PterygiumPhase 3NCT00346450
Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface Transplantation
A Phase 3 study testing Cultivated conjunctival transplantation in people with Pterygium and Ocular Surface Disease, run by Singapore National Eye Centre at 1 site in Singapore.
Trial summary
To evaluate the use of cultivated conjunctival epithelial equivalents for the treatment of ocular diseases Read more about this study
- Who is it for?
- Ages 21 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Pterygium, Ocular Surface Disease, Stevens Johnson Syndrome
- What is being tested?
- Cultivated conjunctival transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 1 siteSingapore
- Study dates
- Oct 2001to Dec 2003
- Phase
- Phase 3
- 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 21 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with ocular surface disorders, e.g. primary pterygium, scheduled for elective surgical excision
- Indications for surgery will be the presence of ocular surface symptoms in the affected eye, loss of visual acuity from visual axis obscuration or irregular astigmatism, or cosmesis.
- Only one eye of a patient will be eligible for study entry.
- Patients who are adult males and females who are aged 21 or older, and are considered mentally sound
- Patients who are willing to undergo long-term follow-up, as outlined in this protocol
- Patients who have signed an informed consent form that has been approved by the SNEC Ethics Committee.
Who cannot join
- Patients less than 21 years of age
- Patients who are incapable, either by law or of mental state, of giving consent in their own right
- Patients who are either unable or unwilling to keep scheduled appointments and adhere to the other aspects of the protocol
- Patients who are pregnant or breastfeeding
- Patients with a history of drug allergy
- Patients who have received an investigational drug within 28 days preceding surgery
- Patients with intraocular pressure over 21 mmHg or history of ocular hypertension or glaucoma
- Patients who are documented to be steroid responders
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface
To evaluate the use of cultivated conjunctival epithelial equivalents for the treatment of ocular diseases
Read the detailed description
Ex-vivo autologous conjunctiva expansion on human amniotic membrane (HAM), followed by clinical transplantation surgery
Preparation of HAM. Human amniotic membrane (HAM) prepared for human use will be obtained from the Singapore Eye Bank. HAM will be rapidly thawed in a 37oC water bath, and washed with phosphate buffered saline. The amniotic epithelium will be removed using a combination of Dispase digestion and mechanical scraping. Complete removal of the amniotic epithelial cells will be confirmed by microscopy. The HAM is then placed on a culture plate, with the basement-membrane side up, and incubated with DMEM at 37oC in an atmosphere of 5% CO2 and 95% air overnight before use.
Ex-vivo expansion of conjunctival cells on HAM. A forniceal conjunctival biopsy will be performed in patients undergoing pterygium surgery. The tissue will be cultured on the HAM either as a cell suspension or as explants, with the methods described above. The media is changed every 2 days and the culture is maintained for 2-3 weeks. The cells will form a confluent sheet and begin to stratify and differentiate. The tissue will then be raised to an air-liquid interface to promote differentiation.
Histological analysis. The conjunctival epithelial cell sheets on the amniotic membrane will be examined by light microscopy. Samples of the tissue will be fixed and processed with the use of standard histological procedures and stained with H\&E and PAS reagents. Electron microscopic examination will be carried for the tissue. The sections will also be subjected to immunohistochemical analysis for cytokeratin markers.
Clinical Transplantation of cultivated conjunctival epithelial cells on HAM
Preparation of cultivated conjunctival cells on amniotic membrane Patients with various ocular surface disorders will be selected for the initial series of transplantations. All patients will undergo full counselling for informed consent for the procedures. A forniceal conjunctival biopsy will be performed on the contralateral healthy eye. PI will perform the transplantations of autologous conjunctival sheet grown on human amniotic membrane in these patients. The diseased area will be excised using the standard surgical technique. The defect will be covered with the sheet of cultured conjunctival cells on the HAM with the epithelial side up. The graft is secured to the adjacent conjunctiva with interrupted 8/0 vicryl sutures. A planotherapeutic bandage contact lens is placed to protect the tissue from lid trauma. Topical steroid and antibiotic eyedrops will be administered daily to reduce the ocular inflammation. Survival of conjunctiva on the amniotic membrane will be closely monitored and patients will be followed-up at 3 monthly intervals up to one year. During these visits, these patients will have anterior segment photographs taken and fluorescein staining to monitor the progress of healing.
Transplantations may also be carried out on selected patients with ocular surface disease, for example, ocular cicatricial pemphigoid, Stevens Johnson syndrome and alkali injury. For these severe conditions, this procedure may prove to be an important adjunct to other procedures, such as limbal stem cell transplantation. If the initial study is successful, a randomised clinical trial comparing this procedure with conventional conjunctival autografting and conventional amniotic membrane transplantation will be planned. Therefore if found to be successful, transplantation of cultured conjunctival cells on HAM may eventually be used as a primary procedure or as an adjunctive procedure for these visually debilitating conditions.
- Being tested
- Cultivated conjunctival transplantation
- Keywords
- Culture, Conjunctiva, transplantation, pterygium, ocular surface
- Medical subject headings
- Pterygium, Stevens-Johnson Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cultivated conjunctival transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Epithelialisation
Graft integrity
Resolution of inflammation
Visual acuity
Complications
Secondary outcomes (1)
Degree of scarring
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2006 (estimated)
- Study startOct 2001
- Study completionDec 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PterygiumStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore National Eye Centre
- Sponsor type
- Other government
- Collaborators
- International Stem Cell Forum, National Medical Research Council (NMRC), Singapore, Singapore Eye Research Institute
- Investigators
- Leonard P Ang, FRCS, Principal investigator, SNEC, NUSDonald T Tan, FRCS, Principal investigator, SNEC, SERI, NUS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00346450
- Sponsor's protocol ID
- R198/24/2000
- Status last verified
- Jan 2010
- First submitted
- 29 Jun 2006
- Last updated
- 13 Jan 2010
- Results posted
- No
Publications
Ang LP, Tan DT, Beuerman RW, Lavker RM. Development of a conjunctival epithelial equivalent with improved proliferative properties using a multistep serum-free culture system. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1789-95. doi: 10.1167/iovs.03-1361.
PubMed 15161841Ang LP, Tan DT, Phan TT, Li J, Beuerman R, Lavker RM. The in vitro and in vivo proliferative capacity of serum-free cultivated human conjunctival epithelial cells. Curr Eye Res. 2004 May;28(5):307-17. doi: 10.1076/ceyr.28.5.307.28677.
PubMed 15287367
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous ex Vivo Conjunctival Epithelial Cell Expansion for Ocular Surface
- ClinicalTrials.gov ID
- NCT00346450
- Acronym / sponsor ID
- R198/24/2000
- Keywords
- Culture, Conjunctiva, transplantation, pterygium, ocular surface
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Singapore National Eye CentreOther government
- Collaborators
- International Stem Cell Forum, National Medical Research Council (NMRC), Singapore, Singapore Eye Research Institute
- Study start
- Oct 2001
- Study completion
- Dec 2003 (actual)
- First posted
- 30 Jun 2006 (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.
To evaluate the use of cultivated conjunctival epithelial equivalents for the treatment of ocular diseases
Detailed description
Ex-vivo autologous conjunctiva expansion on human amniotic membrane (HAM), followed by clinical transplantation surgery
Preparation of HAM. Human amniotic membrane (HAM) prepared for human use will be obtained from the Singapore Eye Bank. HAM will be rapidly thawed in a 37oC water bath, and washed with phosphate buffered saline. The amniotic epithelium will be removed using a combination of Dispase digestion and mechanical scraping. Complete removal of the amniotic epithelial cells will be confirmed by microscopy. The HAM is then placed on a culture plate, with the basement-membrane side up, and incubated with DMEM at 37oC in an atmosphere of 5% CO2 and 95% air overnight before use.
Ex-vivo expansion of conjunctival cells on HAM. A forniceal conjunctival biopsy will be performed in patients undergoing pterygium surgery. The tissue will be cultured on the HAM either as a cell suspension or as explants, with the methods described above. The media is changed every 2 days and the culture is maintained for 2-3 weeks. The cells will form a confluent sheet and begin to stratify and differentiate. The tissue will then be raised to an air-liquid interface to promote differentiation.
Histological analysis. The conjunctival epithelial cell sheets on the amniotic membrane will be examined by light microscopy. Samples of the tissue will be fixed and processed with the use of standard histological procedures and stained with H\&E and PAS reagents. Electron microscopic examination will be carried for the tissue. The sections will also be subjected to immunohistochemical analysis for cytokeratin markers.
Clinical Transplantation of cultivated conjunctival epithelial cells on HAM
Preparation of cultivated conjunctival cells on amniotic membrane Patients with various ocular surface disorders will be selected for the initial series of transplantations. All patients will undergo full counselling for informed consent for the procedures. A forniceal conjunctival biopsy will be performed on the contralateral healthy eye. PI will perform the transplantations of autologous conjunctival sheet grown on human amniotic membrane in these patients. The diseased area will be excised using the standard surgical technique. The defect will be covered with the sheet of cultured conjunctival cells on the HAM with the epithelial side up. The graft is secured to the adjacent conjunctiva with interrupted 8/0 vicryl sutures. A planotherapeutic bandage contact lens is placed to protect the tissue from lid trauma. Topical steroid and antibiotic eyedrops will be administered daily to reduce the ocular inflammation. Survival of conjunctiva on the amniotic membrane will be closely monitored and patients will be followed-up at 3 monthly intervals up to one year. During these visits, these patients will have anterior segment photographs taken and fluorescein staining to monitor the progress of healing.
Transplantations may also be carried out on selected patients with ocular surface disease, for example, ocular cicatricial pemphigoid, Stevens Johnson syndrome and alkali injury. For these severe conditions, this procedure may prove to be an important adjunct to other procedures, such as limbal stem cell transplantation. If the initial study is successful, a randomised clinical trial comparing this procedure with conventional conjunctival autografting and conventional amniotic membrane transplantation will be planned. Therefore if found to be successful, transplantation of cultured conjunctival cells on HAM may eventually be used as a primary procedure or as an adjunctive procedure for these visually debilitating conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 21 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with ocular surface disorders, e.g. primary pterygium, scheduled for elective surgical excision
- Indications for surgery will be the presence of ocular surface symptoms in the affected eye, loss of visual acuity from visual axis obscuration or irregular astigmatism, or cosmesis.
- Only one eye of a patient will be eligible for study entry.
- Patients who are adult males and females who are aged 21 or older, and are considered mentally sound
- Patients who are willing to undergo long-term follow-up, as outlined in this protocol
Key exclusion criteria (8 listed)
- Patients less than 21 years of age
- Patients who are incapable, either by law or of mental state, of giving consent in their own right
- Patients who are either unable or unwilling to keep scheduled appointments and adhere to the other aspects of the protocol
- Patients who are pregnant or breastfeeding
- Patients with a history of drug allergy
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 |
|---|---|---|
| Cultivated conjunctival transplantation | Procedure or surgery | – |
Primary outcome
Epithelialisation
Graft integrity
Resolution of inflammation
Visual acuity
Complications
1 secondary outcome
Degree of scarring
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 13 Jan 2010.
- Results publication: PubMed 15161841Ang LP, Tan DT, Beuerman RW, Lavker RM. Development of a conjunctival epithelial equivalent with improved proliferative properties using a multistep serum-free culture system. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1789-95. doi: 10.1167/iovs.03-1361.
- Results publication: PubMed 15287367Ang LP, Tan DT, Phan TT, Li J, Beuerman R, Lavker RM. The in vitro and in vivo proliferative capacity of serum-free cultivated human conjunctival epithelial cells. Curr Eye Res. 2004 May;28(5):307-17. doi: 10.1076/ceyr.28.5.307.28677.
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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.
Leonard P Ang, FRCS principal investigator
SNEC, NUS
Donald T Tan, FRCS principal investigator
SNEC, SERI, NUS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cultivated conjunctival transplantation in people with Pterygium and Ocular Surface Disease, run by Singapore National Eye Centre at 1 site in Singapore.
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 6 inclusion and 8 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 13 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Epithelialisation. The study lists 5 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 NCT00346450, which also lists 2 linked publications.
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 13 Jan 2010; AzTrials last refreshed its copy on 7 Nov 2026.