The Improvement of Limbal Epithelial Culture Technique by Using Collagenase to Isolate Limbal Stem Cells

• ClinicalTrials.gov Identifier: NCT02202642
• Recruitment Status: Unknown
• First Posted: July 29, 2014
• Last Update Posted: July 29, 2014
• Sponsor: National Taiwan University Hospital
• Information provided by (Responsible Party): National Taiwan University Hospital

Study Description

Brief Summary:

Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell insufficiency based on the concept of "limbal stem cells need special cell-cell contact and cell-extracellular matrix interaction to support their survival".

Condition or disease	Intervention/treatment	Phase
Alkaline Chemical Burn Of Cornea And Conjunctival Sac; Acid Chemical Burn Of Cornea And Conjunctival Sac; Benign Mucous Membrane Pemphigoid With Ocular Involvement	Procedure: collagenase	Phase 1

Detailed Description:

Patients suffering from unilateral limbal stem cell insufficiency and understand the benefits and risk factors of the operation will be enrolled in this clinical trial. Two weeks before transplantation, the investigators first take 1-2 mm2 of limbal tissues from the healthy eye, digest the tissue with collagenase, and get an epithelial cell cluster. The cell cluster will be cultured on amniotic membrane with SHEM medium which contains Dulbecco's modified Eagle's medium/F12 (1:1), 5% dimethyl sulfoxide, 10 ng/ml human epidermal growth factor, 5μg/ml insulin, 0.5 μg/ml hydrocortisone, 1 nM cholera toxin, 50μg/ml gentamicin, 1.25μg/ml amphotericin B. Seven to ten days later after successful culture, transplantation will be performed after the cells reaches 1.5-2 cm2 compact confluent epithelial sheets without evidence of contamination. During the operation, lamellar keratectomy will be performed to remove the abnormal corneal neovascularization and scar tissue. The cultivated epithelial sheets will be transplanted to denuded corneal surface with fibrin glue and suture technique. The patients are planed to be admitted for 2 weeks. After discharge, follow up of the patients will be performed on one week, two week, one month, two months, three months, six months and one year later. Pictures of external eyes will be taken and the extent of corneal epithelium regeneration, visual acuity, and complications will be recorded during follow-up visits. The investigators plan to collect 10 patients.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Improvement of Limbal Epithelial Culture Technique for the Treatment of Unilateral Limbal Insufficiency by Using Collagenase to Isolate Limbal Stem Cells
• Study Start Date: January 2012
• Estimated Primary Completion Date: December 2015
• Estimated Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: limbal stem cells; Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment of patients suffering from unilateral limbal stem cell insufficiency based on the concept of "limbal stem cells need special cell-cell contact and cell-extracellular matrix interaction to support their survival"	Procedure: collagenase; Cultured limbal stem cells transplantation

Outcome Measures

Primary Outcome Measures :

1. Using collagenase to isolate limbal stem cells and improve the technique of ex vivo expansion of limbal stem cells for the treatment. [ Time Frame: 12 months ]
   Nine to twelve days later after successful culture, transplantation will be performed after the cells diameter reaches 1.5-2.0 cm compact confluent epithelial sheets without evidence of contamination.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age: between 18-70 years old.
2. Lesion eye should have limbal insufficiency more than 180 degrees.
3. Lesion eye should have recurrent corneal erosions, corneal neovascularisation and poor vision caused by limbal insufficiency.
4. The symptoms should be more than 1/2 year, and have no possibility of improvement by medical treatment.
5. The patients will to received the operation and the long term post- operative follow-up.
6. The patients are not infected by AIDS, hepatitis B/C , and willing to received the associated examinations.
7. The patients does not plan to be pregnant from the day of cell culture and transplantation for 1 year. They also agree to receive the pregnant test.
8. The condition of cell culture from the 1st to the clinical trial is successful.

Exclusion Criteria:

1. Bilateral limbal insufficiency.
2. No recurrent corneal erosion, corneal neovascularisation or poor vision was found due to limbal insufficiency. If corneal neovascularisation was found deeper than the anterior 1/2 of corneal stroma, or corneal thickness was less than 200 um evaluated by anterior segment OCT and ultrasound pachymetry, the patients should be excluded from the operation criteria. If corneal thickness becomes thicker, the patients can be enrolled for operation.
3. About corneal sedation, if the value checked by Cocet-Bonnet esthesiometer is less than 5 mm, the patients should be excluded from operation.
4. The condition can be improved by medication, or resolve spontaneously.
5. Post-operative follow up is less than 1/2 year
6. The patient can't receive long term postoperative follow up
7. No light perception, or can be expected to have very poor prognosis
8. If the intraocular pressure was more than 21 mmHg under necessary glaucoma surgery and anti-glaucoma medication, or optic disc cupping was more than 90%, or visual field was found to have severe defects, the patients were excluded from the clinical trial.
9. Severe lagophthalmos or trichiasis, and does not received blepharoplasty.
10. Severe dry eye syndrome. Those patients with schirmer's test result less than 1 mm should be excluded.
11. If the cells in the first part of the clinical trial can't be successfully cultivated, the patients should be excluded. If the patients insisted to received further treatment, they can be enrolled 3 months later.
12. Pregnancy

Contacts and Locations

Contacts

Contact: Wei Li Chen, MD, PhD; 886-2-23123456 ext 5206; chenweili@ntu.edu.tw

Locations

Taiwan

Wei-Li Chen; Recruiting

Taipei, Taiwan, 100

Sponsors and Collaborators

National Taiwan University Hospital

Investigators

• Principal Investigator: Wei Li Chen, MD, PhD; National Taiwan University Hospital

More Information

• Responsible Party: National Taiwan University Hospital, Wei-Li Chen/Assistant Professor, National Taiwan University, Department of Ophthalmology.
• ClinicalTrials.gov Identifier: NCT02202642
• Other Study ID Numbers: 201007032D
• First Posted: July 29, 2014
• Last Update Posted: July 29, 2014
• Last Verified: July 2014

Additional relevant MeSH terms:

Eye Burns; Corneal Diseases; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Burns, Chemical; Burns; Wounds and Injuries; Eye Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Autoimmune Diseases; Immune System Diseases; Conjunctival Diseases; Eye Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases