MSC and Kidney Transplant Tolerance (Phase A)

Monia Lorini22 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Renal Failure

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of adverse events

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

Time frame: Changes from baseline through study completion, up to 12 months after transplant.

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

Time frame: 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.

Time frame: 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.

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.

Time frame: Changes from baseline at 6 and 12 months after transplant.

Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR