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Cell Therapy in Failure Syndromes in Limbal Stem Cells (TC181)

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ClinicalTrials.gov Identifier: NCT01619189
Recruitment Status : Unknown
Verified February 2015 by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts.
Recruitment status was:  Active, not recruiting
First Posted : June 14, 2012
Last Update Posted : February 4, 2015
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human amniotic membrane with no feeders in eyes with total limbal deficiency. Prospective non-comparative monocentric study.

Condition or disease Intervention/treatment Phase
Limbal Deficiency Biological: epithelial stem cells cultured Procedure: transplantation of cultured cells Phase 2

Detailed Description:
The limbal stem cell deficiency syndrome is characterized by invasion of the corneal surface by an epithelium with a conjunctival differentiation, and, clinically, by opacification and vascularization of the corneal epithelium with impaired corneal epithelial cicatrisation and corneal ulcers that may lead to corneal perforation. When total, the limbal deficiency syndrome is the cause of major disability. Vision decreases largely under the legal threshold of blindness. Overall, the most frequent etiology is by far the complete loss of limbal stem cells induced by severe ocular burns. Until a rather recent date, no treatment was possible in this pathology. Progress in the comprehension of the physiology of the corneal epithelium renewal made it possible to introduce a therapeutic approach, i.e., transplantation of cultured limbal stem cells retrieved from the healthy contralateral eye (autograft, unilateral diseases) or from a cadaveric donor eye (allograft, bilateral diseases or unique eye). Techniques of cell therapy were first described in Italy, Asia and in the USA with positive clinical results. They have all different processes for preparing the cell product to be transplanted and none answers the safety criteria required by the French legislation. The investigators developed a process for preparing a cell therapy product which was accepted by the French regulation agency (AFSSaPS) for a clinical trial (TC181) which began in 2007. The aims of the study are (1) evaluation of the clinical results of this technique in terms of improvement of visual function, reduction in the handicap, improvement of the anatomical condition of the ocular surface and restitution of the physiological function of the limbal epithelium and (2) evaluation of its possible side effects. It is a biphasic monocentric non-comparative prospective study including, according to the clinical responses observed during the first phase (plane of Gehan, ß = 10%), from 15 to 50 voluntary patients with unilateral or bilateral total limbal deficiency. Patient follow-up is 3 years. The expected minimal success rate is 20% for allografts and 40% for the autografts. Monitoring is ensured by URC-Est. The grafts are prepared by culture of autologous or allogeneic limbal epithelial cells from limbal explants on human amniotic membrane. The medical safety requirements relating to transplantation of tissues and cells are reached and the cell therapy products are secured at each stage of their preparation by conventional bacteriological and fungal tests and viral and bacterial PCR. The graft quality is controlled before transplantation. The main outcome measure is survival of the grafted epithelium (Kaplan-Meier method) defined by absence of recurrence of the clinical signs of limbal deficiency (opacification of the corneal epithelium, irregularity of the corneal epithelium, surface corneal vascularization) in the central cornea. The expected repercussions are (1) restitution of a limbal epithelial function allowing a clear corneal epithelium to be obtained, with no superficial vascularization nor chronic epithelial defects, (2) improvement of vision in blind patients, and (3) obtaining a vision higher than the legal threshold of blindness after cell therapy or after subsequent corneal transplantation. If the clinical trial makes it possible to show the effectiveness of this cell therapy technique, a request for authorization of process will be made at AFSSaPS for routine use.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Thérapie Cellulaire au Cours Des Syndromes d'Insuffisance en Cellules Souches Limbiques
Study Start Date : June 2007
Primary Completion Date : December 2014
Arms and Interventions

Intervention Details:
    Biological: epithelial stem cells cultured
    transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human amniotic membrane with no feeders
    Procedure: transplantation of cultured cells
    transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human amniotic membrane with no feeders

Outcome Measures

Primary Outcome Measures :
  1. survival of the transplanted epithelium [ Time Frame: 3 years ]
    survival of the transplanted epithelium defined by absence of recurrence of the clinical signs of limbal deficiency (opacification of the corneal epithelium, irregularity of the corneal epithelium, surface corneal vascularization) in the central cornea.


Secondary Outcome Measures :
  1. visual acuity [ Time Frame: 3 years ]
  2. re-epithelialization time after keratoplasty [ Time Frame: 3 years ]
    The healing time of corneal epithelium will be collectively assed by investigators form the CRF and the pictures taken during the study.

  3. Symptoms [ Time Frame: 3 years ]

    Symptoms recorded at each visit:

    • redness : absent (0) - present (1)
    • pain : absent (0) - present (1)
    • burning : absent (0) - present (1)
    • foreign body sensation : absent (0) - present (1)
    • photophobia : absent (0) - present (1)
    • blurred vision : absent (0) - present (1)

    Grading of symptoms : sum of all symptoms (0-6)


  4. morphometric analysis of the ocular surface [ Time Frame: 3 years ]
    the morphometric analysis of the corneal epithelial ulcerations will be assed by the CRA from the pictures of the corneal surface.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age between 18 and 70 years
  • Informed consent.
  • Unilateral or bilateral limbal deficiency with diffuse opacification of the corneal epithelium, and superficial (or superficial and deep) corneal vascularization, and irregular corneal epithelial surface at slit-lamp examination with fluorescein, either associated with chronic epithelial defects
  • Visual acuity of the eye to be treated < 20/20.
  • Absence de kératinization of the ocular surface.
  • Schirmer test > 0 at 3 minutes.
  • For autografts : sérology HIV -, HCV -, HBs

Exclusion Criteria:

  • Age < 18 y or > 70 y.
  • Absence of informed consent or imformed consent not possible.
  • Partial limbal deficiency (healthy corneal epithelium persistant in at least one zone).
  • Previous treatment of limbal deficiency by limbal transplantation or amniotic membrane transplantation during the last 12 months.
  • Conjunctival stem cell deficiency (xerophtalmia, keratinization of the ocular surface).
  • Local anesthesia impossible.
  • Immune keratitis not controlled by medical treatment.
  • Ocular burn during the last 2 weeks.
  • Corneal anesthesia.
  • Pregnancy, breast-feeding.
  • Allergy to steroid eyedrops.
  • Active fungal keratitis.
  • For autografts : risk factor for rabbies or Creutzfeldt-Jacob disease, serology HIV +, VHC +, HBs+.
  • Follow-up not possible
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01619189


Locations
France
CHNO des quinze-vingts
Paris, France, 75012
Sponsors and Collaborators
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Etablissement Français du Sang
More Information

Responsible Party: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
ClinicalTrials.gov Identifier: NCT01619189     History of Changes
Other Study ID Numbers: PHRC 2001
AOM01086 ( Other Identifier: AFSSAPS )
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: February 4, 2015
Last Verified: February 2015

Keywords provided by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:
Cell therapy
Limbal deficiency
Limbal stem cell
Transplantation