Osteogenesis imperfecta (OI) is a rare genetic disorder with increased bone fragility of varying severity. In the majority of patients the disease is caused by mutations in collagen type I. Severe OI is characterized by osteopenia, frequent fractures, progressive deformity, short stature, loss of mobility, chronic pain and can lead to premature death. At present a cure does not exist.
Conditions
Interventions
Product Name: celulas madre mesenquimales troncales adultas alogenicas de médula ósea no expandida
Product Code: REF CRUZADA PEI Nº 12-088
Pharmaceutical Form: Living tissue equivalent
INN or Proposed
Sponsors
Itziar Astigarraga Aguirre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.-Patient age: older than 6 months and younger than 12 years old. 2.-Patients with molecular confirmation of mutation in either COL1A1 or COL1A2 genes associated with severe deforming OI (type III). 3.-Patiens with HLA identical (that shared at least 5/6 antigens) siblings willing to donate bone marrow-MSCs. 4.-All patients that fulfil the inclusion criteria regardless of whether or not they are undergoing biphosphonate treatment 5.-Patients whose parents or the legal guardians are willing to sign the consent forms to participate in this clinical trial. Are the trial subjects under 18? yes Number of subjects for this age range: 3 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.-Patient age: older than 12 years old 2.-Patients lacking confirmation of mutation in either COL1A1 or COL1A2 genes associated with severe deforming OI (type III). 3.-Other pathological subtypes of OI. 4.-Patiens lacking of HLA identical (that shared at least 5/6 antigens) siblings willing to donate bone marrow-MSCs. 5.-Immunodeficiencies and any other malignancies 6.-Participation in other clinical trial 7.-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. 8.-Patients whose parents or the legal guardians do not sign the consent forms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the safety of the stem cell transplantation process using characterized HLA-identical MSC in OI infants already subjected to pamidronate treatment, but who are not receiving immunosuppresion treatment;Secondary Objective: To demonstrate the efficacy of the MSCs procedure, to verify that treatment of OI patients with several HLA-identical MSC injections, is not only a safe procedure (primary objective), but will increase the benefits observed with only one HLA-identical MSC injection;Primary end point(s): The principal aim of this project is to assess the safety of non-mutated HLA-identical MSC transplantation for OI pediatric patients irrespective of treatment with pamidronate. 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 allogenic MSC or that they shared at least 5 out of 6 HLA antigens it could be accomplished without subjecting the patients to immunosupressor treatment. Adverse secondary effects due to immunosopressor treatment could be avoided using this strategy and patients may reap the benefits of two cellular infusions instead of one. The beneficial effects observed in patients subjected to cell therapy seem to last for approximately six months after the infusion. In addition to clinical and analytical analysis of blood and urine tests, the immune responses of treated patients will be evaluated. Humoral and cell-mediated responses will be determined.;Timepoint(s) of evaluation of this end point: The clinical and analytical evaluations as well as immune response evaluation will take place in the initial visit (before the cell infusion which will be visit 1) to establish baselines and at the following intervals: .-visit 2, 7 days post-first infusion .-visit 3, 28 days post-first infusion .-visit 4, 4 months post-first infusion .-visit 5, 5 months post-first infusion, second infusion .-visit 6, 7 days post-second | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary end point is to demonstrate the efficacy of MSC transplantation for OI patients. The evaluation of treatment efficacy will be based on physical and clinical evaluation, analytical and radiological parameters associated with bone metabolism, reduction in the frequencies of bone fracture, increase in growth velocity, positive impact in functionality and an improvement in well being.;Timepoint(s) of evaluation of this end point: The clinical and analytical evaluations will take place in the initial visit (before the cell infusion on visit 1) and at the following visits: .-visit 2, 7 days post-first infusion .-visit 3, 28 days post-first infusion .-visit 4, 4 months post-first infusion .-visit 5, 5 months post-first infusion, second infusion .-visit 6, 7 days post-second infusion .-visit 7, 28 days post-second infusion .-visit 8, 9 months post-first infusion The radiological tests only will be performed at the initial and last visits. | — |
Countries
Spain
Contacts
Public ContactU. EPIDEMIOLOGIA CLINICA- APOYO INV
HOSPITAL UNIVERSITARIO CRUCES
Outcome results
None listed