Chronic Renal Failure
Conditions
Keywords
Mesenchymal stromal cells, kidney transplantation, tolerance
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).
Interventions
BIOLOGICALMesenchymal Stromal Cells
Sponsors
Mario Negri Institute for Pharmacological Research
Monia Lorini
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events | Changes from baseline through study completion, up to 12 months after transplant. | At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded. |
| Circulating naive and memory T cell count (CD45RA/CD45RO) (flow cytometry analysis) | Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant. | — |
| Circulating regulatory T cell count. | Changes from baseline at 7, 14, 30 days after transplant and then every six months through study completion, up to 12 months after transplant. | — |
| T-cell function in mixed lymphocyte reaction. | Changes from baseline at 6 and 12 months after transplant. | IFNg-producing T cells (spots/300.000 cells) and CD8+ T cell-mediated cytotoxicity (percentage of specific lysis) will be measured in mixed lymphocyte reaction. |
| Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR | Changes from baseline at 6 and 12 months after transplant. | — |
Countries
Italy
Contacts
Primary ContactNorberto Perico, MD
Outcome results
None listed