Rapamycin and Regulatory T Cells in Kidney Transplantation

This study is currently recruiting participants.
Verified July 2012 by IRCCS Policlinico S. Matteo
Sponsor:
Information provided by (Responsible Party):
Carmelo Libetta, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:
NCT01014234
First received: November 13, 2009
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Kidney Transplantation
Drug: Cyclosporins
Drug: Rapamycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rapamycin and Regulatory T Cells in Renal Transplant Patients: a Two-year Randomized Prospective Study

Resource links provided by NLM:


Further study details as provided by IRCCS Policlinico S. Matteo:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 56
Study Start Date: July 2008
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Neoral

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01014234

Contacts
Contact: Carmelo Libetta, MD 0039-0382-501813 clibetta@smatteo.pv.it

Locations
Italy
Policlinico Fondazione IRCCS "San Matteo" Recruiting
Pavia, Italy, 27100
Contact: Antonio Dal Canton, MD    0039-0382-502590    dalcanton@smatteo.pv.it   
Principal Investigator: Antonio Dal Canton, MD         
Sub-Investigator: Carmelo Libetta, MD         
Sub-Investigator: Valentina Portalupi, MD         
Sub-Investigator: Pasquale Esposito, MD         
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
Investigators
Principal Investigator: Antonio Dal Canton, MD Policlinico Fondazione IRCCS "San Matteo", Pavia
  More Information

Publications:
Responsible Party: Carmelo Libetta, MD, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT01014234     History of Changes
Other Study ID Numbers: 20070034809
Study First Received: November 13, 2009
Last Updated: July 6, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS Policlinico S. Matteo:
Immunosuppressive Agents
Immune system regulation
Regulatory T cells
Rapamycin
Tolerance

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Sirolimus
Everolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014