<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/NCT04490902</url>
  </required_header>
  <id_info>
    <org_study_id>2020KYPJ111</org_study_id>
    <nct_id>NCT04490902</nct_id>
  </id_info>
  <brief_title>Clinical Study on the Treatment of Mixed Component Cornea for High Risk Keratoplasty</brief_title>
  <official_title>Suppression of Graft Rejection Using Mixed Component Cornea in the High-risk Keratoplasty，A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhongshan Ophthalmic Center, Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongshan Ophthalmic Center, Sun Yat-sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Because of the immunologically privileged nature of the cornea, the graft rejection rate is&#xD;
      less than 10% for low-risk keratoplasty. But when the cornea performed 2 or more quadrants of&#xD;
      corneal neovascularization after ocular trauma or infection, the graft rejection rate is more&#xD;
      than 65%, it is called high-risk keratoplasty.&#xD;
&#xD;
      This study will observe the graft survival of high-risk corneal transplantation using mixed&#xD;
      component cornea from different donors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ocular trauma or infection lead to corneal limbal stem cell deficiency and central corneal&#xD;
      opacification which could only be treated by central penetrating keratoplasty and limbal&#xD;
      transplantation, but the rejection rate is very high. In clinical, we found that limbal&#xD;
      transplantation combined with central penetrating keratoplasty from different donors can keep&#xD;
      the graft transparent for a long time, this result also be found in organ transplantation,&#xD;
      multiple donor organ transplantation could reduce rejection risk in liver and kidney&#xD;
      transplantation. Therefore, it is speculated that there are different MHC antigens from&#xD;
      different donors, which cause different reactions after transplantation. Because there are a&#xD;
      large number of Langerhans cells， abundant blood vessels and lymphatic in the limbal, so the&#xD;
      rejection occurs early and severely. Continuous and intense limbal rejection leads to the&#xD;
      depletion of recipient T cells, lead to the immune tolerance of another donor's central&#xD;
      corneal tissue. In this project, central penetrating keratoplasty and limbal transplantation&#xD;
      from different donors will be carried out and the graft survival of high-risk corneal&#xD;
      transplantation will be observed in clinical, to find a new method for high-risk corneal&#xD;
      transplant patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 18, 2020</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The rate of corneal graft rejection at 12 months</measure>
    <time_frame>12 months</time_frame>
    <description>The rejection index of corneal transplantation will be observed by slit lamp after surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The changes of best corrected visual acuity</measure>
    <time_frame>Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Best corrected visual acuity in different point will be compared with preoperative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of corneal thickness depth</measure>
    <time_frame>baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Corneal thickness depth will be measured by anterior segmental OCT and compared with preoperative</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reconstruction of corneal limbal</measure>
    <time_frame>baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Confocal microscopy will be used to define whether the structure of corneal limbal has reconstructed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial Cell Density</measure>
    <time_frame>baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Endothelial Cell Density will be measured by specular microscope to evaluate the loss of endothelial cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of presence of goblet cells containing conjunctival epithelium on the corneal surface by impression cytology</measure>
    <time_frame>baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Detects whether conjunctival epithelial and goblet cells have invaded the corneal surface by impression cytology, to observe the reconstruction of limbal function</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Intraocular pressure</measure>
    <time_frame>Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months</time_frame>
    <description>Intraocular pressure will be measured by non contact tonometer as safety index</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Corneal Transplantation</condition>
  <arm_group>
    <arm_group_label>Single graft corneal transplantation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Limbal transplantation combined with central penetrating keratoplasty from single donors.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dual graft corneal transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Limbal transplantation combined with central penetrating keratoplasty from different donors.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Limbal transplantation combined with central penetrating keratoplasty</intervention_name>
    <description>Limbal transplantation combined with central penetrating keratoplasty with single donor cornea</description>
    <arm_group_label>Single graft corneal transplantation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Limbal transplantation combined with central penetrating keratoplasty</intervention_name>
    <description>Limbal transplantation combined with central penetrating keratoplasty with mixed component cornea</description>
    <arm_group_label>Dual graft corneal transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Central corneal opacity involving full layer&#xD;
&#xD;
          -  Corneal neovascularization in two or more quadrants&#xD;
&#xD;
          -  Patients must be willing and able to return for scheduled follow-up examinations for&#xD;
             12 months after surgery&#xD;
&#xD;
          -  Ages：18 -70 Years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Central corneal opacity not involving the endothelial layer&#xD;
&#xD;
          -  Less than two quadrants of corneal neovascularization&#xD;
&#xD;
          -  History of Stevens-Johnson syndrome or Sjogren's syndrome&#xD;
&#xD;
          -  Severe eyelid and conjunctival scar&#xD;
&#xD;
          -  Loss of vision in contralateral eye&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ting Huang, MD, PHD</last_name>
    <phone>86-13552338050</phone>
    <email>qingerdong@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Zhongshan Ophthalmic Center, Sun Yat-Sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ling Jin</last_name>
      <phone>86-20-87334687</phone>
      <email>lingjin41@yahoo.com</email>
    </contact>
    <investigator>
      <last_name>Ting Huang, MD, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 29, 2020</study_first_posted>
  <last_update_submitted>February 22, 2022</last_update_submitted>
  <last_update_submitted_qc>February 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High-risk corneal transplantation</keyword>
  <keyword>Penetrating keratoplasty</keyword>
  <keyword>Limbal transplantation</keyword>
  <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/NCT04490902
org study id: 2020KYPJ111
nct id: NCT04490902
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Because of the immunologically privileged nature of the cornea, the graft rejection rate is
      less than 10% for low-risk keratoplasty. But when the cornea performed 2 or more quadrants of
      corneal neovascularization after ocular trauma or infection, the graft rejection rate is more
      than 65%, it is called high-risk keratoplasty.

      This study will observe the graft survival of high-risk corneal transplantation using mixed
      component cornea from different donors.
Ocular trauma or infection lead to corneal limbal stem cell deficiency and central corneal
      opacification which could only be treated by central penetrating keratoplasty and limbal
      transplantation, but the rejection rate is very high. In clinical, we found that limbal
      transplantation combined with central penetrating keratoplasty from different donors can keep
      the graft transparent for a long time, this result also be found in organ transplantation,
      multiple donor organ transplantation could reduce rejection risk in liver and kidney
      transplantation. Therefore, it is speculated that there are different MHC antigens from
      different donors, which cause different reactions after transplantation. Because there are a
      large number of Langerhans cells， abundant blood vessels and lymphatic in the limbal, so the
      rejection occurs early and severely. Continuous and intense limbal rejection leads to the
      depletion of recipient T cells, lead to the immune tolerance of another donor's central
      corneal tissue. In this project, central penetrating keratoplasty and limbal transplantation
      from different donors will be carried out and the graft survival of high-risk corneal
      transplantation will be observed in clinical, to find a new method for high-risk corneal
      transplant patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: The rate of corneal graft rejection at 12 months
time frame: 12 months
description: The rejection index of corneal transplantation will be observed by slit lamp after surgery
measure: The changes of best corrected visual acuity
time frame: Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months
description: Best corrected visual acuity in different point will be compared with preoperative
measure: The changes of corneal thickness depth
time frame: baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
description: Corneal thickness depth will be measured by anterior segmental OCT and compared with preoperative
measure: Reconstruction of corneal limbal
time frame: baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
description: Confocal microscopy will be used to define whether the structure of corneal limbal has reconstructed
measure: Endothelial Cell Density
time frame: baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
description: Endothelial Cell Density will be measured by specular microscope to evaluate the loss of endothelial cells
measure: The rate of presence of goblet cells containing conjunctival epithelium on the corneal surface by impression cytology
time frame: baseline (Before surgery), 1 week, 1 month, 3 months, 6 months, 12 months
description: Detects whether conjunctival epithelial and goblet cells have invaded the corneal surface by impression cytology, to observe the reconstruction of limbal function
measure: Intraocular pressure
time frame: Before surgery, 1 week, 1 month, 3 months, 6 months, 12 months
description: Intraocular pressure will be measured by non contact tonometer as safety index
arm group label: Single graft corneal transplantation
arm group type: Active Comparator
description: Limbal transplantation combined with central penetrating keratoplasty from single donors.
arm group label: Dual graft corneal transplantation
arm group type: Experimental
description: Limbal transplantation combined with central penetrating keratoplasty from different donors.
intervention type: Procedure
intervention name: Limbal transplantation combined with central penetrating keratoplasty
description: Limbal transplantation combined with central penetrating keratoplasty with single donor cornea
arm group label: Single graft corneal transplantation
intervention type: Procedure
intervention name: Limbal transplantation combined with central penetrating keratoplasty
description: Limbal transplantation combined with central penetrating keratoplasty with mixed component cornea
arm group label: Dual graft corneal transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ting Huang, MD, PHD
phone: 86-13552338050
email: qingerdong@126.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
sharing ipd: No