Rapamycin and Regulatory T Cells in Kidney Transplantation

March 24, 2015 updated by: Carmelo Libetta, IRCCS Policlinico S. Matteo

Rapamycin and Regulatory T Cells in Renal Transplant Patients: a Two-year Randomized Prospective Study

The immune system response is mediated by the interaction between the antigen presenting cell (APC), CD4+ T helper cells (Th) and CD4+ CD25+ regulatory T cells, a subgroup of CD4+ T cell which express IL-2 receptor (CD25) and the transcriptional factor foxp3. Regulatory T cell may contribute to the maintenance of tolerance by suppressing the immune response to normal or tumor associated antigens.

Regulatory T cell emerge from the thymus during ontogenesis and they represent about 10 % of the peripheral Cd4+ t cells.

Rapamycin is one the most use treatment to prevent renal allograft failure. Differently from calcineurin inhibitors (cyclosporine and tacrolimus), that inhibit T-cell activation through the inhibition of calcineurin activation, rapamycin inhibits cellular proliferation by impairing the progression of the cellular cycle, in particular by interaction with mTOR. Recently Battaglia et al. have demonstrated a Treg amplification in murine CD4+ lymphocytes treated with rapamycin in vitro.

Aim of the study is to evaluate the effect of different immunosuppressive regimens on regulatory T cell and to verify the hypothesis that rapamycin may induce tolerance in kidney transplanted patients, more than cyclosporine treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

It is two years randomised controlled trial in parallel groups.

It has been resolved to compare different immunosuppressive regimens:

  1. cyclosporine+ mycophenolate+prednisone
  2. rapamycin + mycophenolate + prednisone, this treatment should be introduced after one month from renal transplantation.

Patient should visited at month 1-6-12-24 from the transplant. During the control we will reported the following data: physical examination, blood test (blood count, creatinin, BUN, immunosuppressive blood concentration, histological response of surveillance renal biopsy), blood pressure, attendant change of current therapy, pathological variation, or any hospitalisation both ordinary or in DH regimen.

Moreover in all control visit it will be collected a blood sample for evaluation of regulatory t cells.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Policlinico Fondazione IRCCS "San Matteo"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Male and female aged from 18 to 75 years
  • Transplanted patients from cadaveric donors
  • Patients who has given written informed consensus

Exclusion Criteria:

  • Legally unable patients
  • Patients who have been participated to others studies in the last 3 months
  • Addicted to alcohol or smoking

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rapamycin
Maintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.
Drug: Rapamycin
These patients will undergo maintenance immunosuppressive treatment with rapamycin + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary.
Other Names:
  • Sirolimus
  • Rapamune
Active Comparator: cyclosporine
Maintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.
Drug: Cyclosporins
These patients will undergo maintenance immunosuppressive treatment with cyclosporine + mycophenolate + prednisone according to established clinical practice. The dosage of drugs will be based on evaluations of serum trough levels and it will be adjusted when necessary.
Other Names:
  • Neoral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The absolute number of T-reg after renal transplant in patients in treatment with rapamycin compared to patients treated with cyclosporine
Time Frame: Every 6 months after the transplantation
Every 6 months after the transplantation

Secondary Outcome Measures

Outcome Measure
Time Frame
Adverse events developed during the duration of the clinical study, that damage the patient, that is not part of the natural history of the disease.
Time Frame: Every two months during the follow-up
Every two months during the follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Policlinico S. Matteo

Investigators

  • Principal Investigator: Antonio Dal Canton, MD, Policlinico Fondazione IRCCS "San Matteo", Pavia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

November 13, 2009

First Submitted That Met QC Criteria

November 13, 2009

First Posted (Estimate)

November 16, 2009

Study Record Updates

Last Update Posted (Estimate)

March 25, 2015

Last Update Submitted That Met QC Criteria

March 24, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070034809

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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