Treatment Effects of Traditional Chinese Medicine (Gu Shen Juan Yu Formula) in Children With Inherited Proteinuric Kidney Disease：A Multicenter, Open-Label, Two-Arm, Crossover Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 9
- 主要终点
- Percentage change in urinary protein-creatinine ratio (UPCR) from baseline to week 26
研究概览
简要总结
The purpose of this study is to determine whether traditional Chinese medicine, Gu Shen Juan Yu Formula, as complementary treatment is safe and effective in the treatment of Inherited Proteinuric Kidney Disease.
详细描述
Current therapy for inherited proteinuric kidney disease remains limited. Renin-angiotensin-aldosterone-system (RAAS) inhibitors such as Angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) help to control proteinuria and slow the progression of kidney function loss. However, a substantial proportion of patients progress to end-stage renal disease, which is partly associated with high residual proteinuria. Novel therapies to decrease proteinuria and limit CKD progression are needed. Traditional Chinese medicine (TCM) has been extensively used in China for thousands of years and favored in treatment of chronic disease for multi-factorial, multi-target action.
The investigators' hypothesis is that this traditional Chinese medicine, targeted to podocyte injury and repair named Gu Shen Juan Yu Formula, can significantly reduce proteinuria and delay renal function loss in patients with proteinuric kidney disease. To test this hypothesis, the investigators plan to initiate a multicenter, open-label, two-arm, crossover, randomized clinical trial in 72 children with proteinuria kidney disease. The study population will consist of children with proteinuria who are on receiving routine therapy such as ACE inhibitor or angiotensin II receptor blocker treatment. In this study, participants were randomly assigned (1:1) to receive first either TCM+Routine Therapy or Routine Therapy for 12 weeks. A 2 weeks washout period was used before crossover.
The primary objective was to measure the change of urine protein excretion and estimated glomerular filtration rate (eGFR) during the treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 3-18 years；
- •Proteinuria associated with hereditary nephropathy, which was confirmed by mutations in podocyte genes or syndromal genes (including collagens);
- •Urine protein more than 500 mg/24 hours and/or UPCR (in first-morning void) more than 0.5 mg/mg at time of baseline despite ACEI or ARB treatment for at least 3 months;
- •Estimated GFR ≥ 45 ml/min/1.73m2 (estimated with Schwartz formula);
- •Without any immunosuppressive medications such as corticosteroids, calcineurin inhibitors, etc；
- •On a stable dose of ACEI or ARB for at least 4 weeks；
- •Willingness to give written consent and comply with the study protocol.
排除标准
- •Diagnosed with Nephronophthisis, Polycystic kidney disease etc;
- •With abnormal liver function, ALT or AST >3.0 x upper limit of normal (ULN) at enrollment;
- •Receiving immunosuppressive therapy (including corticosteroids, and other immune suppressive medicine) within three months prior to enrollment;
- •Receiving other traditional Chinese medicine and/or its analogue which can reduce proteinuria within the past 2 weeks. Patients who are taking other TCM treatment could be enrolled after 2 weeks of wash out period;
- •Has undergone major organ transplantation (e.g. heart, kidney, liver);
- •Any medication, surgical or medical condition which might significantly alter the absorption, distribution, or metabolism including, but not limited to any of the following: active inflammatory bowel disease, received major gastrointestinal tract surgery;
- •History of noncompliance to medical regimens or inability to comply with the study and follow-up procedures.
研究组 & 干预措施
Group A
TCM+Routine therapy are used first for 12 weeks, followed by 2 weeks wash-out period, then Routine therapy for 12 weeks.
TCM as Gu Shen Juan Yu Formula: 3g or 6g or 12g each time based on weight (3g for W≤20kg, 6g for 20-30kg, or 12g for W>30kg), 2 times a day for 12 weeks, orally.
The GSJYF samples were made and packed by Shanghai Fangxin Pharmaceutical Technology Co., LTD. with lot number of 20230830.
Routine therapy: with stable dose of ACE inhibitors/ angiotensin II receptor blocker.
干预措施: TCM+ Routine Therapy (Drug)
Group A
TCM+Routine therapy are used first for 12 weeks, followed by 2 weeks wash-out period, then Routine therapy for 12 weeks.
TCM as Gu Shen Juan Yu Formula: 3g or 6g or 12g each time based on weight (3g for W≤20kg, 6g for 20-30kg, or 12g for W>30kg), 2 times a day for 12 weeks, orally.
The GSJYF samples were made and packed by Shanghai Fangxin Pharmaceutical Technology Co., LTD. with lot number of 20230830.
Routine therapy: with stable dose of ACE inhibitors/ angiotensin II receptor blocker.
干预措施: Routine Therapy (Drug)
Group B
Routine therapy are used first for 12 weeks, followed by 2 weeks wash-out period, then TCM+Routine therapy for 12 weeks.
TCM as Gu Shen Juan Yu Formula: 3g or 6g or 12g each time based on weight (3g for W≤20kg, 6g for 20-30kg, or 12g for W>30kg), 2 times a day for 12 weeks, orally.
The GSJYF samples were made and packed by Shanghai Fangxin Pharmaceutical Technology Co., LTD. with lot number of 20230830.
Routine therapy: with stable dose of ACE inhibitors/ angiotensin II receptor blocker.
干预措施: TCM+ Routine Therapy (Drug)
Group B
Routine therapy are used first for 12 weeks, followed by 2 weeks wash-out period, then TCM+Routine therapy for 12 weeks.
TCM as Gu Shen Juan Yu Formula: 3g or 6g or 12g each time based on weight (3g for W≤20kg, 6g for 20-30kg, or 12g for W>30kg), 2 times a day for 12 weeks, orally.
The GSJYF samples were made and packed by Shanghai Fangxin Pharmaceutical Technology Co., LTD. with lot number of 20230830.
Routine therapy: with stable dose of ACE inhibitors/ angiotensin II receptor blocker.
干预措施: Routine Therapy (Drug)
结局指标
主要结局
Percentage change in urinary protein-creatinine ratio (UPCR) from baseline to week 26
时间窗: baseline, week 12, week 14, week 26
UPCR in first-morning spot urine samples are measured at baseline, week 12, week 14, and week 26. It is a repeated measurement.
Changes in estimated glomerular filtration rate (eGFR) from baseline to week 26
时间窗: baseline, week 12, week 14, week 26
eGFR will be evaluated using Schwartz formula (eGFR=k\*height(cm)/serum creatinine(umol/L)), k=36.5). Serum creatinine are measured at baseline, week 12, week 14, week 26. Serum creatinine is a repeated measurement.
Percentage change in urinary albumin-creatinine ratio (UACR) from baseline to week 26
时间窗: baseline, week 12, week 14, week 26
UACR in first-morning spot urine samples are measured at baseline, week 12, week 14, and week 26. UPCR is a repeated measurement.
Percentage change in 24-hour protein from baseline to week 26
时间窗: baseline, week 12, week 14, week 26
24-hour urine samples are measured at baseline, week 12, week 14, and week 26. 24-hour proteinuria is a repeated measurement.
次要结局
- Changes in serum albumin from baseline to week 26(baseline, week 12, week 14, week 26)
- Changes of Traditional Chinese Medicine syndrome scores after treatment(Baseline, week 26)
- Changes in liver function parameters from baseline to week 26: Alanine Aminotransferase (ALT)(baseline, week 12, week 14, week 26)
- Changes in liver function parameters from baseline to week 26: Aspartate Aminotransferase (AST)(baseline, week 12, week 14, week 26)