Safety Study of Stem Cell Transplant to Treat Limbus Insufficiency Syndrome

Advanced Therapy for Ocular Surface Reconstruction. Allogenic Limbus Epithelial Stem-cell Transplant vs Bone Marrow Mesenchymal Stem-cell Transplant in Limbus Insufficiency Syndrome. Double-masked Randomized Trial

The purpose of the study is to determine whether allogenic bone marrow stem cell transplant is safe and effective in the treatment of limbus insufficiency syndrome versus allogenic limbus stem cell transplant.

Study Overview

• Status: Completed
• Conditions: Limbus Corneae Insufficiency Syndrome
• Intervention / Treatment: Procedure: Stem Cell with Amniotic Membrane Transplant

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Valladolid, Spain, 47011
    • IOBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female older than 18 years.
• Signed Informed consent
• Negative pregnancy test at inclusion for any potential childbearing female.
• Compromise of contraceptive method during all trial for any potential childbearing female.
• Diagnosis of Ocular Surface Failure due to Limbus Insufficiency Syndrome, based in any of the published characteristics as corneal surface neovascularization, loss of corneal transparency, epithelial irregularities, history of punctate keratitis, erosions or repetitive ulcers and presence of symptoms and confirmed by the presence of epithelial phenotype cells assessed with conjunctival impression cytology.
• Availability for all the scheduled visits during the study

Exclusion Criteria:

• Uncontrolled systemic disease (e.g. hypertension or diabetes) or any disease that under medical decision might put the patient at risk during the surgery or follow-up examinations or may cause any hazard in data analysis.
• Active ocular infection in any eye. If the infection can be cured, inclusion can be considered after 30 days of inactive infection since its end.
• Alterations in lid statics / dynamics or any other pathology (e.g. severe dry eye syndrome) except the one that originated the Limbus Insufficience that under medical opinion might alter the results. Any of these must be corrected 3 months prior to patient inclusion, before reconsidering rescreening.
• Limbus insufficiency syndrome which has not been previously treated with all medical (not surgical) procedures available.
• No availability for all scheduled visits during the study.
• Any other circumstance under investigator´s opinion that prevents patient inclusion even though normal inclusion and exclusion criteria are met.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bone Marrow mesenchymal stem cell; Allogenic Bone Marrow mesenchymal stem cell in amniotic membrane transplant	Procedure: Stem Cell with Amniotic Membrane Transplant; Single stem cell expansion in amniotic membrane transplant
ACTIVE_COMPARATOR: Allogenic limbal stem cell Transplant; Stem Cell with Amniotic Membrane Transplant	Procedure: Stem Cell with Amniotic Membrane Transplant; Single stem cell expansion in amniotic membrane transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viability and safety of mesenchymal stem cell transplant	Absence of cell metaplasia with phenotype different to corneal or conjunctival as expected, confirmed by corneal impression cytology and in vivo confocal laser ophthalmoscopy	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absence of complications in pre and peri surgical implantation	Correct handling and implantation of stem cell with amniotic membrane transplant following an 4 step classification.	1 Week
Improvement of 2 lines in Best Corrected Visual Acuity	Improvement in visual acuity compared to baseline values before transplant	12 month

Collaborators and Investigators

• Sponsor: Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA
• Collaborators: University of Valladolid; Red de Terapia Celular; Centro en Red de Medicina Regenerativa de Castilla y Leon
• Investigators: Principal Investigator: Margarita Calonge, MD, PhD, Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA

Publications and helpful links

General Publications

• Calonge M, Perez I, Galindo S, Nieto-Miguel T, Lopez-Paniagua M, Fernandez I, Alberca M, Garcia-Sancho J, Sanchez A, Herreras JM. A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency. Transl Res. 2019 Apr;206:18-40. doi: 10.1016/j.trsl.2018.11.003. Epub 2018 Nov 22.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: March 22, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (ESTIMATE): March 23, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: stem cell transplant; cornea; limbus; insufficiency syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: IOBA-05-2010