Rapamycin and Regulatory T Cells in Kidney Transplantation

Study Overview
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Brief Summary
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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
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It is two years randomised controlled trial in parallel groups. It has been resolved to compare different immunosuppressive regimens: cyclosporine+ mycophenolate+prednisone 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.

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

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Cyclosporins
* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin<br>Maintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. | Drug: Rapamycin<br>* 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.<br>* Other names: Rapamune;|
| Active Comparator: cyclosporine<br>Maintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation. | Drug: Cyclosporins<br>* 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.<br>* Other names: Neoral;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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. |  | Every two months during the follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppressive Agents, Immune system regulation, Regulatory T cells, Rapamycin, Tolerance