Budesonide, Glomerulonephritis, IGA, Probiotics
Conditions
Keywords
enteric-coated budesonide capsules, probiotic, primary IgA nephropathy
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.
Interventions
DRUGprobiotics 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.
DRUGprobiotics 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.
Sponsors
China Primary Health Care Foundation
Gang Xu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| UPCR | over the 9-month treatment phase | Mean change from baseline in UPCR over the 9-month treatment phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-h urine protein excretion | at 9 and 12 months | Mean changes from baseline in 24-h urine protein excretion at 9 and 12 months |
| UACR | at 9 and 12 months | Mean changes from baseline in UACR at 9 and 12 months |
| serum Gd-IgA1 | at 3, 6, 9 and 12 months | Mean changes from baseline in serum Gd-IgA1 at 3, 6, 9 and 12 months |
| UPCR | at 12 months | Mean change from baseline in UPCR at 12 months |
| eGFR | at 9 and 12 months | Mean changes from baseline in eGFR at 9 and 12 months |
| renal function (including creatinine, urea, and uric acid) | 12months，24months，36months after the end of treatment | Changes from baseline in renal function (including creatinine, urea, and uric acid) at each visit during long-term follow-up |
| serum BAFF and APRIL | at 12 months | Mean changes from baseline in serum BAFF and APRIL at 12 months |
Countries
China
Contacts
Primary ContactRUI ZENG
Backup ContactGANG XU
Outcome results
None listed