Rapamycin and Regulatory T Cells in Kidney Transplantation

NCT01014234 | Completed Phase 2 DMC

• 1 other identifier: 20070034809
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Transplantation

Keywords

Immunosuppressive Agents; Immune system regulation; Regulatory T cells; Rapamycin; Tolerance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

Rapamycin

EXPERIMENTAL

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

Drug: Rapamycin

cyclosporine

ACTIVE COMPARATOR

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

Drug: Cyclosporins

Interventions

Cyclosporins 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.

Also known as: Neoral

cyclosporine

Rapamycin 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.

Also known as: Sirolimus, Rapamune

Rapamycin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female aged from 18 to 75 years
• Transplanted patients from cadaveric donors
• Patients who has given written informed consensus

You may not qualify if:

• Legally unable patients
• Patients who have been participated to others studies in the last 3 months
• Addicted to alcohol or smoking

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Policlinico Fondazione IRCCS "San Matteo"

Pavia, 27100, Italy

Location

Related 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. doi: 10.4049/jimmunol.177.12.8338.

  PMID: 17142730 BACKGROUND

• 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.

  PMID: 19744094 BACKGROUND

• 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.

  PMID: 19715919 BACKGROUND

MeSH Terms

Interventions

Cyclosporins; Cyclosporine; Sirolimus

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals

Study Officials

• Antonio Dal Canton, MD

  Policlinico Fondazione IRCCS "San Matteo", Pavia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 16, 2009
• Study Start: July 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: March 25, 2015

Record last verified: 2015-03

Locations

IT (1)