NCT02260375

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2014

Longer than P75 for phase_1

Geographic Reach
1 country

6 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2014

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

October 6, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 9, 2014

Completed
10 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2025

Completed
Last Updated

April 6, 2018

Status Verified

April 1, 2018

Enrollment Period

10 years

First QC Date

October 6, 2014

Last Update Submit

April 5, 2018

Conditions

Liver Transplant Rejection

Keywords

Mesenchymal stromal cells; liver transplantation; tolerance.

Outcome Measures

Primary Outcomes (4)

  • Number of adverse events

    At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded.

    Changes from baseline up to 120 month.

  • Liver tissue mRNA level of Transferrin receptor CD71 (TFRC) and Hepcidin antimicrobial peptide (HAMP) genes

    At 12 and 60 month.

  • Circulating naive and memory T cell conts (CD45RA/CD45RO)(flow cytometry analysis)

    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.

  • T-cell function in mixed lymphocyte reaction

    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.

Study Arms (2)

Mesenchymal Stromal Cells (MSC)

EXPERIMENTAL

A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party MSC (from healthy donors) will be performed in patients assigned to the MSC procedure in addition to the liver transplantation.

Biological: Mesenchymal Stromal Cells

No treatment.

NO INTERVENTION

Interventions

Mesenchymal Stromal CellsBIOLOGICAL
Mesenchymal Stromal Cells (MSC)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

U.S.C Nefrologia e Dialisi

Bergamo, 24127, Italy

RECRUITING

USC Chirurgia Generale III

Bergamo, 24127, Italy

RECRUITING

USC Ematologia

Bergamo, 24127, Italy

RECRUITING

USC Gastroenterologia

Bergamo, 24127, Italy

RECRUITING

Servizio di Immunoematologia e Medicina Trasfusionale

Bologna, 40138, Italy

RECRUITING

Unità Chirurgia Generale e Trapianti

Bologna, 40138, Italy

RECRUITING

Related Publications (1)

  • 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.

    PMID: 33370477DERIVED

Study Officials

  • Giuseppe Remuzzi, MD

    A.O. Ospedale Papa Giovanni XXIII

    STUDY CHAIR

  • Norberto Perico, MD

    IRCCS-Istituto di Ricerche Farmacologiche M. Negri

    STUDY DIRECTOR

  • Michele Colledan, MD

    A.O. Ospedale Papa Giovanni XXIII

    PRINCIPAL INVESTIGATOR

  • Stefano Fagiuoli, MD

    A.O. Ospedale Papa Giovanni XXIII

    PRINCIPAL INVESTIGATOR

  • Martino Introna, MD

    Laboratorio G.Lanzani, Bergamo, Italy

    PRINCIPAL INVESTIGATOR

  • Alessandro Rambaldi, MD

    A.O. Ospedale Papa Giovanni XXIII

    PRINCIPAL INVESTIGATOR

  • Antonio Pinna, MD

    Policlinico S. Orsola Bologna, Italy

    PRINCIPAL INVESTIGATOR

  • Claudio Velati, MD

    Policlinico S. Orsola Bologna, Italy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Remuzzi, MD

CONTACT

0039 0352674037gremuzzi@hpg23.it

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
EC Secretary

Study Record Dates

First Submitted

October 6, 2014

First Posted

October 9, 2014

Study Start

October 1, 2014

Primary Completion

October 1, 2024

Study Completion

October 1, 2025

Last Updated

April 6, 2018

Record last verified: 2018-04

Locations

IT(6)