Trascriptomic differences between tacrolimus and mTOR inhibitors in the immunosuppressive treatment of renal transplantatio

• Conditions: Renal Transplantation; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2013-004538-14-IT
• Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-02-19
• Last Update Posted: 9 March 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Written informed consent
• age > 18 years
• first renal transplantation
• renal transplantation performed since more than 6 months at the time of enrollment
• estimated GFR (as assessed by the use of the equation aMDRD) greater than 30 mL / min
• Chronic treatment with tacrolimus or mTOR inhibitors (everolimus, sirolimus) in
combination with mycophenolate mofetil (MMF) since more than 6 months
• Blood levels between 4-8 ng/ml (Tacrolimus) and 4-8 ug/L (inhibitors
mTOR).
• Chronic treatment with corticosteroid (prednisone 5 mg or 4 mg of methylprednisolone)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

• Patients participating in another study
• Change in GFR> 30% in the 6 months prior to enrollment
• Diagnosis and treatment of acute rejection in the 6 months prior to enrollment
• other solid organ transplantation in combination with renal transplantation
• Malignant neoplasm in the active phase (excluding non-melanoma skin cancer)
•Hemodialysis
• Severe acute and chronic liver disease (hepatitis B virus-related, hepatitis C virus-related, toxic,
immunoallergic)
• Women with a positive pregnancy test at enrollment
Pregnant or breastfeeding women or women not using effective contraception if
they are of childbearing age.
• planned surgery during the study period (with the exception of an cataract surgery, vascular surgery, removal of urethral stent, tube replacement
nephrostomy, minor surgery in an outpatient surgery that does not require
hospitalization)
• HIV infection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To understand the molecular basis of the mechanism of action of tacrolimus comparing the trascriptomic profile in peripheral blood mononuclear cells of patients chronically treated with FK506 and treated with mTOR inhibitors (sirolimus or everolimus).<br>;Secondary Objective: To identify differences between biomolecular inhibitors of calcineurin and mTOR in the cells of the immune system (LMP).<br>;Primary end point(s): For each of the 22 283 probes: the level of expression (standardized) hybridized mRNA detected by microarray technology<br>;Timepoint(s) of evaluation of this end point: baseline<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Validation and confirmation of the genes differentially expressed after microarray analysis in the two study groups through real time polymerase chain reaction technique.<br>- Confirmation of the difference of selected genes from the microarray analysis through evaluation of their protein level by Western blotting technique<br><br>;Timepoint(s) of evaluation of this end point: Baseline