Rapamycin and Regulatory T Cells in Kidney Transplantation

NCT ID: NCT01014234

Last Updated: 2015-03-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2013-06-30

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:

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.

Conditions

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Kidney Transplantation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rapamycin

Maintenance treatment with rapamycin + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.

Group Type EXPERIMENTAL

Rapamycin

Intervention Type DRUG

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.

cyclosporine

Maintenance treatment with cyclosporine + mycophenolate + prednisone. This treatment will be introduced one month after renal transplantation.

Group Type ACTIVE_COMPARATOR

Cyclosporins

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Neoral Sirolimus Rapamune

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role lead

Responsible Party

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Carmelo Libetta

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antonio Dal Canton, MD

Role: PRINCIPAL_INVESTIGATOR

Policlinico Fondazione IRCCS "San Matteo", Pavia

Locations

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Policlinico Fondazione IRCCS "San Matteo"

Pavia, , Italy

Site Status

Countries

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Italy

References

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Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG. Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol. 2006 Dec 15;177(12):8338-47. doi: 10.4049/jimmunol.177.12.8338.

Reference Type BACKGROUND
PMID: 17142730 (View on PubMed)

San Segundo D, Fernandez-Fresnedo G, Ruiz JC, Rodrigo E, Benito MJ, Arias M, Lopez-Hoyos M. Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients. Clin Transplant. 2010 May-Jun;24(3):386-93. doi: 10.1111/j.1399-0012.2009.01086.x. Epub 2009 Sep 11.

Reference Type BACKGROUND
PMID: 19744094 (View on PubMed)

Ramirez E, Morales JM, Lora D, Mellado M, Cevey M, Alfaro FJ, De Pablos P, Andres A, Paz-Artal E, Serrano A. Peripheral blood regulatory T cells in long-term kidney transplant recipients. Transplant Proc. 2009 Jul-Aug;41(6):2360-2. doi: 10.1016/j.transproceed.2009.05.007.

Reference Type BACKGROUND
PMID: 19715919 (View on PubMed)

Other Identifiers

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20070034809

Identifier Type: -

Identifier Source: org_study_id

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