The Vienna Prograf and Endothelial Progenitor Cell Study
|First Received Date ICMJE||September 10, 2005|
|Last Updated Date||May 18, 2011|
|Start Date ICMJE||April 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00182559 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||The Vienna Prograf and Endothelial Progenitor Cell Study|
|Official Title ICMJE||The Vienna Prograf and Endothelial Progenitor Cell Study|
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.
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).
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Probability Sample|
Stable long-term kidney transplant recipients
|Condition ICMJE||Kidney Transplantation|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
|Publications *||Riegersperger M, Plischke M, Steiner S, Seidinger D, Sengoelge G, Winkelmayer WC, Sunder-Plassmann G. Effect of conversion from ciclosporin to tacrolimus on endothelial progenitor cells in stable long-term kidney transplant recipients. Transplantation. 2013 Jun 15;95(11):1338-45. doi: 10.1097/TP.0b013e31828fabb3.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||May 2009|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Patient has a functioning renal allograft and estimated GFR≥39 mL7min/1.73m2 within four weeks prior to study entry.
Patient has a stable graft function without biopsy proven acute rejection episode within 3 months prior to study entry.
Patient has not experienced a cardiovascular event. Patient has fully been informed and has given written informed consent according to ICH-GCP.
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.
Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.
|Ages||18 Years to 80 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Austria|
|NCT Number ICMJE||NCT00182559|
|Other Study ID Numbers ICMJE||2004-004209-98, 393/2004 Ethics Commitee Nr.|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Gere Sunder-Plassmann, Medical University Vienna|
|Study Sponsor ICMJE||Medical University of Vienna|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Medical University of Vienna|
|Verification Date||October 2004|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP