Clinical trial NCT02260375: MSC Therapy in Liver Transplantation
Official title: THIRD-PARTY BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS TO INDUCE TOLERANCE IN LIVER TRANSPLANT RECIPIENTS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Liver Transplant Rejection
Keywords: Mesenchymal stromal cells; liver transplantation; tolerance.
Lead sponsor: A.O. Ospedale Papa Giovanni XXIII
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2014-10-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The general aim of the present study is to test a cell therapy with third-party allogeneic ex-vivo expanded MSCs as a strategy to induce tolerance in liver transplant recipients. MSCs will be prepared accordingly to established protocols , starting from diagnostic samples of bone marrow aspirates (2-5 mL) or using the remnants in the bag and filter at the end of the bone marrow infusions. From these samples, MSCs will be expanded in GMP approved facilities and used for the present study in patients undergoing liver transplantation.


Eligibility criteria: Inclusion Criteria:

For this study, the following inclusion criteria should be fulfilled before starting withdrawal of drugs after 1 year post-transplant:

* First liver transplant
* Capable of understanding the purpose and risk of the study
* Written informed consent

Exclusion Criteria:

* Specific contraindication to MSC infusion
* Any clinical relevant condition that might affect study participation and/or study results
* Pregnant women and nursing mothers
* Unwillingness or inability to follow the study protocol in the investigator's opinion.

Primary outcomes:
measure: Number of adverse events
timeFrame: Changes from baseline up to 120 month.
measure: Liver tissue mRNA level of Transferrin receptor CD71 (TFRC) and Hepcidin antimicrobial peptide (HAMP) genes
timeFrame: At 12 and 60 month.
measure: Circulating naive and memory T cell conts (CD45RA/CD45RO)(flow cytometry analysis)
timeFrame: Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.
measure: T-cell function in mixed lymphocyte reaction
timeFrame: Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month.
Secondary outcomes:
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: U.S.C Nefrologia e Dialisi
city: Bergamo
country: Italy
facility: USC Chirurgia Generale III
city: Bergamo
country: Italy
facility: USC Ematologia
city: Bergamo
country: Italy
facility: USC Gastroenterologia
city: Bologna
country: Italy
facility: Servizio di Immunoematologia e Medicina Trasfusionale
city: Bologna
country: Italy
facility: Unità Chirurgia Generale e Trapianti
Study officials:
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Giuseppe Remuzzi, MD
role: STUDY_CHAIR
affiliation: IRCCS-Istituto di Ricerche Farmacologiche M. Negri
name: Norberto Perico, MD
role: STUDY_DIRECTOR
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Michele Colledan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Stefano Fagiuoli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laboratorio G.Lanzani, Bergamo, Italy
name: Martino Introna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Alessandro Rambaldi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico S. Orsola Bologna, Italy
name: Antonio Pinna, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico S. Orsola Bologna, Italy
name: Claudio Velati, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Casiraghi F, Perico N, Podesta MA, Todeschini M, Zambelli M, Colledan M, Camagni S, Fagiuoli S, Pinna AD, Cescon M, Bertuzzo V, Maroni L, Introna M, Capelli C, Golay JT, Buzzi M, Mister M, Ordonez PYR, Breno M, Mele C, Villa A, Remuzzi G; MSC-LIVER Study Group. Third-party bone marrow-derived mesenchymal stromal cell infusion before liver transplantation: A randomized controlled trial. Am J Transplant. 2021 Aug;21(8):2795-2809. doi: 10.1111/ajt.16468. Epub 2021 Feb 22.