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Sponsored by: |
Medical University of Vienna |
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Information provided by: | Medical University of Vienna |
ClinicalTrials.gov Identifier: | NCT00182559 |
The aim of the study is to determine if the conversion from the immunosuppressive agent cyclosporine to tacrolimus contributes to an improvement of the cardiovascular risk factors, better kidney function and immune system.
Study Type: | Observational |
Study Design: | Prospective |
Official Title: | The Vienna Prograf and Endothelial Progenitor Cell Study |
Estimated Enrollment: | 148 |
Study Start Date: | April 2004 |
Estimated Study Completion Date: | May 2009 |
In addition to hypertension, diabetes, hyperlipidemia and smoking, as well as other non-traditional risk factors such as elevated C-reactive protein, homocysteine, Lp(a), or reduced renal function, depletion of endothelial progenitor cells (EPC) in the peripheral circulation may represent another important explanation for the excess cardiovascular morbidity of kidney transplant recipients. In this context, the potential association of immunosuppressive therapy with EPCs in kidney transplant recipients deserves special consideration. The use of tacrolimus associated with a more favorable cardiovascular risk factors profile in terms of improved blood pressure and lipid levels in kidney transplant recipients compared to cyclosporine users. Therefore, one can speculate whether tacrolimus users might have greater EPC counts compared to patients treated with cyclosporine.
In a pilot study we cross-sectionally studied EPC counts in 90 stable, middle-aged kidney transplant recipients.
From multivariate analyses, we found a independent inverse association between EPC counts and body mass index and systolic blood pressure. Statin use was associated with greater EPC counts, while patients receiving azathioprine had lower EPC counts. These findings raised the hypothesis whether EPCs are responsible, at least in part, for the well-established association between these factors and cardiovascular outcomes.
Cystatin C is superior to serum creatinine as a marker of kidney function since cystatin C is a more sensitive marker than serum creatine for small changes in GFR. Until now, there are no available data on the change of cystatin C as a measure of graft function after conversion of a cyclosporine based immunosuppressive regimen to tacrolimus. There is accumulating evidence for an important pathogenetic role of donor-reactive antibodies in kidney allograft rejection. Recent studies suggest an anti-humoral activity of tacrolimus in the setting of chronic rejection. Recent findings suggest that in patients who are on cyclosporine, tacrolimus rescue therapy could efficiently inhibit antibody formation. Objective 1: To evaluate the change in endothelial Progenitor cell (EPC) count in kidney graft recipients converted from cyclosporine to tacrolimus. Objective 2: To evaluate the change in cystatin C as a measure of renal function in kidney graft recipients converted from cyclosporine to tacrolimus. Objective 3: To determine the effect of tacrolimus on humoral alloreactivity in kidney graft recipients Study design: A 2:1 randomized, parallel group, open-label, prospective trial comparing two different immunosuppressive regimens in approximately 148 patients. Group A: Convert to tacrolimus in combination with/without MMF and/or steroids. Group B: Maintain cyclosporine in combination with/without MMF and/or steroids.
Patients will be followed up for 24 months after conversion.
In an amendment (August 2006) we registered pharmacogenetical analyses of the multi-drug resistance transporter 1 (MDR1) gene (gene symbol: ABCB1). The patients´ DNA is extracted from peripheral venous blood using the QIAamp DSP DNA Blood Mini Kit (Qiagen). Two ABCB1 gene sections are amplified by polymerase chain reaction (PCR).
Mutations are determined by restriction enzymes (restriction fragment length polymorphisms, RFLP).
Ages Eligible for Study: | 18 Years to 80 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Females are not pregnant and agree to practice effective birth control while receiving immunosuppressant medication. Patient has indications for conversion at the investigators discretion or is suffering from cyclosporine associated side effects like hypertension, hyperlipidemia or cosmetic side effects.
Exclusion Criteria:
Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.
Study ID Numbers: | 2004-004209-98, 393/2004 Ethics Commitee Nr. |
Study First Received: | September 10, 2005 |
Last Updated: | March 17, 2008 |
ClinicalTrials.gov Identifier: | NCT00182559 History of Changes |
Health Authority: | Austria: Federal Ministry for Health and Women |
kidney transplantation tacrolimus cyclosporine conversion |
Cyclosporine Tacrolimus Cyclosporins |