Labial Mucosal Epithelium Grafting for Corneal Limbus Substitution

NCT04995926 | Recruiting

• 1 other identifier: 517062021
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Limbal Stem-cell Deficiency

Keywords

Limbal Stem Cell Deficiency

Outcome Measures

Primary Outcomes (1)

• Anatomical success

  Presence of a stable epithelium on the cornea and absence of conjunctivalization in the visual axis of the recipient eye

  12 months

Secondary Outcomes (3)

• Number of participants with improvement in corneal status

  12 months

• Functional success

  12 months

• Rate of complications

  12 months

Study Arms (1)

Labial mucosa epithelium grafting for corneal limbus substitution.

EXPERIMENTAL

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.

Procedure: Labial mucosal epithelium grafting for corneal limbus substitution

Interventions

Labial mucosal epithelium grafting for corneal limbus substitution 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

Labial mucosa epithelium grafting for corneal limbus substitution.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• The S.N. Fyodorov Eye Microsurgery State Institution: lead

Study Sites (1)

The S. Fyodorov Eye Microsurgery Federal State Institution

Moscow, 127473, Russia

RECRUITING

Related Publications (14)

• 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

  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

  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.

  PMID: 32693830 BACKGROUND

• 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.

  PMID: 30688407 BACKGROUND

• 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.

  PMID: 30746908 BACKGROUND

• 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.

  PMID: 30614902 BACKGROUND

• 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.

  PMID: 32639314 BACKGROUND

• 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.

  PMID: 22333664 BACKGROUND

• 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.

  PMID: 31792300 BACKGROUND

• 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.

  PMID: 26016058 BACKGROUND

• 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.

  PMID: 21803325 BACKGROUND

• 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.

  PMID: 12506062 BACKGROUND

• 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.

  PMID: 15371576 BACKGROUND

• 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.

  PMID: 31936462 BACKGROUND

MeSH Terms

Conditions

Limbal Stem Cell Deficiency

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Study Officials

• Boris E Malyugin, MD PhD Prof

  The S. Fyodorov Eye Microsurgery Federal State Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Boris E. Malyugin, MD PhD Prof.

CONTACT

+7 (499) 488-85-11; boris.malyugin@gmail.com

Maksim Y Gerasimov, MD

CONTACT

+7 (499) 488-85-58; gerasimovmy@mntk.ru

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Director of Science

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 9, 2021
• Study Start: July 1, 2021
• Primary Completion: May 30, 2024
• Study Completion: December 31, 2025
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: During the study and after.
• Access Criteria: upon request

Locations

RU (1)