- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02148016
Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Ying Lin, MD, PhD
- Email: lylytulip@126.com
Study Locations
-
-
-
Guangzhou, China
- Recruiting
- Zhongshan Ophthalmic Center, Sun Yat-sen University
-
Principal Investigator:
- Yizhi Liu, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LSCs and amniotic membrane (Modified Technique)
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. |
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. |
Active Comparator: Amniotic membrane only (Traditional Technique)
Amniotic membrane alone will be used to cover the corneal surface, after removal of scar tissue from a chemical injury or pterygium.
|
Amniotic membrane alone will be used to cover the corneal surface, after removal of scar tissue from a chemical injury or pterygium.
|
Experimental: PRK, LSCs, and amniotic membrane (Modified Technique)
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. |
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. |
Active Comparator: PRK only (Traditional Technique)
PRK alone will be performed.
|
PRK alone will be performed.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Composite measure of visual function in eyes treated for corneal ocular surface disease.
Time Frame: up to 1 year
|
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)
Time Frame: up to 1 year
|
up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of transparency of the cornea
Time Frame: up to 1 year
|
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.
|
up to 1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Postoperative complications
Time Frame: up to 1 year
|
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.
|
up to 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Yizhi Liu, MD, PhD, Zhongshan Ophthalmic Center, Sun Yat-sen University
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Eye Diseases
- Conjunctival Diseases
- Refractive Errors
- Myopia
- Pterygium
- Hyperopia
- Corneal Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Anti-Asthmatic Agents
- Respiratory System Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Anti-Infective Agents, Urinary
- Renal Agents
- Betamethasone
- Levofloxacin
- Ofloxacin
Other Study ID Numbers
- 2013SKL005
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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