Clinical trial NCT06528015: Efficacy and Safety of Probiotics Combined With Enteric-coated Budesonide Capsules in Patients With Primary IgA Nephropathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Glomerulonephritis, IGA
Probiotics
Budesonide
Keywords: enteric-coated budesonide capsules
probiotic
primary IgA nephropathy
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: China Primary Health Care Foundation
First posted: 2024-07-30
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: UPCR
timeFrame: over the 9-month treatment phase
Secondary outcomes:
measure: UPCR
timeFrame: at 12 months
measure: 24-h urine protein excretion
timeFrame: at 9 and 12 months
measure: UACR
timeFrame: at 9 and 12 months
measure: serum Gd-IgA1
timeFrame: at 3, 6, 9 and 12 months
measure: serum BAFF and APRIL
timeFrame: at 12 months
measure: eGFR
timeFrame: at 9 and 12 months
measure: eGFR
timeFrame: 12months，24months，36months after the end of treatment
measure: UACR
timeFrame: 12months，24months，36months after the end of treatment
measure: 24-h urine protein excretion
timeFrame: 12months，24months，36months after the end of treatment
measure: renal function (including creatinine, urea, and uric acid)
timeFrame: 12months，24months，36months after the end of treatment
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
Study officials:
affiliation: Tongji Hospital
name: GANG XU
role: PRINCIPAL_INVESTIGATOR
References: