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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Proteinuria; Hereditary Nephropathy
• Intervention / Treatment: Drug: Routine Therapy; Drug: TCM+ Routine Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201102
    • Children's Hospital of Fudan University
  • Xuzhou, China
    • Xuzhou Children's Hospital
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Children's Hospital
  • Guangzhou
    • Guangzhou, Guangzhou, China
      • First Affiliated Hospital, Sun Yat-Sen University
  • Henan
    • Zhengzhou, Henan, China
      • Children's Hospital Affiliated to Zhengzhou University/Henan Children's Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Children's Hospital,Tongji Medical College, Huazhong University of Science and Technology.
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Children's Hospital of Nanjing Medical University
  • Shandong
    • Shandong, Shandong, China
      • Shandong Provincal Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Children's Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Routine Therapy; Patients receive a stable dose of ACEI/ARB drug as a routine therapy.; Other Names: ACEI/ARB; Drug: TCM+ Routine Therapy; 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.; Other Names: Gushen Juanyu Formula+ACEI/ARB
Experimental: 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.	Drug: Routine Therapy; Patients receive a stable dose of ACEI/ARB drug as a routine therapy.; Other Names: ACEI/ARB; Drug: TCM+ Routine Therapy; 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.; Other Names: Gushen Juanyu Formula+ACEI/ARB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in urinary protein-creatinine ratio (UPCR) from baseline to 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.	baseline, week 12, week 14, week 26
Changes in estimated glomerular filtration rate (eGFR) from baseline to 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.	baseline, week 12, week 14, week 26
Percentage change in urinary albumin-creatinine ratio (UACR) from baseline to 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.	baseline, week 12, week 14, week 26
Percentage change in 24-hour protein from baseline to week 26	24-hour urine samples are measured at baseline, week 12, week 14, and week 26. 24-hour proteinuria is a repeated measurement.	baseline, week 12, week 14, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum albumin from baseline to week 26	Serum albumin are measured at baseline, week 12, week 14, and week 26. Serum albumin is a repeated measurement.	baseline, week 12, week 14, week 26
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 26. The minimum values is 0 and maximum values is 36. The higher scores mean a severe status.	Baseline, week 26
Changes in liver function parameters from baseline to week 26: Alanine Aminotransferase (ALT)	Blood samples are measured at baseline, week 12, week 14, week 26 to evaluate ALT	baseline, week 12, week 14, week 26
Changes in liver function parameters from baseline to week 26: Aspartate Aminotransferase (AST)	Blood samples are measured at baseline, week 12, week 14, week 26 to evaluate AST	baseline, week 12, week 14, week 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects reporting adverse events （AEs）during the treatment period	Number of subjects with AEs as a measure of safety	baseline to week 26

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Shandong Provincial Hospital; Henan Provincial People's Hospital; Wuhan Union Hospital, China; The Children's Hospital of Zhejiang University School of Medicine; Children's Hospital of Nanjing Medical University; Xuzhou Children Hospital; Anhui Provincial Children's Hospital
• Investigators: Study Chair: Hong Xu, PhD, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2023
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: February 26, 2023
• First Submitted That Met QC Criteria: February 26, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Traditional Chinese Medicine; anti-proteinuric
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Kidney Diseases; Proteinuria; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Angiotensin-Converting Enzyme Inhibitors
• Other Study ID Numbers: TCMinpKD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No