Effects of Traditional Chinese Medicine (GSJYF) in Children With Inherited Proteinuric Kidney Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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, parallel-design, randomized clinical trial in 144 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 TCM+ Routine Therapy or Routine Therapy for 12 weeks. The primary objective was to measure the change of urine protein excretion and estimated glomerular filtration rate (eGFR) during the treatment period.

Official Title
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Treatment Effects of Traditional Chinese Medicine (Gu Shen Juan Yu Formula) in Children With Inherited Proteinuric Kidney Disease：a Multicenter, Open-label, Two-arm, Parallel-design, Randomized Clinical Trial

Conditions
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Proteinuria, Kidney Diseases, Hereditary Nephropathy

Intervention / Treatment
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* Drug: TCM+ Routine Therapy
* Drug: Routine Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Traditional Chinese Medicine treatment group<br>Patients will receive 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, as an add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor blocker. The GSJYF samples were made and packed by Shanghai Fangxin Pharmaceutical Technology Co., LTD. with lot number of 20230830. Patients receiving a stable dose of ACEI/ARB will be continued. | Drug: TCM+ Routine Therapy<br>* TCM：The Gu Shen Juan Yu Formula contains 11 herbs and it is available in liquid form for patients. Patients will receive 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. Routine therapy: Patients receiving a stable dose of ACEI/ARB will be continued.<br>* Other names: Gushen Juanyu Formula+ACEI/ARB;|
| Other: Control group<br>Patients receive a stable dose of ACEI/ARB drug as a routine therapy. | Drug: Routine Therapy<br>* Patients receive a stable dose of ACEI/ARB drug as a routine therapy.<br>* Other names: ACEI/ARB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in urinary protein-creatinine ratio (UPCR) from baseline to week 12 | UPCR in first-morning spot urine samples are measured at baseline, week 4, week 8, and week 12. It is a repeated measurement. | baseline, week 4, week 8, week 12 | 
| Changes in estimated glomerular filtration rate (eGFR) from baseline to week 12 | 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 4, week 8, week12. Serum creatinine is a repeated measurement. | baseline, week 4, week 8, week 12 | 
| Percentage change in urinary albumin-creatinine ratio (UACR) from baseline to week 12 | UACR in first-morning spot urine samples are measured at baseline, week 4, week 8, and week 12. UPCR is a repeated measurement. | baseline, week 4, week 8, week 12 | 
| Percentage change in 24-hour protein from baseline to week 12 | 24-hour urine samples are measured at baseline, week 4, week 8, and week 12. 24-hour proteinuria is a repeated measurement. | baseline, week 4, week 8, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum albumin from baseline to week 12 | Serum albumin are measured at baseline, week 4, week 8, and week 12. Serum albumin is a repeated measurement. | baseline, week 4, week 8, week 12 | 
| Changes of Traditional Chinese Medicine syndrome scores after treatment | A TCM syndrome scale points are used to evaluate the Traditional Chinese Medicine syndromes at baseline, and week 12. The minimum values is 0 and maximum values is 36. The higher scores mean a severe status. | Baseline, week 12 | 
| Changes in liver function parameters from baseline to week 12: Alanine Aminotransferase (ALT) | Blood samples are measured at baseline, week 4, week 8, week 12 to evaluate ALT | baseline, week 4, week 8, week 12 | 
| Changes in liver function parameters from baseline to week 12: Aspartate Aminotransferase (AST) | Blood samples are measured at baseline, week 4, week 8, week 12 to evaluate AST | baseline, week 4, week 8, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traditional Chinese Medicine, anti-proteinuric