Clinical trial NCT03217435: Corneal Epithelial Allograft From Living-related Donor for LSCD
Official title: A Non-randomized Controlled Clinical Trial of Epithelial Allograft Transplantation From Living-related Donors for the Treatment of Limbal Stem Cell Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Limbal Stem Cell Deficiency
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-07-14
Enrollment: 20
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to explore whether femtosecond laser-assisted corneal epithelial allograft from living-related donor is more effective than limbal conjunctival allograft from living-related donor for ocular surface reconstruction in patients with limbal stem cell deficiency (LSCD).


Eligibility criteria: Inclusion Criteria:

1. LSCD secondary to ocular burns, with the duration of disease of at least 24 months at the time of screening visit;
2. Presence of superficial neo-vascularization affecting at least 2 cornea quadrants and involving central cornea;
3. Having a human leukocyte antigen (HLA)-matched living-related donor (≥4/6 HLA-A/B/DR matched);
4. Informed consent signed by patient or legal guardian. Having the ability to comply with study assessments for the full duration of the study.

Exclusion Criteria:

Recipients:

1. LSCD of mild degree, with less than 2 quadrants of neo-vessel invasion and without central cornea involvement;
2. LSCD by ocular surface disorders other than ocular burn;
3. Eyelids malposition;
4. The center corneal thickness\<450µm, the depth of corneal opacity \> 150µm;
5. High myopia with a spherical equivalent of -15.0 D or less;
6. Corneal or ocular surface infection within 30 days prior to study entry;
7. Ocular surface malignancy;
8. Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%;
9. Renal failure with creatinine clearance\< 25ml/min;
10. Alanine aminotransferase \> 40IU/L, or aspartate aminotransferase \> 40IU/L;
11. Platelet levels \< 150,000 or \> 450,000 per microliter;
12. Hemoglobin \< 12.0 g/dL (male) or \< 11.0 g/dL (female);
13. Prothrombin time \> 16s and activated partial thrombin time \> 35s in patients not accepting anticoagulant therapy; An international normalized ratio greater than 3 in patients accepting anticoagulant therapy;
14. Pregnancy (positive test) or lactation;
15. Participation in another simultaneous medical investigation or clinical trial;
16. Severe cicatricial eye disease; Conjunctival scarring with fornix shortening;
17. Ocular comorbidities that affect the prognosis of transplantation, such as advanced glaucoma or retinal diseases;
18. Severe dry eye disease as determined by Schirmer's test \< 2mm at least in one eye;
19. Any medical or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent;
20. Signs of current infection, including fever and treatment with antibiotics;
21. Active immunological diseases;
22. History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

Donors:

1. Cornea diseases (epithelial defects, neovascularization, etc.);
2. Eyelids malposition;
3. The center corneal thickness\<450µm, the depth of corneal opacity \> 150µm;
4. High myopia with a spherical equivalent of -15.0 D or less;
5. Corneal or ocular surface infection within 30 days prior to study entry;
6. Ocular surface malignancy;
7. Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%;
8. Renal failure with creatinine clearance\< 25ml/min;
9. Alanine aminotransferase \> 40IU/L, or aspartate aminotransferase \> 40IU/L;
10. Platelet levels \< 150,000 or \> 450,000 per microliter;
11. Hemoglobin \< 12.0 g/dL (male) or \< 11.0 g/dL (female);
12. Prothrombin time \> 16s and activated partial thrombin time \> 35s in patients not accepting anticoagulant therapy; An international normalized ratio greater than 3 in patients accepting anticoagulant therapy;
13. Pregnancy (positive test) or lactation;
14. Participation in another simultaneous medical investigation or clinical trial;
15. Severe cicatricial eye disease; Conjunctival scarring with fornix shortening;
16. Ocular comorbidities that affect the prognosis of transplantation, such as advanced glaucoma or retinal diseases;
17. Severe dry eye disease as determined by Schirmer's test \< 2mm at least in one eye;
18. Any medical or social condition that in the judgment of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent;
19. Signs of current infection, including fever and treatment with antibiotics;
20. Active immunological diseases;
21. History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

Primary outcomes:
measure: Restoration of corneal surface in the recipient
timeFrame: 1 year
measure: Restoration of corneal surface in the donor
timeFrame: 1 year
Secondary outcomes:
measure: Uncorrected and best-corrected visual acuity of recipients and donors
timeFrame: 1 year
measure: Corneal power, astigmatism and aberration of recipients and donors
timeFrame: 1 year
measure: Corneal sensation of recipients and donors
timeFrame: 1 year
measure: Corneal thickness of recipients and donors
timeFrame: 1 year
measure: Density of stromal nerve and stromal keratocytes of recipients and donors
timeFrame: 1 year
measure: Reconstruction of limbal palisades of Vogt of recipients
timeFrame: 1 year
measure: Corneal graft rejection of recipients
timeFrame: 1 year
measure: Corneal haze of recipients and donors
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-sen Univerisity
state: Guangdong
Study officials:
affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University
name: Yizhi Liu, M.D.Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University
name: Ting Huang, M.D.Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: