MSC and Kidney Transplant Tolerance (Phase A)
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Mesenchymal Stromal Cells (MSC) A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party (from healthy donors) MSCs will be performed in patients randomized to the MSC procedure in addition to the kidney transplantation. |
Biological: Mesenchymal Stromal Cells
|
| No Intervention: No intervention
|
Outcome Measures
Primary Outcome Measures
- 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.]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | U.O. Nefrologia e Dialisi | Bergamo | Italy | 24127 |
Sponsors and Collaborators
- Monia Lorini
- Mario Negri Institute for Pharmacological Research
Investigators
- Study Chair: Giuseppe Remuzzi, MD, A.O. Ospedale Papa Giovanni XXIII
- Study Director: Norberto Perico, MD, Istituto Di Ricerche Farmacologiche Mario Negri
- Principal Investigator: Giovanni Rota, MD, A.O. Ospedale Papa Giovanni XXIII
- Principal Investigator: Federica Casiraghi, Istituto Di Ricerche Farmacologiche Mario Negri
- Principal Investigator: Martino Introna, MD, Laboratorio G. Lanzani, Bergamo, Italy
- Principal Investigator: Alessandro Rambaldi, MD, A.O. Ospedale Papa Giovanni XXIII
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Third-party MSC-Tx tolerance A
- 2015-002186-27