Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of five infusions of characterized HLA-identical MSC in non immunosuppressed children with Osteogenesis Imperfecta (OI).

Detailed Description
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The principal aim of this trial is to assess the safety of non-mutated HLA-identical Mesenchymal stem cell (MSC) transplantation for OI pediatric patients irrespective of treatment with biphosphonates. Since MSC are inherently non-immunogenic and do not elicit proliferation of allogeneic lymphocytes (in co-culture experiments), a cell therapy based on HLA-identical or histocompatible (at least 5 shared out of 6 HLA antigens) allogenic MSC may be accomplished without subjecting the patients to immunosuppressor treatment. Adverse secondary effects due to immunosuppressor treatment will be avoided using this strategy thus patients may benefit from two cellular infusions. The patients will be followed for 2 years post their fifth and last MSC infusion.

Official Title
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Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Biological: Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age: older than 6 months and younger than 12 years old. Patients with molecular confirmation of mutation in either COL1A1 or COL1A2 genes associated with OI (type III). Patients with HLA identical (that shared at least 5/6 antigens) siblings willing to donate bone marrow-MSCs. All patients that fulfil the inclusion criteria regardless of whether or not they are undergoing biphosphonate treatment. Patients whose parents or the legal guardians are willing to sign the consent forms to participate in this clinical trial. Exclusion Criteria: Patient age: older than 12 years old Patients lacking confirmation of mutation in either COL1A1 or COL1A2 genes associated with severe deforming OI (type III). Other pathological subtypes of OI. Patients lacking of HLA identical (that shared at least 5/6 antigens) siblings willing to donate bone marrow-MSCs. Immunodeficiencies and any other malignancies. Participation in other clinical trial. Any medical or psychiatric condition that in the researcher´s opinion could affect the patient´s ability to complete the trial or hamper the participation in the trial. Patients whose parents or the legal guardians do not sign the consent forms

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells<br>Five Mesenchymal Stem Cell infusions | Biological: Mesenchymal Stem Cells<br>* Mesenchymal Stem Cell Infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events as a Measure of Safety |  | up to 2 years post last MSCs infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone mineral density |  | up to 2 years post last MSCs infusion | 
| fracture rate |  | up to 2 years post last MSCs infusion | 
| growth velocity |  | up to 2 years post last MSCs infusion | 
| change from baseline in degree of functionality | 9 question survey using a Bleck functional scale | up to 2 years post last MSCs infusion | 
| change from baseline in well-being | A 20 item questionnaire designed to evaluate the well-being will be used | up to 2 years post last MSCs infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cell based therapy, cell infusion