Clinical trial NCT02172885: Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
Official title: Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteogenesis Imperfecta
Keywords: Mesenchymal stem cell based therapy
cell infusion
Lead sponsor: Hospital de Cruces
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Getafe
name: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
First posted: 2014-06-24
Enrollment: 2
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events as a Measure of Safety
timeFrame: up to 2 years post last MSCs infusion
Secondary outcomes:
measure: bone mineral density
timeFrame: up to 2 years post last MSCs infusion
measure: fracture rate
timeFrame: up to 2 years post last MSCs infusion
measure: growth velocity
timeFrame: up to 2 years post last MSCs infusion
measure: change from baseline in degree of functionality
timeFrame: up to 2 years post last MSCs infusion
measure: change from baseline in well-being
timeFrame: up to 2 years post last MSCs infusion
Other outcomes:
Locations:
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Bizkaia
city: Getafe
country: Spain
facility: Hospital Universitario Getafe
state: Madrid
Study officials:
affiliation: BioCruces Health Research Institute/Cruces University Hospital
name: Clara I. Rodríguez, Ph. D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Infante A, Gener B, Vazquez M, Olivares N, Arrieta A, Grau G, Llano I, Madero L, Bueno AM, Sagastizabal B, Gerovska D, Arauzo-Bravo MJ, Astigarraga I, Rodriguez CI. Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial. Clin Transl Med. 2021 Jan;11(1):e265. doi: 10.1002/ctm2.265.
citation: Infante A, Cabodevilla L, Gener B, Rodriguez CI. Circulating TGF-beta Pathway in Osteogenesis Imperfecta Pediatric Patients Subjected to MSCs-Based Cell Therapy. Front Cell Dev Biol. 2022 Feb 9;10:830928. doi: 10.3389/fcell.2022.830928. eCollection 2022.