Transplantation of Autologous Oral Mucosal Epithelial Sheets for Limbal Stem-cell Deficiency

Phase 1

Completed

• Conditions: Limbal Stem-cell Deficiency
• Interventions: Biological: Mucosal cell sheet transplantation

• Registration Number: NCT02415218
• Lead Sponsor: Siriraj Hospital

Brief Summary

The study purpose is to evaluate the efficacy and safety of cultivated oral mucosal epithelial sheet transplantation as a novel therapy for limbal stem cell deficiency, for which no effective approaches has thus far been available, for the purpose of establishing this therapy as an effective strategy for this disease with an aim of improving visual acuity and corneal transparency.

Detailed Description

The efficacy and safety of cultivated oral mucosal epithelial sheet transplantation as a novel therapy for limbal stem-cell deficiency, for which no effective approaches have thus far been available, will be evaluated for the purpose of establishing this therapy as an effective strategy for this disease with an aim of improving visual acuity and corneal transparency. The primary endpoint will be an area of no conjunctivalization and no corneal epithelial defect at one year, which will be evaluated according to a 6-grade rating scale. The secondary endpoints will be corrected visual acuity, severity of corneal opacification, extent of corneal neovascularization, expected ocular complications, and all adverse events including abnormal laboratory findings. The purpose of this research is to evaluate the efficacy of the investigational therapy so as to provide rationales for making this strategy approved as an advanced medical care in the future.

Study Timeline

• Study Start: 2013-04-17
• Study First Submitted: 2015-04-08
• Study First Submitted QC: 2015-04-13
• Study First Posted: 2015-04-14
• Primary Completion: 2016-09-03
• Study Completion: 2017-04-16
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-10
• Last Update Posted: 2019-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Among patients with bilateral limbal stem-cell deficiency, those who meet all the criteria listed below when they give their informed consent to participate in this research will be included.

  1. Patients in whom the eye(s) (subject to the interventional therapy) show(s) loss or dysfunction of corneal epithelial stem cells throughout the total* circumference of the cornea
  2. Patients in whom the corneal surface of the eye(s) (subject to the investigational therapy) is(are) entirely enveloped by conjunctival tissue
  3. Patients of both genders aged ≥20 years when they give their informed consent
  4. Patients who have given their own written consent to participate in this clinical research (The target disease is bilateral limbal stem-cell deficiency, although it is not always necessary that the both eyes of the patient meet the inclusion criteria.)

Exclusion Criteria

1. Patients who are or may be pregnant, and patients who are breast feeding
2. Patients with infections (HBV, HCV, HIV, HTLV-1)
3. Patients with extreme hypolacrimation resistant to therapy
4. Patients from whom oral mucosal specimens cannot be collected because clear scar formation or inflammatory findings are noted in a cell-collection site of the mucosal membrane
5. Patients whose score of Performance Status (PS*) is 3 or more
6. Any others who are judged by the chief subinvestigator to be ineligible for this clinical research, due to the presence of complications, etc.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mucosal cell sheet transplantation	Mucosal cell sheet transplantation	The subjects will have their oral mucosal tissues retrieved for cell sheet preparation. The mucosal cell sheet will be transplanted over the affected cornea.

Primary Outcome Measures

Name	Time	Method
Evaluation of conjunctivalization and corneal epithelial defect	1 year after transplantation	One year after the transplantation, an area of no conjunctivalization and no corneal epithelial defect will be rated according to the Grading scale described in Table 2, on the basis of which the efficacy of the investigational therapy will be assessed. Generally, the preoperative condition of ocular surface is rated as "Bad (Grading 0)." In subjects showing improvement to Grading 2 or greater, the investigational therapy will be assessed as effective.

Secondary Outcome Measures

Name	Time	Method
Corrected visual acuity (efficacy)	1 year	Corrected visual acuity will be evaluated by the decimal acuity method and converted to Log MAR values, which will be used to assess the extent of postoperative change in visual acuity. Note that 0.005 will be given to "counting fingers," 0.002, to "hand motion," and 0.001, to "light perception" 14). Visual acuity will be measured before transplantation, and 1, 3, and 6 months as well as one year after transplantation.

Trial Locations

Locations (1)

Siriraj Clinical Research Center, Siriraj Hospital; 🇹🇭 Bangkoknoi, Bangkok, Thailand