The Vienna Prograf and Endothelial Progenitor Cell Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Change in endothelial progenitor cells from baseline to month 24
研究概览
简要总结
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.
详细描述
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 glomerular filtration rate. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is recipient of a deceased or living donor renal transplant (including retransplants) Patient is 18 years or age or older at the time of transplantation. Patient is at least 6 months post-transplant. Patient is on a cyclosporine-based immunosuppression regimen o combination with/without mycophenolate mofetil and/or steroids at study entry.
- •Patient has a functioning renal allograft and estimated GFR≥39 mL/min/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 the International Conference on Harmonization, Good Clinical Practice.
- •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.
排除标准
- •Patient is recipient of a solid organ transplant other than the kidney. Patient has recurrence of primary renal disease, or de novo renal disease. Patient is pregnant or lactating. Patient had known or suspected malignancy (except for treated squamous and basal cell skin cancers) <5 years before study entry or a history of post-transplant lymphoproliferative disease (PTLD).
- •Patient has known hypersensitivity to tacrolimus, or any of the recipients of the drug.
研究组 & 干预措施
Ciclosporin
Maintain ciclosporin in combination with/without mycophenolate mofetil and with/without steroids at target trough levels of 70-150ng/mL.
干预措施: Ciclosporin (Drug)
Tacrolimus
Conversion from ciclosporin to tacrolimus at target trough levels of 5-8 ng/mL in combination with/without mycophenolate mofetil and with/without steroids.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Change in endothelial progenitor cells from baseline to month 24
时间窗: Baseline and 24 months
The primary endpoint was the effect of conversion from ciclosporin to tacrolimus based immunosuppressive therapy on endothelial progenitor cell count at month 24.
次要结局
- Renal function at baseline and after 24 months(Baseline, 24 months)
研究者
Gere Sunder-Plassmann
Principal Investigator Prof. Dr.
Medical University of Vienna