Labial Mucosal Epithelium Grafting for Corneal Limbus Substitution

NCT ID: NCT04995926

Last Updated: 2024-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-01

Study Completion Date

2025-12-31

Brief Summary

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Earlier approaches for cornea reepithelization in patients with bilateral LSCD included allogeneic corneal limbus grafting from postmortem donor or livingrelated relatives with concomitant systemic immunosuppression (Cheung and Holland, 2017) and cultivated oral mucosal epithelial transplantation (COMET) (Nishida et al., 2004).

The novel surgical technique for corneal re-epithelization were described by Liu et al. (2011) and Choe et al. (2019). In both clinical studies, the autologous labial mucosal epithelium graft was transplanted as a surrogate corneal limbus for purpose of treatment the LSCD. Authors reported positive outcomes in terms of anatomical success and corneal status improvement.

The purpose of the study is to evaluate the feasibility of the novel surgical intervention in clinical use.

Detailed Description

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Earlier approaches for cornea reepithelization in patients with bilateral LSCD included allogeneic corneal limbus grafting from postmortem donor or livingrelated relatives with concomitant systemic immunosuppression (Cheung and Holland, 2017) and cultivated oral mucosal epithelial transplantation (COMET) (Nishida et al., 2004).

The novel surgical technique for corneal re-epithelization were described by Liu et al. (2011) and Choe et al. (2019). In both clinical studies, the autologous labial mucosal epithelium graft was transplanted as a surrogate corneal limbus for purpose of treatment the LSCD. Authors reported positive outcomes in terms of anatomical success and corneal status improvement.

Lip oral mucosa is a promising autologous source of epithelial cell for the trial because it has similar histological characteristic as the normal corneal. In particular, lip oral mucosal epithelium is stratified squamous and nonkeratinized.

The indicated histological and molecular features of the lip oral mucosal epithelium predetermined the use of labial mucosal epithelial graft for treatment patients with bilateral LSCD.

The purpose of the study is to confirm the validity of the hypothesis about the possibility of re-epithelialization diseased cornea using labial mucosal epithelium graft as a surrogate limbus in patients with bilateral LSCD.

Conditions

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Limbal Stem-cell Deficiency

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Labial mucosa epithelium grafting for corneal limbus substitution.

Surgery for treating limbal stem cell deficiency using a strip of the lip oral mucosa with trimmed off the substantia propria and grafted as a circular corneal limbus substitute.

Group Type EXPERIMENTAL

Labial mucosal epithelium grafting for corneal limbus substitution

Intervention Type PROCEDURE

Labial mucosa epithelium grafting for corneal limbus substitution will be used to treat limbal stem cell deficiency by way of corneal surface re-epithelization

Interventions

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Labial mucosal epithelium grafting for corneal limbus substitution

Labial mucosa epithelium grafting for corneal limbus substitution will be used to treat limbal stem cell deficiency by way of corneal surface re-epithelization

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Man or woman 18 years and older.
* Signed informed consent, given by the participant or his/her legal representative.
* Ability to understand Russian spoken and written language.
* Sanitated oral cavity.
* Bilateral limbal stem cell deficiency diagnosed by two or more symptoms during slit-lamp examination: corneal conjunctivalization, absence of palisades of Vogt, superficial corneal neovascularization, recurrent or persistent corneal epithelium erosion.
* Bilateral limbal stem cell deficiency non-immunogenic etiology (burns, irradiation, contact lens related, etc.).
* Best-corrected visual acuity less than 0.3 (6/18 Snellen chart)
* Intraocular pressure in normal range.
* Schirmer's test I more than 5 mm.

Exclusion Criteria

* Inability to give signed informed consent.
* Age under 18 years.
* Pregnancy and/or breastfeeding.
* Hormonal contraceptives intake.
* History of allergic reactions to antibiotics, glucocorticosteroids, remedies for treatment dry eye syndrome, medications for local and general anesthesia.
* Participation in other clinical trials.
* Systemic immunosuppression intake.
* Diagnosed neoplastic process or treatment for it.
* Positive tests for infectious: HIV, syphilis, Hepatitis B, Hepatitis C.
* Any medical, psychiatric and/or condition, including cachexia, or social conditions that the investigator believes would interfere with or contraindicate adherence to the research protocol or the ability to provide signed informed consent.
* Immune-mediated limbal stem cell deficiency (Stevens-Johnson syndrome, ocular cicatricial pemphigoid and other.), unknown and/or inherited etiology.
* Best-corrected visual acuity more than 0.3 (6/18 Snellen chart)
* Ocular burns earlier than 12 months.
* Keratoplasty earlier than 12 months.
* Limbal grafting (from postmortem or living-related donors).
* Keratoprosthetic device or history of its implantation.
* Cellular therapy for treatment of limbal stem cell deficiency.
* Cellular transplantation for treatment of limbal stem cell deficiency.
* Active ophthalmic infection.
* Symblepharon, ectropion, trichiasis, lagophthalmos and/or other lid and/or conjunctival fornixes abnormalities.
* Surgery on ocular adnexa earlier than 9 months.
* Corneal stromal thickness less than 300 mkm.
* Dry eye with Schirmer test I less than 5 mm and/or keratinized ocular surface.
* Uncontrolled glaucoma and/or presents of a glaucoma drainage device.
* Retinal defunctioning (no light perception and/or retinal detachment).
* Absence of the electric activity of the optic nerve and/or retina.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The S.N. Fyodorov Eye Microsurgery State Institution

OTHER_GOV

Sponsor Role lead

Responsible Party

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Boris Malyugin

Deputy Director of Science

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Boris E Malyugin, MD PhD Prof

Role: PRINCIPAL_INVESTIGATOR

The S. Fyodorov Eye Microsurgery Federal State Institution

Locations

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The S. Fyodorov Eye Microsurgery Federal State Institution

Moscow, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Boris E. Malyugin, MD PhD Prof.

Role: CONTACT

+7 (499) 488-85-11

Maksim Y Gerasimov, MD

Role: CONTACT

+7 (499) 488-85-58

Facility Contacts

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Boris E. Boris, MD PhD Prof.

Role: primary

+7 (499) 488-85-11

Maksim Y Gerasimov

Role: backup

+7 (499) 488-85-58

References

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Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, Pellegrini G, Shimmura S, Kruse FE; and The International Limbal Stem Cell Deficiency Working Group. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea. 2019 Mar;38(3):364-375. doi: 10.1097/ICO.0000000000001820.

Reference Type BACKGROUND
PMID: 30614902 (View on PubMed)

Deng SX, Kruse F, Gomes JAP, Chan CC, Daya S, Dana R, Figueiredo FC, Kinoshita S, Rama P, Sangwan V, Slomovic AR, Tan D; and the International Limbal Stem Cell Deficiency Working Group. Global Consensus on the Management of Limbal Stem Cell Deficiency. Cornea. 2020 Oct;39(10):1291-1302. doi: 10.1097/ICO.0000000000002358.

Reference Type BACKGROUND
PMID: 32639314 (View on PubMed)

Holland EJ, Mogilishetty G, Skeens HM, Hair DB, Neff KD, Biber JM, Chan CC. Systemic immunosuppression in ocular surface stem cell transplantation: results of a 10-year experience. Cornea. 2012 Jun;31(6):655-61. doi: 10.1097/ICO.0b013e31823f8b0c.

Reference Type BACKGROUND
PMID: 22333664 (View on PubMed)

Inamochi A, Tomioka A, Kitamoto K, Miyai T, Usui T, Aihara M, Yamagami S. Simple oral mucosal epithelial transplantation in a rabbit model. Sci Rep. 2019 Dec 2;9(1):18088. doi: 10.1038/s41598-019-54571-7.

Reference Type BACKGROUND
PMID: 31792300 (View on PubMed)

Li W, Li Q, Wang W, Li K, Ling S, Yang Y, Liang L. A rat model of autologous oral mucosal epithelial transplantation for corneal limbal stem cell failure. Eye Sci. 2014 Mar;29(1):1-5.

Reference Type BACKGROUND
PMID: 26016058 (View on PubMed)

Liu J, Sheha H, Fu Y, Giegengack M, Tseng SC. Oral mucosal graft with amniotic membrane transplantation for total limbal stem cell deficiency. Am J Ophthalmol. 2011 Nov;152(5):739-47.e1. doi: 10.1016/j.ajo.2011.03.037. Epub 2011 Jul 30.

Reference Type BACKGROUND
PMID: 21803325 (View on PubMed)

Nakamura T, Endo K, Cooper LJ, Fullwood NJ, Tanifuji N, Tsuzuki M, Koizumi N, Inatomi T, Sano Y, Kinoshita S. The successful culture and autologous transplantation of rabbit oral mucosal epithelial cells on amniotic membrane. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):106-16. doi: 10.1167/iovs.02-0195.

Reference Type BACKGROUND
PMID: 12506062 (View on PubMed)

Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, Tano Y. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. N Engl J Med. 2004 Sep 16;351(12):1187-96. doi: 10.1056/NEJMoa040455.

Reference Type BACKGROUND
PMID: 15371576 (View on PubMed)

Oliva J, Bardag-Gorce F, Niihara Y. Clinical Trials of Limbal Stem Cell Deficiency Treated with Oral Mucosal Epithelial Cells. Int J Mol Sci. 2020 Jan 9;21(2):411. doi: 10.3390/ijms21020411.

Reference Type BACKGROUND
PMID: 31936462 (View on PubMed)

Malyugin B.E., Borzenok S.A., Gerasimov M.Y. Clinical outcomes of autologous cultured oral mucosal epithelium transplantation for treatment of limbal stem cell deficiency. Fyodorov Journal of Ophthalmic Surgery. 2020;(4):77-85. (In Russ.) doi:10.25276/0235-4160-2020-4-77-85

Reference Type BACKGROUND

Borzenok S.A., Gerasimov M.Yu., Ostrovskiy D.S., Malyugin B.E. Culture of human labial mucosal epithelial cell for use in patients with bilateral limbal stem cell deficiency. Russian Journal of Transplantology and Artificial Organs. 2019;21(3):111-120. doi:10.15825/1995-1191-2019-3-111-120

Reference Type BACKGROUND

Cabral JV, Jackson CJ, Utheim TP, Jirsova K. Ex vivo cultivated oral mucosal epithelial cell transplantation for limbal stem cell deficiency: a review. Stem Cell Res Ther. 2020 Jul 21;11(1):301. doi: 10.1186/s13287-020-01783-8.

Reference Type BACKGROUND
PMID: 32693830 (View on PubMed)

Campbell JDM, Ahmad S, Agrawal A, Bienek C, Atkinson A, Mcgowan NWA, Kaye S, Mantry S, Ramaesh K, Glover A, Pelly J, MacRury C, MacDonald M, Hargreaves E, Barry J, Drain J, Cuthbertson B, Nerurkar L, Downing I, Fraser AR, Turner ML, Dhillon B. Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial. Stem Cells Transl Med. 2019 Apr;8(4):323-331. doi: 10.1002/sctm.18-0140. Epub 2019 Jan 28.

Reference Type BACKGROUND
PMID: 30688407 (View on PubMed)

Choe HR, Yoon CH, Kim MK. Ocular Surface Reconstruction Using Circumferentially-trephined Autologous Oral Mucosal Graft Transplantation in Limbal Stem Cell Deficiency. Korean J Ophthalmol. 2019 Feb;33(1):16-25. doi: 10.3341/kjo.2018.0111.

Reference Type BACKGROUND
PMID: 30746908 (View on PubMed)

Other Identifiers

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517062021

Identifier Type: -

Identifier Source: org_study_id

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