Clinical trial NCT02012153: Mesenchymal Stromal Cells in Kidney Transplant Recipients
Official title: Autologous Mesenchymal Stromal Cells to Induce Tolerance in Living-donor Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Kidney Transplant Rejection
Keywords: Mesenchymal stromal cells
Kidney transplantation
Tolerance
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: A.O. Ospedale Papa Giovanni XXIII
First posted: 2013-12-16
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The general aim of the present study is to test a cell therapy with autologous ex-vivo expanded mesenchymal stromal cells (MSCs) as a strategy to induce tolerance in living-donor kidney transplant recipients. MSCs will be prepared accordingly to established protocols, starting from bone marrow explants of living-donor kidney transplant recipients obtained 3-4 months before kidney transplant. From these samples, MSCs will be expanded in Good Manufacturing Practice (GMP) approved facilities and used for the present study in patients undergoing kidney transplantation.


Eligibility criteria: Inclusion Criteria:

* Male and female patients;
* Aged 18 or older;
* Living-donor (related and unrelated, spouse/husband) kidney transplant recipients;
* Non-Human Leukocyte Antigen (HLA) identical with the donor (one or two haplotype mismatches);
* First kidney transplant;
* Capable of understanding the purpose and risk of the study;
* Written informed consent.

Exclusion Criteria:

* MSC donor positive for HIV-1, HIV-2, hepatitis B virus (HBV),hepatitis C virus (HCV), syphilis;
* 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 study protocol in the investigator's opinion.

Primary outcomes:
measure: Circulating naïve and memory T cell count (CD45RA/CD45RO) (flow cytometry analysis).
timeFrame: Changes from baseline at 6 and 12 months after transplant.
measure: T-cell function by ELISPOT assay in mixed lymphocyte reaction.
timeFrame: Changes from baseline at 6 and 12 months after transplant.
measure: Number of adverse events.
timeFrame: Changes from baseline up to 48 months.
measure: Circulating regulatory T cell count.
timeFrame: Changes from baseline at 6 and 12 months after transplant.
measure: Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR.
timeFrame: Changes from baseline at 6 and 12 months after transplant.
Secondary outcomes:
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: U.O. Nefrologia e Dialisi
Study officials:
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Giuseppe Remuzzi, MD
role: STUDY_CHAIR
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
name: Norberto Perico, MD
role: STUDY_DIRECTOR
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Giovanni Rota, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
name: Federica Casiraghi
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
References:
citation: Perico N, Casiraghi F, Todeschini M, Cortinovis M, Gotti E, Portalupi V, Mister M, Gaspari F, Villa A, Fiori S, Introna M, Longhi E, Remuzzi G. Long-Term Clinical and Immunological Profile of Kidney Transplant Patients Given Mesenchymal Stromal Cell Immunotherapy. Front Immunol. 2018 Jun 14;9:1359. doi: 10.3389/fimmu.2018.01359. eCollection 2018.