Clinical Trial Technology Development for the Validation of Surrogate Prognostic Markers in Patients With Diabetic Nephropathy
Worldwide, the most common cause of chronic kidney disease (CKD) and end stage renal disease (ESRD) is diabetes. Unlike the past, in south korea, diabetes account for more than 40% of ESRD. According to WHO reports in 1998, 100 million people had type 2 diabetes in 1997, and there is expected to increase by 300 million people in 2025. In addition, the expected survival time of patients with diabetes increase compared to previous. In the future, ESRD due to type 2 diabetes is expected to have a significant impact on the health industry. Therefore, prevention of progression to CKD and ESRD in diabetic patients is important to aspect of national health and economic problems. How to stop the progression of diabetic nephropathy is part of modern medicine to be solved.
Strict glycemic control, blood pressure regulation, and use of renin-angiotensin system (RAS) blockers inhibit the development and progression of diabetic nephropathy. Microalbuminuria in diabetic patients has been recognized as a predictor of progression of diabetic nephropathy. Thus, the prevention of elevated urinary albumin excretion is an important therapeutic target for the prevention of renal and cardiovascular events.
In patients with diabetes and hypertension, the drugs that block the RAS are used to treat proteinuria, but still a large number of patients with proteinuria are uncontrolled. In addition, ACE inhibitors or ARB agents actually have a limited effect on reducing the risk of cardiovascular or renal outcome. Also, sulodexide or pentoxyphylline which is reducing proteinuria have some weak evidence in terms of efficacy and safety. Therefore, the introduction of new alternative drugs are required.
Already several study reported that calcitriol or paricalcitol in the renal injury model have renopreventive effect. In addition, in diabetic renal injury mice model reported that vitamin D receptor deficiency leads to glomerulosclerosis. Inhibition of the RAS with combination of paricalcitol and RAS inhibitors effectively prevent renal injury in diabetic nephropathy. Recently, Dick de Zeeuw et al reported that addition of paricalcitol to RAS inhibition safely lower residual albuminuria in patients with diabetic nephropathy. Recent studies reported that elevated concentrations of serum markers of the TNFα and Fas-pathways are strongly associated with decreased renal function in diabetic patients. However, the role of these markers in early progressive renal function decline are not clear. Therefore, the objective of this study is to identify the renoprotective effect as an new treatment of activated vitamin D (Calcitriol) indicating the TNF-α-related anti-inflammatory action and to seek the role as an important biomarker that the changes of TNFR in diabetic nephropathy can predict response to treatment.
研究概览
研究类型
注册 (预期的)
阶段
- 第四阶段
联系人和位置
学习地点
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Seoul、大韩民国、110-744
- 招聘中
- Seoul National University Hospital
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接触：
- Yonsu Kim, M.D., Ph.D
- 电话号码：82-2-2072-2264
- 邮箱：yonsukim@snu.ac.kr
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接触：
- Dongki Kim, M.D., Ph.D
- 电话号码：82-2-2072-2303
- 邮箱：dkkim73@gmail.com
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首席研究员：
- Yonsu Kim, Ph.D.
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副研究员：
- Dongki Kim, M.D., Ph.D
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副研究员：
- Sumi Lee, M.D.
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Seoul、大韩民国
- 尚未招聘
- Seoul National University Boramae Medical Center
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接触：
- Jungpyo Lee, M.D., Ph.D
- 电话号码：82-2-870-2261
- 邮箱：kjwa1@medimail.co.kr
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副研究员：
- Jungpyo Lee, M.D., Ph.D
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- patients age 19-80 years
- Clinically proven diabetic nephropathy
- MDRD eGFR >= 30mL/min/1.73m2
- Patients with residual urine protein/creatinine ratio >= 200mg/g
- Adequate blood pressure control as treated systolic blood pressure <=140 or diastolic <=90 mmHg with RAS inhibitor for more than 3months
- Serum intact PTH <500 mg/dL
- Serum calcium <10.2 mg/dL
- Patients who have not been treated vitamin D within the 3months prior to signing the informed consent form
Exclusion Criteria:
- Patients age <19 years or > 80years
- Patients with rapidly progressive glomerulonephritis
- Patients requiring renal replacement therapy immediately
- Hypercalcemia(Uncorrected serum calcium level >10.2 mg/dL) within recent 3month
- Malignant hypertension
- Heart failure (New York Heart Association functional class II to IV or LVEF <40%)
- Severe chronic obstructive lung disease
- Decompensated liver disease (ALT >3X upper normal limit)
- Known allergy or hypersensitivity to vitamin D
- Current treatment with steroids and/or immunosuppressive agents
- Active primary malignancy requiring treatment or survival limits less than 2years
- History of noncompliance to medical regimen
- Inability to give an informed consent or to cooperate with researchers
学习计划
研究是如何设计的？
设计细节
- 主要用途：放映
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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安慰剂比较：安慰剂
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实验性的：Calcitriol
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dosage of 0.5mcg administered orally once daily for 12 month
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Changes in renal function with proteinuria
大体时间：12 month after administration
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Comparison of in GFR level from baseline Comparison of proteinuria amount checked by random urine protein/creatinine ratio
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12 month after administration
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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changes in sTNFR and TNF-related proteins
大体时间：12 months after administration
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Comparison of serum TNFR1, TNFR2 levels from baseline
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12 months after administration
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合作者和调查者
调查人员
- 学习椅：Yonsu Kim, M.D., Ph.D、Seoul National University Hospital
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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