MSC and Kidney Transplant Tolerance (Phase A)

Third-party Bone Marrow-derived Mesenchymal Stromal Cells to Induce Tolerance in Recipients of Kidney Transplants From Deceased Donors (Phase A)

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 Overview

• Status: Unknown
• Conditions: Chronic Renal Failure
• Intervention / Treatment: Biological: Mesenchymal Stromal Cells

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • U.O. Nefrologia e Dialisi
    • Contact: Piero Ruggenenti, MD; Phone Number: 0039 035 2674037; Email: pruggenenti@hpg23.it
    • Sub-Investigator: Eliana Gotti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervention
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded.	Changes from baseline through study completion, up to 12 months after transplant.
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.	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.	Changes from baseline at 6 and 12 months after transplant.
Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR		Changes from baseline at 6 and 12 months after transplant.

Collaborators and Investigators

• Sponsor: Monia Lorini
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 24, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 6, 2018
• Last Update Submitted That Met QC Criteria: April 5, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: kidney transplantation; tolerance; Mesenchymal stromal cells
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: Third-party MSC-Tx tolerance A; 2015-002186-27 (EudraCT Number)