Rapamycin and Regulatory T Cells in Kidney Transplantation

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01014234
• Other study ID #: 20070034809
• Status: Completed
• Phase: Phase 2
• First received: November 13, 2009
• Last updated: March 24, 2015
• Start date: July 2008
• Est. completion date: June 2013

Study information

• Verified date: March 2015
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Policlinico Fondazione IRCCS "San Matteo"	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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. — View Citation

Ramírez E, Morales JM, Lora D, Mellado M, Cevey M, Alfaro FJ, De Pablos P, Andrés 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. — View Citation

San Segundo D, Fernández-Fresnedo G, Ruiz JC, Rodrigo E, Benito MJ, Arias M, López-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes