Limbal Stem Cell DeficiencyPhase 2MLECNCT02318485
Limbal Epithelial Stem Cell Transplantation: a Phase II Multicenter Trial
A Phase 2 study testing Limbal epithelial stem cell graft in people with Limbal Stem Cell Deficiency, run by University Hospital, Antwerp at 3 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Limbal Stem Cell Deficiency
- What is being tested?
- Limbal epithelial stem cell graft
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesBelgium
- Study dates
- Apr 2015to 22 Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
Belgium3 sites
University Hospital Brussels
Brussels, 1090
Antwerp University Hospital
Edegem, Antwerp, 2650
University Hospital, Ghent
Ghent, 9000
About this study
Official title: Translational Stem Cell Research in Ophthalmology - Regenerating the Anterior Cornea Through Standardized Transplantation of Limbal Epithelial Stem Cells: a Phase II Multicenter Trial
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.
Read the detailed description
This project aims to conduct a multicenter, single-arm phase II study, in which we will assess the safety and efficacy of transplanting standardized, non-xenogenic limbal stem cell grafts for patients with LSCD. The Good Manufacturing Practice (GMP) clean room facilities at the Centre for Cell Therapy and Regenerative Medicine (CCRG, UZA) will conduct tissue engineering, while the Departments of Ophthalmology at the University Hospitals in Antwerp (UZA), Brussels (UZB) and Gent (UZG) will enrol patients, perform pre-operative tests, harvest the limbal biopsies, perform the auto- or allogenic graft transplantation and follow-up. Based on the past experience from our phase I/II mono-centre human clinical trial, we have been able to document the safety and feasibility of the transplantation. 12/18 patients (2/3 allogenic and 10/15 autologous) have shown decrease in corneal vascularization, complete epithelialization and incorporation of the graft into the anterior cornea post limbal stem cell transplantation. However our current results are limited with respect to the sample size, feasibility of allogenic transplantation (only 3 cases), long term follow-up (mean of 22 months, range 4-43 months) and disease monitoring strategies. Longer patient follow-up to determine long term success (especially following subsequent corneal transplants) and inclusion of a larger allogenic patient population need to be addressed before this treatment can be translated to the clinics and recognized by the RIZIV as a reimbursable cell therapy.
It is pertinent to say that this cell based therapy has the potential to provide this orphan pathology with an effective treatment option. The Flemish society will benefit from this project by improved rehabilitation of patients suffering from corneal blindness due to LSCD. By providing this treatment option we can offer a ray of hope to patients that would formerly have to learn to live with their disability. By restoring vision for these patients it is possible to reintegrate them into society as socially accepted individuals. Even a small degree of visual rehabilitation can make all the difference. For example, a slight increase in visual acuity can restore a person's ability to drive rather than having them rely exclusively on public transportation. More independence and a better quality of life are the main objectives that we are striving to achieve as the major outcome of this project.
- Conditions
- Limbal Stem Cell Deficiency
- Being tested
- Limbal epithelial stem cell graft
- Medical subject headings
- Limbal Stem Cell Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Limbal epithelial stem cell graftBiological
Also called limbo-amnion composite graft, Limbal stem cell graft
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Limbal epithelial stem cell graft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual acuity
using Log MAR scale
Measured: one year
presence of persistent epithelial defects
using Fluorescein drops and cobalt blue filter photography at the slit lamp
Measured: 3 months post surgery
presence of corneal conjunctivalization
slit lamp photography and in vivo confocal microscopy
Measured: one year
change in corneal vascularization
slit lamp photography
Measured: one year
Eye pain
using visual pain scale
Measured: one year
photophobia
using a 4 point scale
Measured: one year
Rejection
Increased neovascularization, epithelial defects and a drop in visual acuity Redness Pain Irritation slit lamp examination
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startApr 2015
- Primary completionJan 2023
- Study completion22 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Limbal Stem Cell DeficiencyStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Universitair Ziekenhuis Brussel, University Hospital, Ghent
- Responsible party
- Sponsor
- Investigators
- Sorcha Ni Dhubhghaill, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02318485
- Sponsor's protocol ID
- CCRG13-003
- Acronym
- MLEC
- Status last verified
- Jun 2024
- First submitted
- 2 Dec 2014
- Last updated
- 15 Jan 2025
- Results posted
- No
Publications
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.
PubMed 24589151
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translational Stem Cell Research in Ophthalmology - Regenerating the Anterior Cornea Through Standardized Transplantation of Limbal Epithelial Stem Cells: a Phase II Multicenter Trial
- ClinicalTrials.gov ID
- NCT02318485
- Acronym / sponsor ID
- MLEC / CCRG13-003
- Conditions
- Limbal Stem Cell Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Universitair Ziekenhuis Brussel, University Hospital, Ghent
- Study start
- Apr 2015
- Primary completion
- Jan 2023 (actual)
- Study completion
- 22 Apr 2024 (actual)
- First posted
- 17 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This project aims to conduct a multicenter, single-arm phase II study, in which we will assess the safety and efficacy of transplanting standardized, non-xenogenic limbal stem cell grafts for patients with LSCD. The Good Manufacturing Practice (GMP) clean room facilities at the Centre for Cell Therapy and Regenerative Medicine (CCRG, UZA) will conduct tissue engineering, while the Departments of Ophthalmology at the University Hospitals in Antwerp (UZA), Brussels (UZB) and Gent (UZG) will enrol patients, perform pre-operative tests, harvest the limbal biopsies, perform the auto- or allogenic graft transplantation and follow-up. Based on the past experience from our phase I/II mono-centre human clinical trial, we have been able to document the safety and feasibility of the transplantation. 12/18 patients (2/3 allogenic and 10/15 autologous) have shown decrease in corneal vascularization, complete epithelialization and incorporation of the graft into the anterior cornea post limbal stem cell transplantation. However our current results are limited with respect to the sample size, feasibility of allogenic transplantation (only 3 cases), long term follow-up (mean of 22 months, range 4-43 months) and disease monitoring strategies. Longer patient follow-up to determine long term success (especially following subsequent corneal transplants) and inclusion of a larger allogenic patient population need to be addressed before this treatment can be translated to the clinics and recognized by the RIZIV as a reimbursable cell therapy.
It is pertinent to say that this cell based therapy has the potential to provide this orphan pathology with an effective treatment option. The Flemish society will benefit from this project by improved rehabilitation of patients suffering from corneal blindness due to LSCD. By providing this treatment option we can offer a ray of hope to patients that would formerly have to learn to live with their disability. By restoring vision for these patients it is possible to reintegrate them into society as socially accepted individuals. Even a small degree of visual rehabilitation can make all the difference. For example, a slight increase in visual acuity can restore a person's ability to drive rather than having them rely exclusively on public transportation. More independence and a better quality of life are the main objectives that we are striving to achieve as the major outcome of this project.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant | Experimental | Biological: Limbal epithelial stem cell graftA limbal epithelial stem cell graft will be transplanted onto the limbal stem cell deficient eye after it has been debrided of fibrovascular pannus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Limbal epithelial stem cell graftAlso: limbo-amnion composite graft, Limbal stem cell graft | Biological | Transplant |
Primary outcome
Visual acuity
Time frame: one year
using Log MAR scale
presence of persistent epithelial defects
Time frame: 3 months post surgery
using Fluorescein drops and cobalt blue filter photography at the slit lamp
presence of corneal conjunctivalization
Time frame: one year
slit lamp photography and in vivo confocal microscopy
change in corneal vascularization
Time frame: one year
slit lamp photography
Eye pain
Time frame: one year
using visual pain scale
photophobia
Time frame: one year
using a 4 point scale
Rejection
Time frame: one year
Increased neovascularization, epithelial defects and a drop in visual acuity Redness Pain Irritation slit lamp examination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Results publication: PubMed 24589151Zakaria 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sorcha Ni Dhubhghaill principal investigator
University Hospital, Antwerp
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Limbal epithelial stem cell graft in people with Limbal Stem Cell Deficiency, run by University Hospital, Antwerp at 3 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual acuity (time frame: one year). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02318485, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2025.