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Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation

Primary Purpose

Corneal Disease, Pterygium, Myopia

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LSCs and amniotic membrane (Modified Technique)
Amniotic membrane only (Traditional Technique)
PRK, LSCs, and amniotic membrane (Modified Technique)
PRK only (Traditional Technique)
Levofloxacin
Betamethasone
Limbal stem cells (LSCs)
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corneal Disease focused on measuring Corneal disorders, Chemical injury, Pterygium, Refractive error, Myopia, Hyperopia, Cornea, Monocular, Transparent, Transplantation, Visual function

Eligibility Criteria

10 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Monocular corneal chemical injury or pterygium, or refractive error greater than +/- 2D
  • Informed consent signed by patient or legal guardian

Exclusion Criteria:

  • Patients with a history of corneal perforation or surgery
  • Patients with other eye diseases
  • Patients with a history of severe cardiovascular, liver, kidney, endocrine, and hematopoietic disease, diabetes, or immune deficiency disorders
  • Pregnant or lactating women
  • Patients who are participating in other clinical trials
  • Patients with a history of mental illness who are unable to give informed consent or follow up according to the study protocol.

Sites / Locations

  • Zhongshan Ophthalmic Center, Sun Yat-sen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

LSCs and amniotic membrane (Modified Technique)

Amniotic membrane only (Traditional Technique)

PRK, LSCs, and amniotic membrane (Modified Technique)

PRK only (Traditional Technique)

Arm Description

Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following removal of scar tissue due to chemical injury or pterygium. The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.

Amniotic membrane alone will be used to cover the corneal surface, after removal of scar tissue from a chemical injury or pterygium.

Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following photo-refractive keratectomy (PRK). The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.

PRK alone will be performed.

Outcomes

Primary Outcome Measures

Composite measure of visual function in eyes treated for corneal ocular surface disease.
Slitlamp examination, in addition to measurement of visual acuity and intraocular pressure.
Composite measure of visual function in eyes after photo-refractive keratectomy (PRK)

Secondary Outcome Measures

Incidence of transparency of the cornea
Anterior segment photography and OCT as well as pentacam photography will be performed post treatment on day 1, week 1, week 2, month 1, month 3, month 6, and year 1, in order to assess transparency and curvature of the cornea.

Full Information

First Posted
May 19, 2014
Last Updated
May 27, 2014
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02148016
Brief Title
Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation
Official Title
Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Unknown status
Study Start Date
December 2012 (undefined)
Primary Completion Date
June 2014 (Anticipated)
Study Completion Date
September 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Corneal disease is a leading cause of blindness in the world. A shortage of corneal donor tissue has prevented many patients from regaining vision. Additionally, refractive error such as myopia is a major cause of impaired visual function worldwide. Although refractive error is correctable by procedures that modify the refractive power of the cornea, these procedures often weaken corneal integrity and have risk of complications. This study aims to evaluate the safety and efficacy of corneal surface epithelium repair and regeneration in the treatment of corneal surface diseases and refractive error using autologous limbal stem cell transplantation.
Detailed Description
The corneal surface is comprised of a unique type of non-keratinized epithelial cell. These cells are arranged in an orderly fashion, which is essential for vision by maintaining the transparency of the visual axis. Chemical injury and pterygia may damage the limbus, the zone between the cornea and the bulbar conjunctiva, and cause limbal stem cell (LSC) deficiency. They represent major treatable causes of vision loss worldwide. A shortage of corneal donor tissue prevents many patients from regaining vision, necessitating new treatment strategies to circumvent this limitation. Transplantation of stem cells represents an appealing therapeutic strategy in regenerative medicine, and the use of endogenous stem cells provides a possible solution to the problem of immune rejection. Currently, LASIK (laser-assisted in situ keratomileusis) is the most commonly performed laser vision correction procedure in the world (over 10 million surgeries each year); however, it has a major disadvantage in that it weakens corneal integrity and structure and predisposes to complications such as keratectasia or keratoconus (bulging of the cornea) and vision loss. An alternative is photo-refractive keratectomy (PRK), which removes the corneal epithelium and anterior stroma while minimizing the incidence of keratectasia or keratoconus. The primary drawbacks of PRK are that it requires a longer recovery time (the corneal epithelium must regenerate from the patient's own LSCs) and may result in blurry vision and pain due to corneal pain nerve fiber exposure after removal of the epithelium. Coverage of exposed corneal stroma tissue immediately after surgery with LSC-derived corneal epithelial cells will solve this key bottleneck and make laser eye surgery safer and more comfortable for millions of people. It is known that corneal renewal and repair are mediated by stem cells in the limbus. Autologous LSC transplantation has been reported previously (Rama et al.). However, mouse feeder cells were required to expand LSCs in culture. We have successfully developed a feeder-free, chemically defined medium in which to expand LSCs. These expanded LSCs can repair and regenerate corneal surfaces (Ouyang et al., in press). Hypothesis: The trial will demonstrate whether a new technique, transplantation of LSCs expanded from limbal tissue of the uninjured eye, can improve the visual function of patients with unilateral corneal ocular surface disease. In addition, it will show whether there is more rapid recovery and improved visual outcomes following PRK if expanded LSCs are used to cover the cornea. The study will also compare the incidence of complications and characterize visual outcomes in patients treated with the new technique versus the control technique.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Disease, Pterygium, Myopia, Hyperopia
Keywords
Corneal disorders, Chemical injury, Pterygium, Refractive error, Myopia, Hyperopia, Cornea, Monocular, Transparent, Transplantation, Visual function

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LSCs and amniotic membrane (Modified Technique)
Arm Type
Experimental
Arm Description
Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following removal of scar tissue due to chemical injury or pterygium. The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.
Arm Title
Amniotic membrane only (Traditional Technique)
Arm Type
Active Comparator
Arm Description
Amniotic membrane alone will be used to cover the corneal surface, after removal of scar tissue from a chemical injury or pterygium.
Arm Title
PRK, LSCs, and amniotic membrane (Modified Technique)
Arm Type
Experimental
Arm Description
Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following photo-refractive keratectomy (PRK). The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.
Arm Title
PRK only (Traditional Technique)
Arm Type
Active Comparator
Arm Description
PRK alone will be performed.
Intervention Type
Procedure
Intervention Name(s)
LSCs and amniotic membrane (Modified Technique)
Intervention Description
Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following removal of scar tissue due to chemical injury or pterygium. The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.
Intervention Type
Procedure
Intervention Name(s)
Amniotic membrane only (Traditional Technique)
Intervention Description
Amniotic membrane alone will be used to cover the corneal surface, after removal of scar tissue from a chemical injury or pterygium.
Intervention Type
Procedure
Intervention Name(s)
PRK, LSCs, and amniotic membrane (Modified Technique)
Intervention Description
Limbal stem cells (LSCs) from the contralateral eye will be harvested and expanded in feeder-free, chemically defined media for one week on a collagen-coated contact lens. The LSCs on contact lens will be transplanted onto a corneal surface in vivo, following photo-refractive keratectomy (PRK). The contact lens will then be covered with amniotic membrane to secure it in place. The eye will be treated with antibiotics (levofloxacin) and steroids (betamethasone), and then patched.
Intervention Type
Procedure
Intervention Name(s)
PRK only (Traditional Technique)
Intervention Description
PRK alone will be performed.
Intervention Type
Drug
Intervention Name(s)
Levofloxacin
Intervention Type
Drug
Intervention Name(s)
Betamethasone
Intervention Type
Drug
Intervention Name(s)
Limbal stem cells (LSCs)
Primary Outcome Measure Information:
Title
Composite measure of visual function in eyes treated for corneal ocular surface disease.
Description
Slitlamp examination, in addition to measurement of visual acuity and intraocular pressure.
Time Frame
up to 1 year
Title
Composite measure of visual function in eyes after photo-refractive keratectomy (PRK)
Time Frame
up to 1 year
Secondary Outcome Measure Information:
Title
Incidence of transparency of the cornea
Description
Anterior segment photography and OCT as well as pentacam photography will be performed post treatment on day 1, week 1, week 2, month 1, month 3, month 6, and year 1, in order to assess transparency and curvature of the cornea.
Time Frame
up to 1 year
Other Pre-specified Outcome Measures:
Title
Postoperative complications
Description
Slitlamp examination, anterior segment photography, anterior segment OCT, pentacam photography, in addition to measurement of visual acuity and intraocular pressure, will be performed post treatment on day 1, week 1, week 2, month 1, month 3, month 6, and year 1, in order to assess for any postoperative complications.
Time Frame
up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Monocular corneal chemical injury or pterygium, or refractive error greater than +/- 2D Informed consent signed by patient or legal guardian Exclusion Criteria: Patients with a history of corneal perforation or surgery Patients with other eye diseases Patients with a history of severe cardiovascular, liver, kidney, endocrine, and hematopoietic disease, diabetes, or immune deficiency disorders Pregnant or lactating women Patients who are participating in other clinical trials Patients with a history of mental illness who are unable to give informed consent or follow up according to the study protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Lin, MD, PhD
Email
lylytulip@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yizhi Liu, MD, PhD
Organizational Affiliation
Zhongshan Ophthalmic Center, Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhongshan Ophthalmic Center, Sun Yat-sen University
City
Guangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yizhi Liu, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
24590515
Citation
Kolli S, Ahmad S, Mudhar HS, Meeny A, Lako M, Figueiredo FC. Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Stem Cells. 2014 Aug;32(8):2135-46. doi: 10.1002/stem.1694.
Results Reference
background
PubMed Identifier
24589151
Citation
Zakaria N, Possemiers T, Dhubhghaill SN, Leysen I, Rozema J, Koppen C, Timmermans JP, Berneman Z, Tassignon MJ. Results of a phase I/II clinical trial: standardized, non-xenogenic, cultivated limbal stem cell transplantation. J Transl Med. 2014 Mar 3;12:58. doi: 10.1186/1479-5876-12-58.
Results Reference
background
PubMed Identifier
24269851
Citation
Vazirani J, Basu S, Kenia H, Ali MH, Kacham S, Mariappan I, Sangwan V. Unilateral partial limbal stem cell deficiency: contralateral versus ipsilateral autologous cultivated limbal epithelial transplantation. Am J Ophthalmol. 2014 Mar;157(3):584-90.e1-2. doi: 10.1016/j.ajo.2013.11.011. Epub 2013 Nov 19.
Results Reference
background
PubMed Identifier
24705327
Citation
Wu Z, Zhou Q, Duan H, Wang X, Xiao J, Duan H, Li N, Li C, Wan P, Liu Y, Song Y, Zhou C, Huang Z, Wang Z. Reconstruction of auto-tissue-engineered lamellar cornea by dynamic culture for transplantation: a rabbit model. PLoS One. 2014 Apr 4;9(4):e93012. doi: 10.1371/journal.pone.0093012. eCollection 2014.
Results Reference
background
PubMed Identifier
23615271
Citation
Konomi K, Satake Y, Shimmura S, Tsubota K, Shimazaki J. Long-term results of amniotic membrane transplantation for partial limbal deficiency. Cornea. 2013 Aug;32(8):1110-5. doi: 10.1097/ICO.0b013e31828d06d2.
Results Reference
background
PubMed Identifier
20573916
Citation
Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 Jul 8;363(2):147-55. doi: 10.1056/NEJMoa0905955. Epub 2010 Jun 23.
Results Reference
background
PubMed Identifier
25030175
Citation
Ouyang H, Xue Y, Lin Y, Zhang X, Xi L, Patel S, Cai H, Luo J, Zhang M, Zhang M, Yang Y, Li G, Li H, Jiang W, Yeh E, Lin J, Pei M, Zhu J, Cao G, Zhang L, Yu B, Chen S, Fu XD, Liu Y, Zhang K. WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis. Nature. 2014 Jul 17;511(7509):358-61. doi: 10.1038/nature13465. Epub 2014 Jul 2.
Results Reference
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Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation

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