Efficacy and Safety of Probiotics Combined With Enteric-coated Budesonide Capsules in Patients With Primary IgA Nephropathy

Efficacy and Safety of Probiotics Combined With Enteric-coated Budesonide Capsules in Patients With Primary IgA Nephropathy: a Prospective, Multicenter, Randomized, Single-blind, Placebo-controlled Clinical Trial

The goal of this clinical trial is to evaluate the efficacy and safety of probiotics combined with enteric-coated budesonide capsule in patients with IgA nephropathy on the basis of optimized RAS blockade therapy, and to explore the correlation between the efficacy of probiotics combined with enteric-coated budesonide capsule in the treatment of primary IgA nephropathy and intestinal homeostasis.

The main questions it aims to answer are:

Dose probiotics combined with enteric-coated budesonide capsule provide a durable reduction in urine protein creatinine ratio (UPCR) in participants, compared with probiotics placebo combined with enteric-coated budesonide capsule? What medical problems do participants have when taking probiotics combined with enteric-coated budesonide capsule?

Participants will:

Take probiotics combined with enteric-coated budesonide capsules or probiotics placebo combined with enteric-coated budesonide capsules every day for 9.5 month Participate in center site follow-up visits for 13 times Keep a diary of their symptoms and outcomes

Study Overview

• Status: Not yet recruiting
• Conditions: Probiotics; Glomerulonephritis, IGA; Budesonide
• Intervention / Treatment: Drug: probiotics combined with enteric-coated budesonide capsule; Drug: probiotics placebo combined with enteric-coated budesonide capsules

Detailed Description

This is a prospective, multicenter, randomized, single-blind, placebo-controlled clinical trial. The study included a screening period (7-15 days), an induction period (at least 3 months), randomization, a treatment period (9 months), a reduction period (2 weeks), a safety follow-up period (2.5 months), and a long-term follow-up period (36 months). Participants who meet the randomization criteria will be randomly assigned (1:1) to receive probiotics combined with enteric-coated budesonide capsules or probiotics placebo combined with enteric-coated budesonide capsules.

Screening period (7-15 days): Participants who sign the informed consent for this study and undergo relevant examinations can enter the induction period if they meet the screening criteria.

Induction period (at least 3 months): Optimized treatment with RAS blockers is performed immediately upon entry the induction period.

Randomization: RAS blockers were used for at least 3 months during the induction period. All inclusion conditions had to be met to qualify for randomization.

Treatment period (9 months): Participants who meet the randomization criteria will be randomly assigned (1:1) to receive probiotics combined with enteric-coated budesonide capsules group or probiotics placebo combined with enteric-coated budesonide capsules. In the 9-month treatment period, the following treatments will be received: ① probiotics combined with enteric-coated budesonide capsules group: 1 bag/day of probiotics (each bag added active probiotic Lactobacillus casei Zhang ≥100 billion CFU) +16 mg/day oral enteric-coated budesonide capsules. ② probiotics placebo combined with enteric-coated budesonide capsules group: 1 bag/day of probiotics placebo +16 mg/day oral enteric-coated budesonide capsules.

The RAS blocker (ACEI or ARB) dosing regimen needs to be stable during treatment period.

Reduction period (2 weeks): After completing the treatment period, participants will enter a 2-week reduction period to reduce the risk of adrenal insufficiency. ① enteric-coated budesonide capsules reduction: 8 mg/day oral enteric-coated budesonide capsules.

The RAS blocker (ACEI or ARB) dosing regimen needs to be stable during reduction period.

Safety follow-up period (2.5 months): After completion of the reduction period, all participants stopped taking the investigational drug, completed the remainder of the safety follow-up period. During this time, the RAS blocker (ACEI or ARB) dosing regimen needs to be stable.

Long-term follow-up period (36 months): Participants who have completed the treatment period, reduction period, and safety follow-up period, as well as those who terminated the study treatment early but did not withdraw from the study, will enter long-term follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 206
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: RUI ZENG; Phone Number: +86 15002726366; Email: zengrui@tjh.tjmu.edu.cn
• Study Contact Backup: Name: GANG XU; Phone Number: +86 13507181312; Email: xugang@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult age: 18~70 years old;
2. Renal biopsy-confirmed primary IgA nephropathy;
3. 24-h urine protein excretion ≥ 0.75g, or urinary protein creatinine ratio (UPCR) ≥ 0.5g/g;
4. eGFR ≥ 30mL/min/1.73m^2 estimated with the Chronic Kidney Disease Epidemiology Collaboration 2009 formula (CKD-EPI2009);
5. Fertile men and female of childbearing age need to use highly effective contraceptive measures from the time they sign informed consent to the end of the safety follow-up period;
6. Sign the informed consent, understand and agree to comply with the requirements of the study and the trial procedures.

Exclusion Criteria:

1. Secondary form of IgA nephropathy or any non-IgA nephropathy Glomerulonephritis;
2. Specific types of IgA nephropathy (including minor lesions with mesangial IgA deposition, rapidly progressive and crescentic IgA nephropathy, etc.) and other glomerular diseases (such as diabetic nephropathy, etc.);
3. 24-h urine protein excretion >5g;
4. Renal biopsy showed crescent ≥25%;
5. A history of severe gastrointestinal disease (such as active peptic ulcer disease, active gastrointestinal bleeding, gastrointestinal perforation, inflammatory bowel disease, and chronic diarrhea) or a history of gastrointestinal surgery;
6. Complicated with malignant tumors (diagnosed within the past 5 years), cerebral infarction, cerebral hemorrhage, myocardial infarction, arrhythmia, heart failure and other serious primary diseases;
7. The presence of severe chronic or active infections (including but not limited to tuberculosis) that require systemic antimicrobial, antifungal, antiviral, or antiparasitic treatment;
8. A history of cirrhosis;
9. Severe osteoporosis requiring treatment;
10. Received organ transplants;
11. Glaucoma or cataracts who currently require clinical treatment;
12. Diagnosed with uncontrolled mental illness;
13. Participants with poorly controlled type 1 or type 2 diabetes (glycated haemoglobin [HbA1c] >8%;
14. Laboratory tests for abnormal liver function (ALT and/or AST> 2 times the upper normal limit, ALP> 2.5 times the upper normal limit);
15. The blood total cholesterol was seriously abnormal (>12.92mmol/L);
16. Human immunodeficiency virus antibody positive, treponema pallidum antibody positive, hepatitis B surface antigen positive, hepatitis C antibody positive;
17. Currently using a potent inhibitor of cytochrome P4503A4 (CYP3A4) and cannot be discontinued during the study;
18. Known allergy or intolerance to ACEI, ARB, budesonide or any component of the investigational drug formulation;
19. Use of antibiotics, glucocorticoids or other immunosuppressants, foods and medicines containing probiotics/prebiotics within the past 3 months;
20. Pregnant or lactating participants;
21. Also accepting participants from other clinical trials;
22. Participants who have been determined by the researchers to be unable to complete on time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Experimental participants will receive probiotics combined with enteric-coated budesonide capsules	Drug: probiotics combined with enteric-coated budesonide capsule; In the 9-month treatment period, the following treatments will be received: probiotics combined with enteric-coated budesonide capsules group: 1 bag/day of probiotics (each bag added active probiotic Lactobacillus casei Zhang ≥100 billion CFU) +16 mg/day oral enteric-coated budesonide capsules. After completing the treatment period, participants will enter a 2-week reduction period to reduce the risk of adrenal insufficiency. ① enteric-coated budesonide capsules reduction: 8 mg/day oral enteric-coated budesonide capsules.
Placebo Comparator: Comparator; Comparator participants will receive probiotics placebo combined with enteric-coated budesonide capsules	Drug: probiotics placebo combined with enteric-coated budesonide capsules; In the 9-month treatment period, the following treatments will be received: probiotics placebo combined with enteric-coated budesonide capsules group: 1 bag/day of probiotics placebo +16 mg/day oral enteric-coated budesonide capsules. After completing the treatment period, participants will enter a 2-week reduction period to reduce the risk of adrenal insufficiency. ① enteric-coated budesonide capsules reduction: 8 mg/day oral enteric-coated budesonide capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UPCR	Mean change from baseline in UPCR over the 9-month treatment phase	over the 9-month treatment phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UPCR	Mean change from baseline in UPCR at 12 months	at 12 months
24-h urine protein excretion	Mean changes from baseline in 24-h urine protein excretion at 9 and 12 months	at 9 and 12 months
UACR	Mean changes from baseline in UACR at 9 and 12 months	at 9 and 12 months
serum Gd-IgA1	Mean changes from baseline in serum Gd-IgA1 at 3, 6, 9 and 12 months	at 3, 6, 9 and 12 months
serum BAFF and APRIL	Mean changes from baseline in serum BAFF and APRIL at 12 months	at 12 months
eGFR	Mean changes from baseline in eGFR at 9 and 12 months	at 9 and 12 months
eGFR	Changes from baseline in eGFR at each visit during long-term follow-up	12months，24months，36months after the end of treatment
UACR	Changes from baseline in UACR at each visit during long-term follow-up	12months，24months，36months after the end of treatment
24-h urine protein excretion	Changes from baseline in 24-h urine protein excretion at each visit during long-term follow-up	12months，24months，36months after the end of treatment
renal function (including creatinine, urea, and uric acid)	Changes from baseline in renal function (including creatinine, urea, and uric acid) at each visit during long-term follow-up	12months，24months，36months after the end of treatment

Collaborators and Investigators

• Sponsor: Gang Xu
• Collaborators: China Primary Health Care Foundation
• Investigators: Principal Investigator: GANG XU, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: probiotic; primary IgA nephropathy; enteric-coated budesonide capsules
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis; Glomerulonephritis, IGA; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: TongjiHospitalxugangtjh123

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No