<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/NCT02202642</url>
  </required_header>
  <id_info>
    <org_study_id>201007032D</org_study_id>
    <nct_id>NCT02202642</nct_id>
  </id_info>
  <brief_title>The Improvement of Limbal Epithelial Culture Technique by Using Collagenase to Isolate Limbal Stem Cells</brief_title>
  <official_title>The Improvement of Limbal Epithelial Culture Technique for the Treatment of Unilateral Limbal Insufficiency by Using Collagenase to Isolate Limbal Stem Cells</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion&#xD;
      of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell&#xD;
      insufficiency based on the concept of &quot;limbal stem cells need special cell-cell contact and&#xD;
      cell-extracellular matrix interaction to support their survival&quot;.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients suffering from unilateral limbal stem cell insufficiency and understand the benefits&#xD;
      and risk factors of the operation will be enrolled in this clinical trial. Two weeks before&#xD;
      transplantation, the investigators first take 1-2 mm2 of limbal tissues from the healthy eye,&#xD;
      digest the tissue with collagenase, and get an epithelial cell cluster. The cell cluster will&#xD;
      be cultured on amniotic membrane with SHEM medium which contains Dulbecco's modified Eagle's&#xD;
      medium/F12 (1:1), 5% dimethyl sulfoxide, 10 ng/ml human epidermal growth factor, 5μg/ml&#xD;
      insulin, 0.5 μg/ml hydrocortisone, 1 nM cholera toxin, 50μg/ml gentamicin, 1.25μg/ml&#xD;
      amphotericin B. Seven to ten days later after successful culture, transplantation will be&#xD;
      performed after the cells reaches 1.5-2 cm2 compact confluent epithelial sheets without&#xD;
      evidence of contamination. During the operation, lamellar keratectomy will be performed to&#xD;
      remove the abnormal corneal neovascularization and scar tissue. The cultivated epithelial&#xD;
      sheets will be transplanted to denuded corneal surface with fibrin glue and suture technique.&#xD;
      The patients are planed to be admitted for 2 weeks. After discharge, follow up of the&#xD;
      patients will be performed on one week, two week, one month, two months, three months, six&#xD;
      months and one year later. Pictures of external eyes will be taken and the extent of corneal&#xD;
      epithelium regeneration, visual acuity, and complications will be recorded during follow-up&#xD;
      visits. The investigators plan to collect 10 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2012</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment.</measure>
    <time_frame>12 months</time_frame>
    <description>Nine to twelve days later after successful culture, transplantation will be performed after the cells diameter reaches 1.5-2.0 cm compact confluent epithelial sheets without evidence of contamination.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Alkaline Chemical Burn Of Cornea And Conjunctival Sac</condition>
  <condition>Acid Chemical Burn Of Cornea And Conjunctival Sac</condition>
  <condition>Benign Mucous Membrane Pemphigoid With Ocular Involvement</condition>
  <arm_group>
    <arm_group_label>limbal stem cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell insufficiency based on the concept of &quot;limbal stem cells need special cell-cell contact and cell-extracellular matrix interaction to support their survival&quot;</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>collagenase</intervention_name>
    <description>Cultured limbal stem cells transplantation</description>
    <arm_group_label>limbal stem cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: between 18-70 years old.&#xD;
&#xD;
          2. Lesion eye should have limbal insufficiency more than 180 degrees.&#xD;
&#xD;
          3. Lesion eye should have recurrent corneal erosions, corneal neovascularisation and poor&#xD;
             vision caused by limbal insufficiency.&#xD;
&#xD;
          4. The symptoms should be more than 1/2 year, and have no possibility of improvement by&#xD;
             medical treatment.&#xD;
&#xD;
          5. The patients will to received the operation and the long term post- operative&#xD;
             follow-up.&#xD;
&#xD;
          6. The patients are not infected by AIDS, hepatitis B/C , and willing to received the&#xD;
             associated examinations.&#xD;
&#xD;
          7. The patients does not plan to be pregnant from the day of cell culture and&#xD;
             transplantation for 1 year. They also agree to receive the pregnant test.&#xD;
&#xD;
          8. The condition of cell culture from the 1st to the clinical trial is successful.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Bilateral limbal insufficiency.&#xD;
&#xD;
          2. No recurrent corneal erosion, corneal neovascularisation or poor vision was found due&#xD;
             to limbal insufficiency. If corneal neovascularisation was found deeper than the&#xD;
             anterior 1/2 of corneal stroma, or corneal thickness was less than 200 um evaluated by&#xD;
             anterior segment OCT and ultrasound pachymetry, the patients should be excluded from&#xD;
             the operation criteria. If corneal thickness becomes thicker, the patients can be&#xD;
             enrolled for operation.&#xD;
&#xD;
          3. About corneal sedation, if the value checked by Cocet-Bonnet esthesiometer is less&#xD;
             than 5 mm, the patients should be excluded from operation.&#xD;
&#xD;
          4. The condition can be improved by medication, or resolve spontaneously.&#xD;
&#xD;
          5. Post-operative follow up is less than 1/2 year&#xD;
&#xD;
          6. The patient can't receive long term postoperative follow up&#xD;
&#xD;
          7. No light perception, or can be expected to have very poor prognosis&#xD;
&#xD;
          8. If the intraocular pressure was more than 21 mmHg under necessary glaucoma surgery and&#xD;
             anti-glaucoma medication, or optic disc cupping was more than 90%, or visual field was&#xD;
             found to have severe defects, the patients were excluded from the clinical trial.&#xD;
&#xD;
          9. Severe lagophthalmos or trichiasis, and does not received blepharoplasty.&#xD;
&#xD;
         10. Severe dry eye syndrome. Those patients with schirmer's test result less than 1 mm&#xD;
             should be excluded.&#xD;
&#xD;
         11. If the cells in the first part of the clinical trial can't be successfully cultivated,&#xD;
             the patients should be excluded. If the patients insisted to received further&#xD;
             treatment, they can be enrolled 3 months later.&#xD;
&#xD;
         12. Pregnancy&#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_official>
    <last_name>Wei Li Chen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei Li Chen, MD, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>5206</phone_ext>
    <email>chenweili@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>Wei-Li Chen</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>April 21, 2011</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>July 24, 2014</last_update_submitted>
  <last_update_submitted_qc>July 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 29, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Taiwan University Hospital</investigator_affiliation>
    <investigator_full_name>National Taiwan University Hospital</investigator_full_name>
    <investigator_title>Wei-Li Chen/Assistant Professor, National Taiwan University, Department of Ophthalmology.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Eye Burns</mesh_term>
    <mesh_term>Corneal Diseases</mesh_term>
    <mesh_term>Pemphigoid, Benign Mucous Membrane</mesh_term>
    <mesh_term>Pemphigoid, Bullous</mesh_term>
    <mesh_term>Burns</mesh_term>
    <mesh_term>Burns, Chemical</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/NCT02202642
org study id: 201007032D
nct id: NCT02202642
lead sponsor: 
has dmc: Yes
Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion
      of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell
      insufficiency based on the concept of "limbal stem cells need special cell-cell contact and
      cell-extracellular matrix interaction to support their survival".
Patients suffering from unilateral limbal stem cell insufficiency and understand the benefits
      and risk factors of the operation will be enrolled in this clinical trial. Two weeks before
      transplantation, the investigators first take 1-2 mm2 of limbal tissues from the healthy eye,
      digest the tissue with collagenase, and get an epithelial cell cluster. The cell cluster will
      be cultured on amniotic membrane with SHEM medium which contains Dulbecco's modified Eagle's
      medium/F12 (1:1), 5% dimethyl sulfoxide, 10 ng/ml human epidermal growth factor, 5μg/ml
      insulin, 0.5 μg/ml hydrocortisone, 1 nM cholera toxin, 50μg/ml gentamicin, 1.25μg/ml
      amphotericin B. Seven to ten days later after successful culture, transplantation will be
      performed after the cells reaches 1.5-2 cm2 compact confluent epithelial sheets without
      evidence of contamination. During the operation, lamellar keratectomy will be performed to
      remove the abnormal corneal neovascularization and scar tissue. The cultivated epithelial
      sheets will be transplanted to denuded corneal surface with fibrin glue and suture technique.
      The patients are planed to be admitted for 2 weeks. After discharge, follow up of the
      patients will be performed on one week, two week, one month, two months, three months, six
      months and one year later. Pictures of external eyes will be taken and the extent of corneal
      epithelium regeneration, visual acuity, and complications will be recorded during follow-up
      visits. The investigators plan to collect 10 patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment.
time frame: 12 months
description: Nine to twelve days later after successful culture, transplantation will be performed after the cells diameter reaches 1.5-2.0 cm compact confluent epithelial sheets without evidence of contamination.
arm group label: limbal stem cells
arm group type: Experimental
description: Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell insufficiency based on the concept of "limbal stem cells need special cell-cell contact and cell-extracellular matrix interaction to support their survival"
intervention type: Procedure
intervention name: collagenase
description: Cultured limbal stem cells transplantation
arm group label: limbal stem cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Wei Li Chen, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Wei Li Chen, MD, PhD
phone: 886-2-23123456
phone ext: 5206
email: chenweili@ntu.edu.tw
facility: 
status: Recruiting
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: National Taiwan University Hospital
investigator full name: National Taiwan University Hospital
investigator title: Wei-Li Chen/Assistant Professor, National Taiwan University, Department of Ophthalmology.
mesh term: Eye Burns
mesh term: Corneal Diseases
mesh term: Pemphigoid, Benign Mucous Membrane
mesh term: Pemphigoid, Bullous
mesh term: Burns
mesh term: Burns, Chemical