Clinical trial NCT02565459: MSC and Kidney Transplant Tolerance (Phase A)
Official title: Third-party Bone Marrow-derived Mesenchymal Stromal Cells to Induce Tolerance in Recipients of Kidney Transplants From Deceased Donors (Phase A)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Chronic Renal Failure
Keywords: Mesenchymal stromal cells
kidney transplantation
tolerance
Lead sponsor: A.O. Ospedale Papa Giovanni XXIII
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2015-10-01
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 ex-vivo expanded bone marrow-derived mesenchymal stromal cells (MSCs) as a strategy to induce tolerance in kidney transplant recipients with a deceased donor. MSCs will be prepared accordingly to established protocols, starting from the remnants in the bag and filter at the end of the bone marrow infusions. 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.

The proposed study will be developed in two phases: i) a pilot explorative safety/biologic-mechanistic phase (Phase A), ii) a pilot efficacy phase (Phase B).


Eligibility criteria: Inclusion Criteria:

* First single kidney transplant;
* Capable of understanding the purpose and risk of the study;
* Written informed consent.

Exclusion Criteria:

* PRA \>10%;
* Specific contraindication to MSC infusion;
* Any clinical relevant condition that might affect study participation and/or study results;
* Childbearing potential without effective contraception;
* Pregnant women and nursing mothers;
* Unwillingness or inability to follow study protocol in the investigator's opinion.

Primary outcomes:
measure: Number of adverse events
timeFrame: Changes from baseline through study completion, up to 12 months after transplant.
measure: Circulating naive and memory T cell count (CD45RA/CD45RO) (flow cytometry analysis)
timeFrame: Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant.
measure: Circulating regulatory T cell count.
timeFrame: Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant.
measure: T-cell function in mixed lymphocyte reaction.
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: