Mechanisms and Treatment of Chronic Allograft Injury (CAI) Due to Calcineurin Inhibitor (CNI) Toxicity
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test
研究概览
简要总结
The purpose of this study is to find out how well the current drug regimen (including low Prograf dose and Myfortic, which is usually recommended to prevent any further deterioration in the kidney function) works and how safe it is when compared to a combination of Zortress and Myfortic in patients with chronic kidney injury associated with Prograf or Neoral use.
详细描述
Specific Aim 1: To investigate allograft and peripheral blood cell gene expression patterns of patients with CAI by using Affymetrix microarrays.
Hypothesis 1: Gene expression patterns of patients with biopsy findings suggesting calcineurin inhibitor (CNI) toxicity without significant tubulointerstitial infiltrates or transplant glomerulopathy might demonstrate upregulation of genes related to tissue injury, fibrosis, and extracellular matrix deposition without upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines comparing to patients with significant tubulointerstitial infiltrates and/or transplant glomerulopathy that might show upregulation of genes related to alloimmune response, such as, T and/or B lymphocyte activation markers, surface receptors, co-stimulation molecules, adhesion molecules, cytokines, and chemokines.
Specific Aim 2: The effect of everolimus (Zortress)/ mycophenolate sodium (EC-MPS, myfortic®) treatment on allograft and peripheral gene expression patterns.
Hypothesis 2: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) treatment attenuates the progression of CAI due to CNI toxicity by downregulating the expression of genes related to fibrosis, such as, transforming growth factor-β, thrombospondin 1, and platelet derived growth factor-C.
Specific Aim 3: To document the clinical outcomes of everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) in patients with CAI due to CNI toxicity Hypothesis 3: Everolimus (Zortress) and mycophenolate sodium (EC-MPS, myfortic®) can attenuate the progression of CAI due to CNI toxicity and may improve the creatinine clearance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients with biopsy proven pure chronic allograft injury due to CNI toxicity.
排除标准
- •24 hour urine protein or spot urine protein/creatinine ratio > 500 mg/day
- •Estimated glomerular filtration rate (eGFR) < 30 ml/min by modification of Diet in Renal Disease( MDRD) or 24 hour urine collection
- •Patients with Donor-specific antibody (DSA) by Luminex (mean fluorescence intensity values > 1,000)
- •Recipients of multiple organ transplants or ABO-incompatible allograft
- •Current panel reactive antibody (PRA) greater than 30 percent
- •Graft loss at randomization
- •Pregnant women
- •Previous history of acute rejection
- •Previous history of allergy or intolerance to Zortress or Myfortic
- •Platelet count less than 100,000
- •White Blood Cell (WBC) less than 3,000
- •Hb less than 9 g/dL or Htc less than 30%
- •Biopsy findings of
- •Chronic antibody mediated rejection
- •Acute rejection
- •Positive C4d staining
- •Interstitial infiltrates more than 25% of the area
- •Transplant glomerulopathy
- •Recurrent or de novo glomerular disease
- •Polyoma nephropathy or positive simian virus 40 (SV40) staining
研究组 & 干预措施
Everolimus (Zortress)
干预措施: Mycophenolic acid (Drug)
Everolimus (Zortress)
干预措施: Everolimus (Drug)
Reduced dose Tacrolimus (Prograf)
干预措施: Tacrolimus (Drug)
Reduced dose Tacrolimus (Prograf)
干预措施: Mycophenolic acid (Drug)
结局指标
主要结局
Change in eGFR (Creatinine Clearance) as Measured by Serum Creatinine Blood Test
时间窗: Baseline, One year
Estimated glomerular filtration rate (eGFR) indicates kidney function. Normal eGFR value for healthy is 80-120ml/min. For transplants, it is expected to be 60-80 ml/min.
次要结局
未报告次要终点
研究者
Enver Akalin
Prof. Dept of Medicine (Nephrology)
Montefiore Medical Center