<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/NCT02976194</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0186</org_study_id>
    <nct_id>NCT02976194</nct_id>
  </id_info>
  <brief_title>Intraocular Cytokine in Recurrence of Polypoidal Choroidal Vasculopathy</brief_title>
  <acronym>CyPov</acronym>
  <official_title>Intraocular Cytokine Changes in Recurrence of Polypoidal Choroidal Vasculopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pusan National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Pusan National University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Changes of intraocular cytokines including vascular endothelial growth factor (VEGF) will be&#xD;
      measured in recurrence of polypoidal choroidal vasculopathy (PCV) during treatment of&#xD;
      ranibizumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PCV is regarded as a subtype of age-related macular degeneration (ARMD), but has several&#xD;
      different features such as polypoidal terminal of new vessels, and relative resistance to&#xD;
      anti-VEGF treatment. Other cytokines then VEGF are thought to be associated with development&#xD;
      and progression of the disease. The aim of the this study is to investigate intraocular&#xD;
      cytokines related to recurrence of polypoidal choroidal vasculopathy. Aqueous humor will be&#xD;
      sampled from the anterior chamber at baseline, after loading injections of ranibizumab and at&#xD;
      recurrence. The concentration of various cytokines will be measured in the aqueous humor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 22, 2016</start_date>
  <completion_date type="Anticipated">January 2020</completion_date>
  <primary_completion_date type="Anticipated">November 2019</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of VEGF-A from 8 weeks to 20 weeks</measure>
    <time_frame>8 weeks and 20 weeks</time_frame>
    <description>Intraocular concentration of VEGF-A is measured using multiplex immunoassay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of the other cytokines from 8 weeks to 20 weeks</measure>
    <time_frame>8 weeks and 20 weeks</time_frame>
    <description>Intraocular concentration of the other cytokines including angiopoietin-1, interleukin-10 (IL-10), platelet-derived growth factor (PDGF) and placental growth factor (PlGF) is measured using multiplex immunoassay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of cytokines from baseline to 8 weeks</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between time to recurrence and cytokine concentration at baseline and 8 weeks.</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Time to recurrence is defined as number of weeks from 8 to recurrence. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between vision changes and cytokine concentration changes</measure>
    <time_frame>baseline and 24 weeks.</time_frame>
    <description>Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher score represents better functioning. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between CSMT and cytokine concentration</measure>
    <time_frame>baseline, 8 weeks and 20 weeks.</time_frame>
    <description>CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as increase of en exudative sign. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between choroidal thickness and cytokine concentration</measure>
    <time_frame>baseline, 8 weeks and 20 weeks.</time_frame>
    <description>Choroidal thickness is thickness of the choroid measured at the foveal center using spectral-domain OCT. Increased choroidal thickness was reported to be related to poor response to anti-VEGF treatment. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between area of new vessels and cytokine concentration</measure>
    <time_frame>baseline</time_frame>
    <description>Area of new vessels is measured in indocyanine green angiography (ICGA) obtained at baseline. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between polyp closure and cytokine concentration changes</measure>
    <time_frame>baseline and 8 weeks</time_frame>
    <description>Polyp closure is defined as disappearance of polypoidal terminal in new vessels assessed in ICGA at 8 weeks. The difference of cytokine concentration is assessed between the closed group and un-closed group using non-parametric analysis, or Mann-Whitney U test.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Exudative Age-related Macular Degeneration</condition>
  <condition>Polypoidal Choroidal Vasculopathy</condition>
  <arm_group>
    <arm_group_label>pro-re-nata</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ranibizumab 0.5mg is injected in to the vitreous cavity. An injection is given every 4 weeks three times, and then the patient will be followed up every 4 weeks. An addition injection is given as needed. Recurrence is defined as increase of exudative changes, or increase of 10% or more in central subfield macular thickness (CSMT) measured using optical coherence tomography. Aqueous humor is sampled from the anterior chamber before injection at baseline, 8 weeks and 20 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ranibizumab</intervention_name>
    <description>Ranibizumab 0.5mg is injected into the vitreous cavity through the pars plana using 30 gauge (or narrower) needle-attached syringe.</description>
    <arm_group_label>pro-re-nata</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Submacular PCV diagnosed based on branching neovascular networks having polypoidal&#xD;
             dilatation in ICGA.&#xD;
&#xD;
          2. Presence of exudative changes involving the fovea in OCT&#xD;
&#xD;
          3. Decreased visual acuity to 20/320 - 20/40 to be primarily the results of PCV in the&#xD;
             study eye.&#xD;
&#xD;
          4. Willing and able to comply with clinic visits and study-related procedures, and&#xD;
             provide a signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Extramacular PCV.&#xD;
&#xD;
          2. Presence of pathologic changes blocking 50% or more area of the lesion in angiography.&#xD;
&#xD;
          3. Any anti-VEGF treatment in the study eye within 180 days of day 1.&#xD;
&#xD;
          4. Previous photodynamic therapy in the study eye.&#xD;
&#xD;
          5. History of intraocular surgery except uncomplicated cataract surgery performed before&#xD;
             90 days or more from day 1.&#xD;
&#xD;
          6. Presence of exudative ARMD requiring anti-VEGF treatment in the other eye.&#xD;
&#xD;
          7. Presence of other ocular disease that may compromise visual acuity in the study eye.&#xD;
&#xD;
          8. Uncontrolled systemic disease.&#xD;
&#xD;
          9. Active intraocular or periocular infection.&#xD;
&#xD;
         10. Active intraocular inflammation.&#xD;
&#xD;
         11. Hypersensitivity to ranibizumab or excipients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ji Eun Lee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pusan National University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pusan National University Yangsan Hospital</name>
      <address>
        <city>Yangsan</city>
        <state>Gyeongsangnam-do</state>
        <zip>50612</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Cha DM, Woo SJ, Kim HJ, Lee C, Park KH. Comparative analysis of aqueous humor cytokine levels between patients with exudative age-related macular degeneration and normal controls. Invest Ophthalmol Vis Sci. 2013 Oct 25;54(10):7038-44. doi: 10.1167/iovs.13-12730.</citation>
    <PMID>24106111</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>Hu J, Leng X, Hu Y, Atik A, Song X, Li Z, Liu Y, Lu L. The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy. PLoS One. 2016 Jan 22;11(1):e0147346. doi: 10.1371/journal.pone.0147346. eCollection 2016.</citation>
    <PMID>26799405</PMID>
  </reference>
  <reference>
    <citation>Sakurada Y, Nakamura Y, Yoneyama S, Mabuchi F, Gotoh T, Tateno Y, Sugiyama A, Kubota T, Iijima H. Aqueous humor cytokine levels in patients with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Ophthalmic Res. 2015;53(1):2-7. doi: 10.1159/000365487. Epub 2014 Nov 29.</citation>
    <PMID>25472810</PMID>
  </reference>
  <reference>
    <citation>Tong JP, Chan WM, Liu DT, Lai TY, Choy KW, Pang CP, Lam DS. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol. 2006 Mar;141(3):456-62. doi: 10.1016/j.ajo.2005.10.012.</citation>
    <PMID>16490490</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>November 22, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>October 8, 2019</last_update_submitted>
  <last_update_submitted_qc>October 8, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 10, 2019</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>Macular Degeneration</mesh_term>
    <mesh_term>Polypoidal Choroidal Vasculopathy</mesh_term>
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>
  <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/NCT02976194
org study id: 2016-0186
nct id: NCT02976194
lead sponsor: 
collaborator: 
has dmc: No
Changes of intraocular cytokines including vascular endothelial growth factor (VEGF) will be
      measured in recurrence of polypoidal choroidal vasculopathy (PCV) during treatment of
      ranibizumab.
PCV is regarded as a subtype of age-related macular degeneration (ARMD), but has several
      different features such as polypoidal terminal of new vessels, and relative resistance to
      anti-VEGF treatment. Other cytokines then VEGF are thought to be associated with development
      and progression of the disease. The aim of the this study is to investigate intraocular
      cytokines related to recurrence of polypoidal choroidal vasculopathy. Aqueous humor will be
      sampled from the anterior chamber at baseline, after loading injections of ranibizumab and at
      recurrence. The concentration of various cytokines will be measured in the aqueous humor.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Changes of VEGF-A from 8 weeks to 20 weeks
time frame: 8 weeks and 20 weeks
description: Intraocular concentration of VEGF-A is measured using multiplex immunoassay.
measure: Changes of the other cytokines from 8 weeks to 20 weeks
time frame: 8 weeks and 20 weeks
description: Intraocular concentration of the other cytokines including angiopoietin-1, interleukin-10 (IL-10), platelet-derived growth factor (PDGF) and placental growth factor (PlGF) is measured using multiplex immunoassay.
measure: Changes of cytokines from baseline to 8 weeks
time frame: baseline and 8 weeks
description: Intraocular concentration of cytokines including VEGF, angiopoietin-1, IL-10, PDGF and PlGF is measured using multiplex immunoassay.
measure: Correlation between time to recurrence and cytokine concentration at baseline and 8 weeks.
time frame: baseline and 8 weeks
description: Time to recurrence is defined as number of weeks from 8 to recurrence. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
measure: Correlation between vision changes and cytokine concentration changes
time frame: baseline and 24 weeks.
description: Visual acuity is assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The ETDRS chart includes 100 letters as the maximum possible score, and 0 letters read as the minimum possible score. Visual acuity of 85 letters is equivalent to 20/20. Higher score represents better functioning. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
measure: Correlation between CSMT and cytokine concentration
time frame: baseline, 8 weeks and 20 weeks.
description: CSMT is central 1mm thickness of the macula measured using spectral-domain optical coherence tomography (OCT). Normal thickness is around 250μm. Increased CSMT is regarded as increase of en exudative sign. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
measure: Correlation between choroidal thickness and cytokine concentration
time frame: baseline, 8 weeks and 20 weeks.
description: Choroidal thickness is thickness of the choroid measured at the foveal center using spectral-domain OCT. Increased choroidal thickness was reported to be related to poor response to anti-VEGF treatment. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
measure: Correlation between area of new vessels and cytokine concentration
time frame: baseline
description: Area of new vessels is measured in indocyanine green angiography (ICGA) obtained at baseline. The correlation is assessed using non-parametric analysis, or Spearman's ranked correlation.
measure: Correlation between polyp closure and cytokine concentration changes
time frame: baseline and 8 weeks
description: Polyp closure is defined as disappearance of polypoidal terminal in new vessels assessed in ICGA at 8 weeks. The difference of cytokine concentration is assessed between the closed group and un-closed group using non-parametric analysis, or Mann-Whitney U test.
arm group label: pro-re-nata
arm group type: Experimental
description: Ranibizumab 0.5mg is injected in to the vitreous cavity. An injection is given every 4 weeks three times, and then the patient will be followed up every 4 weeks. An addition injection is given as needed. Recurrence is defined as increase of exudative changes, or increase of 10% or more in central subfield macular thickness (CSMT) measured using optical coherence tomography. Aqueous humor is sampled from the anterior chamber before injection at baseline, 8 weeks and 20 weeks.
intervention type: Drug
intervention name: ranibizumab
description: Ranibizumab 0.5mg is injected into the vitreous cavity through the pars plana using 30 gauge (or narrower) needle-attached syringe.
arm group label: pro-re-nata
other name: Lucentis
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Ji Eun Lee, MD, PhD
role: Principal Investigator
affiliation: Pusan National University Hospital
facility: 
facility: 
country: Korea, Republic of
citation: Cha DM, Woo SJ, Kim HJ, Lee C, Park KH. Comparative analysis of aqueous humor cytokine levels between patients with exudative age-related macular degeneration and normal controls. Invest Ophthalmol Vis Sci. 2013 Oct 25;54(10):7038-44. doi: 10.1167/iovs.13-12730.
PMID: 24106111
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: Hu J, Leng X, Hu Y, Atik A, Song X, Li Z, Liu Y, Lu L. The Features of Inflammation Factors Concentrations in Aqueous Humor of Polypoidal Choroidal Vasculopathy. PLoS One. 2016 Jan 22;11(1):e0147346. doi: 10.1371/journal.pone.0147346. eCollection 2016.
PMID: 26799405
citation: Sakurada Y, Nakamura Y, Yoneyama S, Mabuchi F, Gotoh T, Tateno Y, Sugiyama A, Kubota T, Iijima H. Aqueous humor cytokine levels in patients with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. Ophthalmic Res. 2015;53(1):2-7. doi: 10.1159/000365487. Epub 2014 Nov 29.
PMID: 25472810
citation: Tong JP, Chan WM, Liu DT, Lai TY, Choy KW, Pang CP, Lam DS. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol. 2006 Mar;141(3):456-62. doi: 10.1016/j.ajo.2005.10.012.
PMID: 16490490
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Polypoidal Choroidal Vasculopathy
mesh term: Vascular Diseases
mesh term: Recurrence
mesh term: Ranibizumab
sharing ipd: No