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

NCT ID: NCT06528015

Last Updated: 2024-07-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2028-12-31

Brief Summary

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

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.

Conditions

Glomerulonephritis, IGA; Probiotics; Budesonide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Experimental

Experimental participants will receive probiotics combined with enteric-coated budesonide capsules

Group Type: EXPERIMENTAL

probiotics combined with enteric-coated budesonide capsule

Intervention Type: DRUG

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.

Comparator

Comparator participants will receive probiotics placebo combined with enteric-coated budesonide capsules

Group Type: PLACEBO_COMPARATOR

probiotics placebo combined with enteric-coated budesonide capsules

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Primary Health Care Foundation

UNKNOWN

Sponsor Role: collaborator

Gang Xu

OTHER

Sponsor Role: lead

Responsible Party

Gang Xu

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

GANG XU

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, China

Countries

China

Central Contacts

RUI ZENG

Role: CONTACT

zengrui@tjh.tjmu.edu.cn

+86 15002726366

GANG XU

Role: CONTACT

xugang@tjh.tjmu.edu.cn

+86 13507181312

Other Identifiers

TongjiHospitalxugangtjh123

Identifier Type: -

Identifier Source: org_study_id