Limbal Epithelial Stem Cell Transplantation: a Phase II Multicenter Trial

NCT02318485 | Completed Phase 2

• 1 other identifier: CCRG13-003
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

This project aims to conduct a multicentre human clinical trial to effectively diagnose and treat limbal stem cell deficiency (LSCD) which can be caused by a number of different disease processes, all of which have a common denominator, i.e. a loss of the normal functioning epithelial stem cells of the cornea. A number of different diseases such as aniridia, steven johnson's syndrome, ocular cicatricial pemphigoid, bacterial keratitis, or chemical and thermal injuries to the cornea can lead to gradual loss of its functioning epithelial stem cells. This leads to vascularization of the cornea with surrounding conjunctival epithelium growing over it resulting in its scarring and opacification. These corneas, since vascular, no longer retain their immune privilege and prove extremely challenging to the ophthalmic surgeon. Grafting donor corneas which in normal circumstances (non vascular corneas) would give excellent results, exhibit high rates of rejection. This can be very frustrating for both the patient as well as the surgeon. Since there are a number of different contributing disease pathologies, our estimate is that there are approximately 100 patients per year in Belgium that suffer from some degree of LSCD. These patients are very often not correctly diagnosed since this is a relatively new disease first described in 1990 after the discovery of limbal epithelial stem cells in 1989. The low rates of diagnosis could potentially be increased by in vivo confocal scanning microscopy as a non invasive screening test to detect early signs of LSCD and therefore offer conservative treatment options. In the cases where total limbal stem cell deficiency has already developed, conventional corneal grafting is not suitable due to the high vascularity of the host bed. In this situation we propose transplanting standardized limbal epithelial stem cell grafts generated from the patient's own ocular stem cells (from the good eye, where available) or from HLA matched donors. Tiny 1 by 2mm superficial limbal (peripheral cornea) biopsy can be taken and the epithelial stem cells expanded in the laboratory on a biological substrate, until there is a graft measuring \>8mm in diameter generated in 2 a week period. This can then be transplanted onto the diseased eye after removal of scar tissue using a novel surgical technique we have developed.

Conditions

Limbal Stem Cell Deficiency

Outcome Measures

Primary Outcomes (7)

• Visual acuity

  using Log MAR scale

  one year

• presence of persistent epithelial defects

  using Fluorescein drops and cobalt blue filter photography at the slit lamp

  3 months post surgery

• presence of corneal conjunctivalization

  slit lamp photography and in vivo confocal microscopy

  one year

• change in corneal vascularization

  slit lamp photography

  one year

• Eye pain

  using visual pain scale

  one year

• photophobia

  using a 4 point scale

  one year

• Rejection

  Increased neovascularization, epithelial defects and a drop in visual acuity Redness Pain Irritation slit lamp examination

  one year

Study Arms (1)

Transplant

EXPERIMENTAL

A limbal epithelial stem cell graft will be transplanted onto the limbal stem cell deficient eye after it has been debrided of fibrovascular pannus

Biological: Limbal epithelial stem cell graft

Interventions

Limbal epithelial stem cell graft BIOLOGICAL

Also known as: limbo-amnion composite graft, Limbal stem cell graft

Transplant

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years
• Voluntary written informed consent
• Patients suffering from LSCD IIa and IIb. Those suffering from IIc may be included once inflammation has subsided and cornea can be staged as IIb.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation. Negative serum or urine β-HCG pregnancy test at screening.

You may not qualify if:

• Subjects who are pregnant or lactating
• Subjects who have sensitivity to drugs that provide local anesthesia
• Subjects suffering from active infection of the external eye
• Medical conditions that prohibit the use of systemic immunosuppression (in cases of allogenic transplantation)

Sponsors & Collaborators

• University Hospital, Antwerp: lead
• Universitair Ziekenhuis Brussel: collaborator
• University Hospital, Ghent: collaborator

Study Sites (3)

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

Location

University Hospital Brussels

Brussels, 1090, Belgium

Location

University Hospital, Ghent

Ghent, 9000, Belgium

Location

Related Publications (1)

• 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 RESULT

MeSH Terms

Conditions

Limbal Stem Cell Deficiency

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Study Officials

• Sorcha Ni Dhubhghaill

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 17, 2014
• Study Start: April 1, 2015
• Primary Completion: January 1, 2023
• Study Completion: April 22, 2024
• Last Updated: January 15, 2025

Record last verified: 2024-06

Locations

BE (3)