Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation

NCT02148016 | Unknown Phase 1

• 1 other identifier: 2013SKL005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Corneal Disease; Pterygium; Myopia; Hyperopia

Keywords

Corneal disorders; Chemical injury; Pterygium; Refractive error; Myopia; Hyperopia; Cornea; Monocular; Transparent; Transplantation; Visual function

Outcome Measures

Primary Outcomes (2)

• 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.

  up to 1 year

• Composite measure of visual function in eyes after photo-refractive keratectomy (PRK)

  up to 1 year

Secondary Outcomes (1)

• Incidence of transparency of the cornea

  up to 1 year

Other Outcomes (1)

• Postoperative complications

  up to 1 year

Study Arms (4)

LSCs and amniotic membrane (Modified Technique)

EXPERIMENTAL

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.

Procedure: LSCs and amniotic membrane (Modified Technique); Drug: Levofloxacin; Drug: Betamethasone

Amniotic membrane only (Traditional Technique)

ACTIVE COMPARATOR

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

Procedure: Amniotic membrane only (Traditional Technique)

PRK, LSCs, and amniotic membrane (Modified Technique)

EXPERIMENTAL

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.

Procedure: PRK, LSCs, and amniotic membrane (Modified Technique); Drug: Levofloxacin; Drug: Betamethasone; Drug: Limbal stem cells (LSCs)

PRK only (Traditional Technique)

ACTIVE COMPARATOR

PRK alone will be performed.

Procedure: PRK only (Traditional Technique)

Interventions

LSCs and amniotic membrane (Modified Technique) PROCEDURE

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.

LSCs and amniotic membrane (Modified Technique)

Amniotic membrane only (Traditional Technique) PROCEDURE

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

Amniotic membrane only (Traditional Technique)

PRK, LSCs, and amniotic membrane (Modified Technique) PROCEDURE

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, LSCs, and amniotic membrane (Modified Technique)

PRK only (Traditional Technique) PROCEDURE

PRK alone will be performed.

PRK only (Traditional Technique)

Levofloxacin DRUG

LSCs and amniotic membrane (Modified Technique); PRK, LSCs, and amniotic membrane (Modified Technique)

Betamethasone DRUG

LSCs and amniotic membrane (Modified Technique); PRK, LSCs, and amniotic membrane (Modified Technique)

Limbal stem cells (LSCs) DRUG

PRK, LSCs, and amniotic membrane (Modified Technique)

Eligibility Criteria

• Age: 10 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Zhongshan Ophthalmic Center, Sun Yat-sen University

Guangzhou, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 24590515 BACKGROUND

• 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.

  PMID: 24589151 BACKGROUND

• 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.

  PMID: 24269851 BACKGROUND

• 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.

  PMID: 24705327 BACKGROUND

• 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.

  PMID: 23615271 BACKGROUND

• 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.

  PMID: 20573916 BACKGROUND

• 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.

  PMID: 25030175 BACKGROUND

MeSH Terms

Conditions

Corneal Diseases; Pterygium; Myopia; Hyperopia; Refractive Errors

Interventions

Levofloxacin; Betamethasone

Condition Hierarchy (Ancestors)

Eye Diseases; Conjunctival Diseases

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yizhi Liu, MD, PhD

  Zhongshan Ophthalmic Center, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Lin, MD, PhD

CONTACT

lylytulip@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: May 28, 2014
• Study Start: December 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 28, 2014

Record last verified: 2014-05

Locations

CN (1)