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

November 13, 2009
July 6, 2012
July 2008
March 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01014234 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Rapamycin and Regulatory T Cells in Kidney Transplantation
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Kidney 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
  • 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
  • Experimental: Rapamycin
    Maintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.
    Intervention: Drug: Rapamycin
  • Active Comparator: cyclosporine
    Maintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.
    Intervention: Drug: Cyclosporins

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
56
March 2013
March 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact: Carmelo Libetta, MD 0039-0382-501813 clibetta@smatteo.pv.it
Italy
 
NCT01014234
20070034809
Yes
Carmelo Libetta, IRCCS Policlinico S. Matteo
IRCCS Policlinico S. Matteo
Not Provided
Principal Investigator: Antonio Dal Canton, MD Policlinico Fondazione IRCCS "San Matteo", Pavia
IRCCS Policlinico S. Matteo
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP