Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

— TERCELOI  

Official title:

Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172885
• Other study ID #: EudraCT Number:2012-002553-38
• Secondary ID: Health Departmen
• Status: Completed
• Phase: Phase 1
• Start date: April 2014
• Est. completion date: December 2018

Study information

• Verified date: September 2023
• Source: Hospital de Cruces
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Biological:
• Mesenchymal Stem Cells
Mesenchymal Stem Cell Infusions

Locations

Country	Name	City	State
Spain	Hospital Universitario Cruces	Barakaldo	Bizkaia
Spain	Hospital Universitario Getafe	Getafe	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Hospital de Cruces	Hospital Infantil Universitario Niño Jesús, Madrid, Spain, Hospital Universitario Getafe

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events as a Measure of Safety		up to 2 years post last MSCs infusion
Secondary	bone mineral density		up to 2 years post last MSCs infusion
Secondary	fracture rate		up to 2 years post last MSCs infusion
Secondary	growth velocity		up to 2 years post last MSCs infusion
Secondary	change from baseline in degree of functionality	9 question survey using a Bleck functional scale	up to 2 years post last MSCs infusion
Secondary	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

External Links

•   Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial