Rapamycin and Regulatory T Cells in Kidney Transplantation
Condition: Kidney Transplantation
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Cyclosporins; Rapamycin
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Neoral; Sirolimus; Rapamune
Intervention MeSH terms: Cyclosporine; Sirolimus; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immunosuppressive Agents; Immune system regulation; Regulatory T cells; Rapamycin; Tolerance