Cultivated Autologous Oral Mucosal Epithelial Transplantation

NCT ID: NCT03943797

Last Updated: 2020-08-13

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

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-01

Study Completion Date

2024-12-31

Brief Summary

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Earlier protocol for cultivated oral mucosal epithelial transplantation (COMET) requires trypsin/EDTA to isolate epithelial cells from tissue, and uses murine 3T3 cells as feeder cells, which results in biosafety concern. This study uses collagenase instead of trypsin/EDTA to isolate epithelial cells, and does not use 3T3 cells co-culture, so as to make an animal ingredient-free cell culture product. The purpose of the study is to evaluate the feasibility of the new protocol of COMET in clinical use.

Detailed Description

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When corneal epithelial stem cells are destroyed by severe trauma such as burn or autoimmune diseases, poor regeneration of corneal epithelium, persistent inflammatory reaction, neovascular ingrowth, and conjunctivalization may ensue, and seriously reduce the vision. In treating the diseased eye, when the other eye is healthy, limbal tissue containing corneal epithelial stem cells can be harvested for direct tissue transplantation, or ex vivo cultivation and expansion for several days before transplantation.

For patients with bilaterally damaged eyes, rejection rate in non-HLA matched allograft limbal stem cell transplantation is very high, in addition, adverse reaction to long-term immunosuppressive therapy may be life-threatening. Therefore, in 2004 Japanese researchers first proposed a novel technique to treat ocular surface diseases using cultivated autologous oral mucosal epithelial transplantation (COMET). From 2006 to 2009, investigators have also conducted a Phase I clinical trial approved by Taiwan FDA. In that Phase I trial, investigators have demonstrated efficacy of such cell therapy in promoting wound healing in patients with severe ocular surface burns (Ma DHK et al. Eye 2009; 23: 1442- 1450). Investigators have also identify long-term persistence of transplanted oral mucosal epithelial cells in the cornea (Chen HCJ et al. IOVS 2009;50:4660-4668), justifying this innovative surgical procedure as an effective alternative treatment modality.

However, in previous protocol, animal products such as fetal calf serum and 3T3 cell culture were used, raising the biosafety concern. For this, recently investigators have developed an animal ingredient-free cell culture protocol, and our protocol can meet the GTP standards, and has obtained the accreditation by Taiwan FDA and affiliated institutes. Therefore, the focus of current Phase Ib trial is to confirm the feasibility and safety of following items:

1. To produce cell culture product not containing animal ingredient, so as to avoid zoonoses. The oral mucosal epithelial cells thus cultured are used for treating ocular surface diseases with limbal stem cell deficiency.
2. To reduce recurrence of corneal neovascularization after COMET, Bevacizumab (Avastin) is injected locally, so as to improve corneal transparency and visual acuity.

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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Cultivated oral mucosal epithelial cell transplantation

Cell therapy for treating severe limbal stem cell deficiency using cultivated autologous oral mucosal epithelial cells.

Group Type EXPERIMENTAL

Cultivated oral mucosal epithelial cell transplantation

Intervention Type BIOLOGICAL

Cultivated oral mucosal epithelial cell transplantation (COMET) will be used to treat severe limbal stem cell deficiency so as to restore the integrity of corneal surface

Interventions

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Cultivated oral mucosal epithelial cell transplantation

Cultivated oral mucosal epithelial cell transplantation (COMET) will be used to treat severe limbal stem cell deficiency so as to restore the integrity of corneal surface

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Severe corneal epithelial deficiency
* Having favorable prognosis potential
* Normal of the intraocular pressure
* Normal of the light perception for the optic nerve
* No retinal diseases for the inflicted eyes
* No severe dry eye

Exclusion Criteria

* Having unfavorable prognosis potential
* Severe systemic disorders
* Unable to use daily vision
* Mentally retarded to execute permit on surgery
* Pregnant woman
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Chang Gung Memorial Hospital

OTHER

Sponsor Role lead

Responsible Party

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David Hui-Kang Ma

Attending Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David Hui-Kang Ma, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

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Core Laboratory for Cell Therapy, Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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David Hui-Kang Ma, MD, PhD

Role: CONTACT

03-328-1200 ext. 7840

Zheng Hua Huang, MSc

Role: CONTACT

03-328-1200 ext. 7840

Facility Contacts

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Su-Zeng Chen, Master

Role: primary

886-2-28712121 ext. 8455

References

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Chen HC, Chen HL, Lai JY, Chen CC, Tsai YJ, Kuo MT, Chu PH, Sun CC, Chen JK, Ma DH. Persistence of transplanted oral mucosal epithelial cells in human cornea. Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4660-8. doi: 10.1167/iovs.09-3377. Epub 2009 May 20.

Reference Type RESULT
PMID: 19458337 (View on PubMed)

Chen HC, Yeh LK, Tsai YJ, Lai CH, Chen CC, Lai JY, Sun CC, Chang G, Hwang TL, Chen JK, Ma DH. Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation. Invest Ophthalmol Vis Sci. 2012 Aug 17;53(9):5615-23. doi: 10.1167/iovs.11-9293.

Reference Type RESULT
PMID: 22850415 (View on PubMed)

Inatomi T, Nakamura T, Koizumi N, Sotozono C, Yokoi N, Kinoshita S. Midterm results on ocular surface reconstruction using cultivated autologous oral mucosal epithelial transplantation. Am J Ophthalmol. 2006 Feb;141(2):267-275. doi: 10.1016/j.ajo.2005.09.003.

Reference Type RESULT
PMID: 16458679 (View on PubMed)

Inatomi T, Nakamura T, Kojyo M, Koizumi N, Sotozono C, Kinoshita S. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol. 2006 Nov;142(5):757-64. doi: 10.1016/j.ajo.2006.06.004. Epub 2006 Sep 20.

Reference Type RESULT
PMID: 16989763 (View on PubMed)

Li W, Sabater AL, Chen YT, Hayashida Y, Chen SY, He H, Tseng SC. A novel method of isolation, preservation, and expansion of human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2007 Feb;48(2):614-20. doi: 10.1167/iovs.06-1126.

Reference Type RESULT
PMID: 17251457 (View on PubMed)

Ma DH, Kuo MT, Tsai YJ, Chen HC, Chen XL, Wang SF, Li L, Hsiao CH, Lin KK. Transplantation of cultivated oral mucosal epithelial cells for severe corneal burn. Eye (Lond). 2009 Jun;23(6):1442-50. doi: 10.1038/eye.2009.60. Epub 2009 Apr 17.

Reference Type RESULT
PMID: 19373264 (View on PubMed)

Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004 Oct;88(10):1280-4. doi: 10.1136/bjo.2003.038497.

Reference Type RESULT
PMID: 15377551 (View on PubMed)

Nakamura T, Takeda K, Inatomi T, Sotozono C, Kinoshita S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011 Jul;95(7):942-6. doi: 10.1136/bjo.2010.188714. Epub 2010 Nov 19.

Reference Type RESULT
PMID: 21097786 (View on PubMed)

Petsoglou C, Balaggan KS, Dart JK, Bunce C, Xing W, Ali RR, Tuft SJ. Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. Br J Ophthalmol. 2013 Jan;97(1):28-32. doi: 10.1136/bjophthalmol-2012-302137. Epub 2012 Oct 20.

Reference Type RESULT
PMID: 23087419 (View on PubMed)

Satake Y, Higa K, Tsubota K, Shimazaki J. Long-term outcome of cultivated oral mucosal epithelial sheet transplantation in treatment of total limbal stem cell deficiency. Ophthalmology. 2011 Aug;118(8):1524-30. doi: 10.1016/j.ophtha.2011.01.039. Epub 2011 May 14.

Reference Type RESULT
PMID: 21571372 (View on PubMed)

Takeda K, Nakamura T, Inatomi T, Sotozono C, Watanabe A, Kinoshita S. Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease. Am J Ophthalmol. 2011 Aug;152(2):195-201.e1. doi: 10.1016/j.ajo.2011.01.046. Epub 2011 Jun 8.

Reference Type RESULT
PMID: 21652025 (View on PubMed)

Hsueh YJ, Huang SF, Lai JY, Ma SC, Chen HC, Wu SE, Wang TK, Sun CC, Ma KS, Chen JK, Lai CH, Ma DH. Preservation of epithelial progenitor cells from collagenase-digested oral mucosa during ex vivo cultivation. Sci Rep. 2016 Nov 8;6:36266. doi: 10.1038/srep36266.

Reference Type RESULT
PMID: 27824126 (View on PubMed)

Ma DH, Hsueh YJ, Ma KS, Tsai YJ, Huang SF, Chen HC, Sun CC, Kuo MT, Chao AS, Lai JY. Long-term survival of cultivated oral mucosal epithelial cells in human cornea: generating cell sheets using an animal product-free culture protocol. Stem Cell Res Ther. 2021 Oct 7;12(1):524. doi: 10.1186/s13287-021-02564-7.

Reference Type DERIVED
PMID: 34620226 (View on PubMed)

Other Identifiers

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101CONS12640

Identifier Type: -

Identifier Source: org_study_id

NCT02739113

Identifier Type: -

Identifier Source: nct_alias

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