Stem Cells Treatment for Bilateral Limbic Associated Keratopathy (HULPOFT)

Keratopathy Clinical Trial

— HULPOFT  

Official title:

Phase IIa Clinical Trial to Study the Feasability and Security of the Expanded Autologous Stem Cells (ASC) From Lipoaspirate in the Bilateral Limbic Associated Keratopathy Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01808378
• Other study ID #: HULPOFT-2010-01
• Secondary ID: 2010-024328-53
• Status: Recruiting
• Phase: Phase 2
• First received: September 4, 2012
• Last updated: March 7, 2013
• Start date: February 2013
• Est. completion date: December 2014

Study information

• Verified date: September 2012
• Source: Instituto de Investigación Hospital Universitario La Paz
• Contact: Mariano García-Arranz, PhD
• Phone: 0034 912071022
• Email: mgarciaa.hulp[@]salud.madrid.org
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

Evaluate the use of the autologous ASC for the treatment of bilateral limbic associated keratopathy

Description:

Intralesional use by inject of adipose derived stem cells

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. -Signed informed consent

2. -Previously diagnosed bilateral limbic obstruction

3. -Men and women over 18 years old. Good general state of health according to the findings of the clinical history and the physical examination

4. -Suffering chronic keratopathy accomplishing the following criteria:

• Confirmed limbic obstruction with an impression cytology

• Repeated usual treatment failure for this pathology

Exclusion Criteria:

1. -Having suffered a neoplasia in the previous 5 years

2. -Local anesthesia allergies

3. -Patients having participate in any other study in the previous 90 days to the inclusion

4. -Patients on medication with tacrolimus or cyclosporine in the 4 previous week to the cellular therapy

5. -Any medical or psychiatric illness that, in the investigator opinion, could suppose a reason for the study exclusion

6. -Patients with any type of medical or psychiatric disease which, in the opinion of the investigator, could be grounds for exclusion from study

7. -Patients with congenital or acquired immunodeficiencies. HIV, HBV, HCV or treponema infection, whether active or latent

8. -Patients who have suffering major surgery or severe trauma in the prior 6 months

9. -Pregnant or breastfeeding women

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Keratopathy

Intervention

Drug:
• Expanded adipose-derived stem cells
Local injection of autologousadipose derived stem cells

Locations

Country	Name	City	State
Spain	Hospital Universitario La Paz	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigación Hospital Universitario La Paz

Country where clinical trial is conducted

Spain, 

References & Publications (23)

Arnalich-Montiel F, Pastor S, Blazquez-Martinez A, Fernandez-Delgado J, Nistal M, Alio JL, De Miguel MP. Adipose-derived stem cells are a source for cell therapy of the corneal stroma. Stem Cells. 2008 Feb;26(2):570-9. Epub 2007 Dec 6. — View Citation

Arntz Bustos A, Durán de la Colina JA. Anatomía funcional de la superficie ocular. En; Superficie Ocular. Ed S.E.O. 2004; 1-12

Blazejewska EA, Schlötzer-Schrehardt U, Zenkel M, Bachmann B, Chankiewitz E, Jacobi C, Kruse FE. Corneal limbal microenvironment can induce transdifferentiation of hair follicle stem cells into corneal epithelial-like cells. Stem Cells. 2009 Mar;27(3):642-52. doi: 10.1634/stemcells.2008-0721. — View Citation

Chen JJ, Tseng SC. Corneal epithelial wound healing in partial limbal deficiency. Invest Ophthalmol Vis Sci. 1990 Jul;31(7):1301-14. — View Citation

Daya SM, Watson A, Sharpe JR, Giledi O, Rowe A, Martin R, James SE. Outcomes and DNA analysis of ex vivo expanded stem cell allograft for ocular surface reconstruction. Ophthalmology. 2005 Mar;112(3):470-7. — View Citation

Gu S, Xing C, Han J, Tso MO, Hong J. Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo. Mol Vis. 2009;15:99-107. Epub 2009 Jan 16. — View Citation

Ilari L, Daya SM. Long-term outcomes of keratolimbal allograft for the treatment of severe ocular surface disorders. Ophthalmology. 2002 Jul;109(7):1278-84. — View Citation

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. — View Citation

Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989 May;96(5):709-22; discussion 722-3. — View Citation

Lehrer MS, Sun TT, Lavker RM. Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation. J Cell Sci. 1998 Oct;111 ( Pt 19):2867-75. — View Citation

Ma Y, Xu Y, Xiao Z, Yang W, Zhang C, Song E, Du Y, Li L. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells. 2006 Feb;24(2):315-21. Epub 2005 Aug 18. — View Citation

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. — View Citation

Nakamura T, Kinoshita S. Ocular surface reconstruction using cultivated mucosal epithelial stem cells. Cornea. 2003 Oct;22(7 Suppl):S75-80. — View Citation

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. — View Citation

Nishida K. Tissue engineering of the cornea. Cornea. 2003 Oct;22(7 Suppl):S28-34. Review. — View Citation

Pellegrini G, De Luca M, Arsenijevic Y. Towards therapeutic application of ocular stem cells. Semin Cell Dev Biol. 2007 Dec;18(6):805-18. Epub 2007 Sep 16. Review. — View Citation

Samson CM, Nduaguba C, Baltatzis S, Foster CS. Limbal stem cell transplantation in chronic inflammatory eye disease. Ophthalmology. 2002 May;109(5):862-8. — View Citation

Santos MS, Gomes JA, Hofling-Lima AL, Rizzo LV, Romano AC, Belfort R Jr. Survival analysis of conjunctival limbal grafts and amniotic membrane transplantation in eyes with total limbal stem cell deficiency. Am J Ophthalmol. 2005 Aug;140(2):223-30. — View Citation

Schermer A, Galvin S, Sun TT. Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol. 1986 Jul;103(1):49-62. — View Citation

Tan DT, Ficker LA, Buckley RJ. Limbal transplantation. Ophthalmology. 1996 Jan;103(1):29-36. — View Citation

Tseng SC. Staging of conjunctival squamous metaplasia by impression cytology. Ophthalmology. 1985 Jun;92(6):728-33. — View Citation

Tsubota K, Toda I, Saito H, Shinozaki N, Shimazaki J. Reconstruction of the corneal epithelium by limbal allograft transplantation for severe ocular surface disorders. Ophthalmology. 1995 Oct;102(10):1486-96. — View Citation

Yao YF, Inoue Y, Miyazaki K, Shimoura Y, Ohashi Y, Tano Y. Ocular resurfacing and alloepithelial suface reconstruction. Ophthalmol 2005; 112: 470-7

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the practicability and security of the autologous expanded lipoaspirated stem cells for the treatment of bilateral limbic associated keratopathy	Micro ocular Photography Visual acuity	16 weeks	No
Secondary	Quality of life assessment using the SF-12 Questionnaire	SF-12 questionnaire	1, 4, 16, 24 weeks	No
Secondary	Adverse events	Data collection	1, 4, 16, 24 weeks	Yes