efficacy and safety of probiotics combined with enteric-coated budesonide capsules in patients with primary iga nephropathy

Conditions: Glomerulonephritis, IGA; Probiotics; Budesonide

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

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.

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.

Keywords: enteric-coated budesonide capsules probiotic primary iga nephropathy