
      Nephrology", which concerns both renal complications of autoimmune and inflammatory diseases,
      and systemic complications of patients with kidney disease, linked to both a state of
      immunosuppression and an increased risk of cardiovascular complications.

      It is based on the proximity between the Clinical investigation Center (CIC) of the hospital,
      where the samples are received, techniqued and preserved, and the Center of Nephrology and
      Renal Transplantation of the hospital.

      The collection includes blood samples (whole blood, serum, plasma, total blood RNA, PBMC
      cells), and urine samples (fresh urine).

      Participation in the collection is particularly recommended for patients who require a
      medical renal biopsy in the Nephrology Department. Other well-phenotyped patients
      (well-defined renal disease diagnosis) may also participate in NephroMIC.
Kidney damage to systemic lupus erythematosus (SLE), anti-cytoplasmic neutrophil cytoplasmic
      (ANCA) vasculitis or systemic amyloidosis, expose patients to:

        -  a risk of renal insufficiency, which depends on the severity of the attack, the delay in
           the initiation of treatment, and the possible occurrence of relapses, which may leave
           fibrous sequelae and lead to the development of insufficiency chronic renal disease
           (CKD)

        -  a risk of immunosuppression and infectious complications, linked to the renal
           insufficiency itself or to the toxicity of immunosuppressive treatments aimed at
           controlling renal disease

        -  an increased risk of cardiovascular complications, linked on the one hand to the
           activity of the systemic disease and to the endothelial dysfunction it may entail, and
           on the other hand to the cardiovascular risk associated with the IRC .

      Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, evolving in relapses
      interrupted by periods of remission. Renal impairment of SLE is common (20-30% of patients in
      Europe) [1] and severe [2], with an impact on patient survival [3] and a risk of progression
      to chronic renal insufficiency (IRC). Thus, nearly 40% of patients with severe form develop
      IRC [4], and 5-10% have terminal IRC at 10 years [5,6]. The classification of renal
      involvement according to the International Society of Nephrology / Renal Pathology Society
      (ISN / RPS) [7] distinguishes active proliferative forms, requiring immunosuppressive therapy
      [8], nonproliferative or purely chronic forms. However, renal biopsy remains an invasive
      procedure [9], which can hardly be repeatedly performed, let alone pre-emptively, although
      the onset of tissue damage precedes the emergence of clinically detectable proteinuria [10] .
      In addition, the response of proliferative lupus nephropathy to immunosuppressive therapy is
      difficult to predict. The progression in treatment is favorable in 70 to 80% of patients with
      proliferative form, but 20-30% are refractory to the standard treatment, while others retain
      important chronic lesions leading to chronic renal insufficiency.

      There is therefore a crucial need for non-invasive biomarkers to identify lupus patients at
      risk for developing renal disease and to predict the severity of histological involvement and
      response to immunosuppressive therapy.

      The investigators believe that the pathophysiological complexity of lupus nephropathy can not
      be summarized to a single biomarker, and that a global "omic" approach could capture this
      complexity or identify new pathways.

      The blood transcriptome study is a non-invasive and usable approach in clinical research,
      which allowed 10 years ago to identify the signature of lupus interferon (IFN) [11], which
      had not been detected in serum of patients, and led to new therapeutic pathways. The
      complexity and size of pan-genomic transcriptomic data may be an obstacle to their analysis
      and interpretation [12]. Using a modular approach to reduce the size of transcriptomic blood
      glucose data and facilitate their interpretation, the investigators were able to show the
      gradation of the interferon signature during lupus [13], and describe the link between
      neutrophil modular signature and renal impairment of lupus [14].

      In addition, the search for noninvasive urinary biomarkers to avoid or limit biopsy
      indications in the NL, or to predict the response to IS treatment to early adapt the
      intensity, is of great interest. The current PeptiduLUP study is being conducted to determine
      the diagnostic and prognostic value of urinary peptidoma analysis during lupus nephropathy.
      The study of the urinary peptidome could make it possible to refine the indications of renal
      biopsy in the renal involvement of the lupus.

      In addition, there is an increased cardiovascular risk in patients with chronic renal failure
      (CKD). Our team has demonstrated that the uremic toxins that accumulate in the IRC patients
      are agonists of the AhR transmission factor and induce endothelial dysfunction with
      development of a pro-thrombotic [15] and pro-inflammatory phenotype [16] ]. During lupus or
      vasculitis at ANCA, the risk of cardiovascular complications increases as renal function
      deteriorates [17,18], while in parallel the risk of immunological outbreak of the disease
      decreases [19,18]. , 20]. The investigators believe that activation of AhR by uremic toxins
      may be involved both in increasing the cardiovascular risk of these patients and in
      inhibiting the autoimmune response.

      There is therefore a strong rationale for studying the links between kidney disease, immunity
      and cardiovascular complications.

      The expected results are the identification of new blood (transcriptomic) and urinary
      (peptidomic) biomarkers for diagnostic and prognostic purposes during renal disease.
      NephroMIC will also provide research fellowships on biomarkers during renal disease,
      especially during systemic diseases with renal involvement. The NephroMIC collection will
      also allow participation in collaborative Nephrology research projects.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: patients requiring renal biopsy for medical reasons
primary purpose: Other
masking: None (Open Label)
measure: Blood and urinary biomarkers in renal disease
time frame: one day
description: biological assay
arm group label: Biological sample
arm group type: Other
description: biological sampling will be performed on patients requiring renal biopsy and well-phenotyped patients (diagnosis of renal disease)
intervention type: Other
intervention name: sample
description: Participation in NephroMIC involves additional blood samples of 5 tubes (35 mL) and an additional sample of fresh urine.
arm group label: Biological sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Urielle DESALBRES
role: Study Director
affiliation: Assistance Publique Hôpitaux de Marseille
last name: Noémie JOURDE-CHICHE
phone: 04 91 38 30 42
email: noemie.jourde@ap-hm.fr
facility: 
contact: 
country: France
responsible party type: Sponsor
mesh term: Kidney Diseases