<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/NCT04439708</url>
  </required_header>
  <id_info>
    <org_study_id>C18-08</org_study_id>
    <secondary_id>2018-A02099-46</secondary_id>
    <nct_id>NCT04439708</nct_id>
  </id_info>
  <brief_title>Biomarkers and Choroidal Neovascularization</brief_title>
  <acronym>BioNéoRet</acronym>
  <official_title>Biomarkers Analysis of Mineralocortoid Receptor Activation in the Serum and Ocular Fluid of Patients With Choroidal Neovascularization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</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 aim of the study is to find biomarkers in the blood and aqueous humor of patients with&#xD;
      type 1 choroidal neovascularization and correlate them with the response to anti-VEGF&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Age-related macular degeneration (AMD) is the most frequent cause of blindness in&#xD;
      industrialized countries. Multiple molecular pathways have been implicated in the&#xD;
      pathogenesis of choroidal neovascularization (CNV). Currently, the treatment relies on&#xD;
      neutralization of VEGF (Vascular Endothelial Growth Factor). However some patients have an&#xD;
      incomplete response to anti-VEGF treatment. A recent study suggested the implication of the&#xD;
      mineralocorticoid receptor pathway in the formation of CNV.&#xD;
&#xD;
      The study (of investigators) aim is to evaluate the concentation of metabolites of MR pathway&#xD;
      in the blood and aqueous humor of patients with CNV and compared them with patients without&#xD;
      CNV in order to increase our understanding of CNV pathogenesis and find potential biomarker&#xD;
      of response to anti-VEGF treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 15, 2020</start_date>
  <completion_date type="Anticipated">April 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>biomarker analysis in blood and aqueous humor of patients with neovascularization and controls</measure>
    <time_frame>24 months</time_frame>
    <description>Biomarker concentrations (pg/ml) will be evaluated with ELISA (Enzyme Linked ImmunoSorbent Assay).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>biomarker analysis in blood and aqueous humor of patients with neovascularization and controls</measure>
    <time_frame>24 months</time_frame>
    <description>Biomarker concentrations (pg/ml) will be evaluated with Mulitplex Biorad.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>biomarkers and treatment response</measure>
    <time_frame>24 months</time_frame>
    <description>Correlation between biomarker level and the response to anti-VEGF treatment</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Choroidal Neovascularization</condition>
  <condition>Mineralocorticoid Excess</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <description>Patients with choroidal neovascularization in the context of age-related macular degeneration or central serous chorioretinopathy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <description>Control group : patients without choroidal neovascularization</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood and aqueous humor biomarker of treatment response</intervention_name>
    <description>Blood analyses and aqueous humor analysis</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood and aqueous humor samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Group 1 : patients with type 1 choroidal neovascularization Group 2: patients without&#xD;
        choroidal neovascularization before ocular surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients of group 1:&#xD;
&#xD;
          -  Patients with type 1 choroidal neovascularization in a context of central serous&#xD;
             chorioretinoathy or age related macular degeneration&#xD;
&#xD;
          -  Patients without intravitreal injection or last intravitreal injection &gt; 3 months&#xD;
&#xD;
          -  Informed signed consent&#xD;
&#xD;
        Patients of group 2:&#xD;
&#xD;
          -  Patients without choroidal neovascularization&#xD;
&#xD;
          -  Patients with intraocular surgery (cataract or vitrectomy surgery)&#xD;
&#xD;
          -  Signed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Myocardial infarction &lt; 12 months&#xD;
&#xD;
          -  Chronic renal failure&#xD;
&#xD;
          -  Inflammatory disease&#xD;
&#xD;
          -  Infectious disease :HIV, viral hepatitis, tuberculosis&#xD;
&#xD;
          -  Type 1 or 2 Diabetes&#xD;
&#xD;
          -  Patients treated by mineralocorticoid antagonist treatment.&#xD;
&#xD;
          -  Type 2 or 3 choroidal neovascularization&#xD;
&#xD;
          -  Pregnant woman&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Francine Behar-Cohen, Dr</last_name>
    <phone>01 44 27 81 64</phone>
    <email>francine.cohen@aphp.fr</email>
  </overall_contact>
  <reference>
    <citation>Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Sasaki M, Tsubota K, Ozawa Y. Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration. Br J Ophthalmol. 2014 Sep;98(9):1186-91. doi: 10.1136/bjophthalmol-2013-304670. Epub 2014 Apr 7.</citation>
    <PMID>24711658</PMID>
  </reference>
  <reference>
    <citation>Kersten E, Paun CC, Schellevis RL, Hoyng CB, Delcourt C, Lengyel I, Peto T, Ueffing M, Klaver CCW, Dammeier S, den Hollander AI, de Jong EK. Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration. Surv Ophthalmol. 2018 Jan-Feb;63(1):9-39. doi: 10.1016/j.survophthal.2017.05.003. Epub 2017 May 15.</citation>
    <PMID>28522341</PMID>
  </reference>
  <reference>
    <citation>Rezar-Dreindl S, Sacu S, Eibenberger K, Pollreisz A, Buhl W, Georgopoulos M, Krall C, Weigert G, Schmidt-Erfurth U. The Intraocular Cytokine Profile and Therapeutic Response in Persistent Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4144-50. doi: 10.1167/iovs.16-19772.</citation>
    <PMID>27537264</PMID>
  </reference>
  <reference>
    <citation>Zhao M, Mantel I, Gelize E, Li X, Xie X, Arboleda A, Seminel M, Levy-Boukris R, Dernigoghossian M, Prunotto A, Andrieu-Soler C, Rivolta C, Canonica J, Naud MC, Lechner S, Farman N, Bravo-Osuna I, Herrero-Vanrell R, Jaisser F, Behar-Cohen F. Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration. Nat Commun. 2019 Jan 21;10(1):369. doi: 10.1038/s41467-018-08125-6.</citation>
    <PMID>30664640</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>March 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>June 17, 2020</last_update_submitted>
  <last_update_submitted_qc>June 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>central serous chorioretinopathy</keyword>
  <keyword>age related macular degeneration</keyword>
  <keyword>biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choroidal Neovascularization</mesh_term>
    <mesh_term>Hyperaldosteronism</mesh_term>
    <mesh_term>Neovascularization, Pathologic</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/NCT04439708
org study id: C18-08
secondary id: 2018-A02099-46
nct id: NCT04439708
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to find biomarkers in the blood and aqueous humor of patients with
      type 1 choroidal neovascularization and correlate them with the response to anti-VEGF
      treatment.
Age-related macular degeneration (AMD) is the most frequent cause of blindness in
      industrialized countries. Multiple molecular pathways have been implicated in the
      pathogenesis of choroidal neovascularization (CNV). Currently, the treatment relies on
      neutralization of VEGF (Vascular Endothelial Growth Factor). However some patients have an
      incomplete response to anti-VEGF treatment. A recent study suggested the implication of the
      mineralocorticoid receptor pathway in the formation of CNV.

      The study (of investigators) aim is to evaluate the concentation of metabolites of MR pathway
      in the blood and aqueous humor of patients with CNV and compared them with patients without
      CNV in order to increase our understanding of CNV pathogenesis and find potential biomarker
      of response to anti-VEGF treatment.
observational model: Other
time perspective: Prospective
measure: biomarker analysis in blood and aqueous humor of patients with neovascularization and controls
time frame: 24 months
description: Biomarker concentrations (pg/ml) will be evaluated with ELISA (Enzyme Linked ImmunoSorbent Assay).
measure: biomarker analysis in blood and aqueous humor of patients with neovascularization and controls
time frame: 24 months
description: Biomarker concentrations (pg/ml) will be evaluated with Mulitplex Biorad.
measure: biomarkers and treatment response
time frame: 24 months
description: Correlation between biomarker level and the response to anti-VEGF treatment
arm group label: Group 1
description: Patients with choroidal neovascularization in the context of age-related macular degeneration or central serous chorioretinopathy
arm group label: Group 2
description: Control group : patients without choroidal neovascularization
intervention type: Other
intervention name: Blood and aqueous humor biomarker of treatment response
description: Blood analyses and aqueous humor analysis
arm group label: Group 1
arm group label: Group 2
blood and aqueous humor samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Francine Behar-Cohen, Dr
phone: 01 44 27 81 64
email: francine.cohen@aphp.fr
citation: Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Sasaki M, Tsubota K, Ozawa Y. Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration. Br J Ophthalmol. 2014 Sep;98(9):1186-91. doi: 10.1136/bjophthalmol-2013-304670. Epub 2014 Apr 7.
PMID: 24711658
citation: Kersten E, Paun CC, Schellevis RL, Hoyng CB, Delcourt C, Lengyel I, Peto T, Ueffing M, Klaver CCW, Dammeier S, den Hollander AI, de Jong EK. Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration. Surv Ophthalmol. 2018 Jan-Feb;63(1):9-39. doi: 10.1016/j.survophthal.2017.05.003. Epub 2017 May 15.
PMID: 28522341
citation: Rezar-Dreindl S, Sacu S, Eibenberger K, Pollreisz A, Buhl W, Georgopoulos M, Krall C, Weigert G, Schmidt-Erfurth U. The Intraocular Cytokine Profile and Therapeutic Response in Persistent Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2016 Aug 1;57(10):4144-50. doi: 10.1167/iovs.16-19772.
PMID: 27537264
citation: Zhao M, Mantel I, Gelize E, Li X, Xie X, Arboleda A, Seminel M, Levy-Boukris R, Dernigoghossian M, Prunotto A, Andrieu-Soler C, Rivolta C, Canonica J, Naud MC, Lechner S, Farman N, Bravo-Osuna I, Herrero-Vanrell R, Jaisser F, Behar-Cohen F. Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration. Nat Commun. 2019 Jan 21;10(1):369. doi: 10.1038/s41467-018-08125-6.
PMID: 30664640
responsible party type: Sponsor
mesh term: Choroidal Neovascularization
mesh term: Hyperaldosteronism
mesh term: Neovascularization, Pathologic