<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/NCT03295292</url>
  </required_header>
  <id_info>
    <org_study_id>LEC 07-17-068</org_study_id>
    <nct_id>NCT03295292</nct_id>
  </id_info>
  <brief_title>Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze</brief_title>
  <official_title>Pilot Clinical Trial to Assess the Safety of Limbus-derived Corneal Stem Cells in Prevention of Corneal Haze After Photo Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>L.V. Prasad Eye Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>L.V. Prasad Eye Institute</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a investigator-initiated pilot clinical trial to ascertain the safety and efficacy of&#xD;
      application of ex-vivo cultivated limbal stem cells in human eyes for treating Corneal Haze&#xD;
      after Photo-Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL).&#xD;
      Instead of using adjunctive medical therapy like application of MMC (Mitomycin), a technique&#xD;
      of cell delivery with fibrin sealant can be used. These cells are harvested from&#xD;
      therapeutically accepted and serologically tested cadaveric corneas. The isolated limbal&#xD;
      epithelial and mesenchymal or stromal cell suspension will then be cultured in CGMP&#xD;
      laboratories and be tested for sterlity. These cells have also been shown to be effective in&#xD;
      treating haze in laser refractive surgery in an animal model. Our initial experience of using&#xD;
      these cells in a previous clinical trial showed that they were effective in preventing&#xD;
      corneal haze in patients with burns and ulcers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this pilot clinical trial, patients undergoing Photo Therapeutic/Refractive Keratectomy&#xD;
      (PTK/ PRK) and Collagen Cross Linking (CXL), will be given human Limbus-derived Corneal Stem&#xD;
      cells to assess the safety of these cells. Cells will be cultivated in a cGMP laboratory&#xD;
      using standardized culture technique; from the limbal rims of cadaveric corneoscleral donor&#xD;
      tissues that are therapeutically accepted and serologically tested. Briefly the limbal tissue&#xD;
      will be cut up into small pieces and digested overnight using an enzyme (Collagenase L). The&#xD;
      cells obtained from the digest will be cultured on a petri-dish using 2% serum and growth&#xD;
      factors. A mixture of limbal epithelial cells and limbal stromal cells obtained from these&#xD;
      cultures will be used in surgical procedures in a ratio of 2:1, after all the sterility&#xD;
      checks. Mixed suspension of the limbal epithelial and the stromal cells at a concentration of&#xD;
      50000 cells/uL diluted in the thrombin component of fibrin sealant (TISEEL, Baxter) will be&#xD;
      applied. The primary outcome measure is safety of this treatment and the secondary outcome&#xD;
      measure is their efficacy that will be assessed at 1 month time points by (1) Clinical&#xD;
      photography using a standard method where multiple blinded observers will grade the&#xD;
      clinically apparent change in haze and (2) Objective quantification of the amount of light&#xD;
      scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>Phase 1</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, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maintenance of pre-operative best-spectacle corrected visual acuity</measure>
    <time_frame>1 month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy in reducing corneal light scatter using Scheimpflug imaging</measure>
    <time_frame>1 month</time_frame>
    <description>Efficacy in reducing corneal light scatter using Scheimpflug imaging at 1 month by:&#xD;
Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).&#xD;
• All routine clinical and imaging protocols performed for patients undergoing PTK/PRK and CXL will be diligently followed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Corneal Scars and Opacities</condition>
  <arm_group>
    <arm_group_label>Standard Surgery with Vehicle</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Surgery with Stem Cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL of a mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in the thrombin component of Fibrin Sealant (TISEEL, Baxter).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Stem cells</intervention_name>
    <description>Mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in fibrin sealant</description>
    <arm_group_label>Standard Surgery with Stem Cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Vehicle</intervention_name>
    <description>50uL of commercially available fibrin sealant (Baxter, TISEEL)</description>
    <arm_group_label>Standard Surgery with Stem Cells</arm_group_label>
    <arm_group_label>Standard Surgery with Vehicle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients between20 to 40 years of age&#xD;
&#xD;
          -  Meeting standard selection criteria for bilateral PTK/PRK or CXL&#xD;
&#xD;
          -  No systemic diseases&#xD;
&#xD;
          -  Eligible to give informed consent&#xD;
&#xD;
          -  No other ocular co-existing pathologies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Undergoing surgery in only one eye&#xD;
&#xD;
          -  Grossly asymmetric pathology&#xD;
&#xD;
          -  Refusal to give informed consent&#xD;
&#xD;
          -  Not agreeable or uncooperative for corneal imaging&#xD;
&#xD;
          -  Unlikely to come for follow-up for 1 month&#xD;
&#xD;
          -  International and out-station patients&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sayan Basu, MBBS MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>LV Prasad Eye Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vivek Singh, MSc PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LV Prasad Eye Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jagadesh C Reddy, MBBS MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LV Prasad Eye Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pratik Gogri, MBBS MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>LV Prasad Eye Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sayan Basu, MBBS MS</last_name>
    <phone>+9140 3061 2625</phone>
    <phone_ext>2625</phone_ext>
    <email>sayanbasu@lvpei.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pravin K Vaddavalli, MBBS MS</last_name>
    <phone>+91 40 3061 2626</phone>
    <phone_ext>2626</phone_ext>
    <email>pravin@lvpei.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>LV Prasad Eye Institute</name>
      <address>
        <city>Hyderabad</city>
        <state>Telangana</state>
        <zip>500034</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sayan Basu, MBBS MS</last_name>
      <phone>+9140 3061 2625</phone>
      <phone_ext>2625</phone_ext>
      <email>sayanbasu@lvpei.org</email>
    </contact>
    <contact_backup>
      <last_name>Vivek Singh, Msc PhD</last_name>
      <phone>+9140 3061 2286</phone>
      <phone_ext>2286</phone_ext>
      <email>viveksingh@lvpei.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <results_reference>
    <citation>Basu S, Hertsenberg AJ, Funderburgh ML, Burrow MK, Mann MM, Du Y, Lathrop KL, Syed-Picard FN, Adams SM, Birk DE, Funderburgh JL. Human limbal biopsy-derived stromal stem cells prevent corneal scarring. Sci Transl Med. 2014 Dec 10;6(266):266ra172. doi: 10.1126/scitranslmed.3009644.</citation>
    <PMID>25504883</PMID>
  </results_reference>
  <results_reference>
    <citation>Basu S, Damala M, Singh V. Limbal Stromal Stem Cell Therapy for Acute and Chronic Superficial Corneal Pathologies: Early Clinical Outcomes of The Funderburgh Technique. Investigative Ophthalmology &amp; Visual Science. 2017 Jun 23;58(8):3371-337</citation>
  </results_reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 27, 2017</study_first_posted>
  <last_update_submitted>February 25, 2019</last_update_submitted>
  <last_update_submitted_qc>February 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>L.V. Prasad Eye Institute</investigator_affiliation>
    <investigator_full_name>Vivek Singh</investigator_full_name>
    <investigator_title>Prinicipal Investigator</investigator_title>
  </responsible_party>
  <keyword>Phototherapeutic Keratectomy (PTK)</keyword>
  <keyword>photorefractive Keratectomy (PRK)</keyword>
  <keyword>Collagen Cross-linking (CXL)</keyword>
  <keyword>Stem Cell Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Corneal Injuries</mesh_term>
  </condition_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/NCT03295292
org study id: LEC 07-17-068
nct id: NCT03295292
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a investigator-initiated pilot clinical trial to ascertain the safety and efficacy of
      application of ex-vivo cultivated limbal stem cells in human eyes for treating Corneal Haze
      after Photo-Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL).
      Instead of using adjunctive medical therapy like application of MMC (Mitomycin), a technique
      of cell delivery with fibrin sealant can be used. These cells are harvested from
      therapeutically accepted and serologically tested cadaveric corneas. The isolated limbal
      epithelial and mesenchymal or stromal cell suspension will then be cultured in CGMP
      laboratories and be tested for sterlity. These cells have also been shown to be effective in
      treating haze in laser refractive surgery in an animal model. Our initial experience of using
      these cells in a previous clinical trial showed that they were effective in preventing
      corneal haze in patients with burns and ulcers.
In this pilot clinical trial, patients undergoing Photo Therapeutic/Refractive Keratectomy
      (PTK/ PRK) and Collagen Cross Linking (CXL), will be given human Limbus-derived Corneal Stem
      cells to assess the safety of these cells. Cells will be cultivated in a cGMP laboratory
      using standardized culture technique; from the limbal rims of cadaveric corneoscleral donor
      tissues that are therapeutically accepted and serologically tested. Briefly the limbal tissue
      will be cut up into small pieces and digested overnight using an enzyme (Collagenase L). The
      cells obtained from the digest will be cultured on a petri-dish using 2% serum and growth
      factors. A mixture of limbal epithelial cells and limbal stromal cells obtained from these
      cultures will be used in surgical procedures in a ratio of 2:1, after all the sterility
      checks. Mixed suspension of the limbal epithelial and the stromal cells at a concentration of
      50000 cells/uL diluted in the thrombin component of fibrin sealant (TISEEL, Baxter) will be
      applied. The primary outcome measure is safety of this treatment and the secondary outcome
      measure is their efficacy that will be assessed at 1 month time points by (1) Clinical
      photography using a standard method where multiple blinded observers will grade the
      clinically apparent change in haze and (2) Objective quantification of the amount of light
      scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Maintenance of pre-operative best-spectacle corrected visual acuity
time frame: 1 month
measure: Efficacy in reducing corneal light scatter using Scheimpflug imaging
time frame: 1 month
description: Efficacy in reducing corneal light scatter using Scheimpflug imaging at 1 month by:
Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).
• All routine clinical and imaging protocols performed for patients undergoing PTK/PRK and CXL will be diligently followed.
arm group label: Standard Surgery with Vehicle
arm group type: Sham Comparator
description: After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells.
arm group label: Standard Surgery with Stem Cells
arm group type: Experimental
description: After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL of a mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in the thrombin component of Fibrin Sealant (TISEEL, Baxter).
intervention type: Biological
intervention name: Stem cells
description: Mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in fibrin sealant
arm group label: Standard Surgery with Stem Cells
intervention type: Other
intervention name: Vehicle
description: 50uL of commercially available fibrin sealant (Baxter, TISEEL)
arm group label: Standard Surgery with Stem Cells
arm group label: Standard Surgery with Vehicle
criteria: 
gender: All
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: No
last name: Sayan Basu, MBBS MS
role: Principal Investigator
affiliation: LV Prasad Eye Institute
last name: Vivek Singh, MSc PhD
role: Principal Investigator
affiliation: LV Prasad Eye Institute
last name: Jagadesh C Reddy, MBBS MD
role: Principal Investigator
affiliation: LV Prasad Eye Institute
last name: Pratik Gogri, MBBS MS
role: Principal Investigator
affiliation: LV Prasad Eye Institute
last name: Sayan Basu, MBBS MS
phone: +9140 3061 2625
phone ext: 2625
email: sayanbasu@lvpei.org
last name: Pravin K Vaddavalli, MBBS MS
phone: +91 40 3061 2626
phone ext: 2626
email: pravin@lvpei.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: India
citation: Basu S, Hertsenberg AJ, Funderburgh ML, Burrow MK, Mann MM, Du Y, Lathrop KL, Syed-Picard FN, Adams SM, Birk DE, Funderburgh JL. Human limbal biopsy-derived stromal stem cells prevent corneal scarring. Sci Transl Med. 2014 Dec 10;6(266):266ra172. doi: 10.1126/scitranslmed.3009644.
PMID: 25504883
citation: Basu S, Damala M, Singh V. Limbal Stromal Stem Cell Therapy for Acute and Chronic Superficial Corneal Pathologies: Early Clinical Outcomes of The Funderburgh Technique. Investigative Ophthalmology & Visual Science. 2017 Jun 23;58(8):3371-337
responsible party type: Principal Investigator
investigator affiliation: L.V. Prasad Eye Institute
investigator full name: Vivek Singh
investigator title: Prinicipal Investigator
mesh term: Corneal Injuries
sharing ipd: No