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
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 206
- 试验地点
- 1
- 主要终点
- UPCR
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult age: 18~70 years old;
- •Renal biopsy-confirmed primary IgA nephropathy;
- •24-h urine protein excretion ≥ 0.75g, or urinary protein creatinine ratio (UPCR) ≥ 0.5g/g;
- •eGFR ≥ 30mL/min/1.73m^2 estimated with the Chronic Kidney Disease Epidemiology Collaboration 2009 formula (CKD-EPI2009);
- •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;
- •Sign the informed consent, understand and agree to comply with the requirements of the study and the trial procedures.
排除标准
- •Secondary form of IgA nephropathy or any non-IgA nephropathy Glomerulonephritis;
- •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.);
- •24-h urine protein excretion >5g;
- •Renal biopsy showed crescent ≥25%;
- •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;
- •Complicated with malignant tumors (diagnosed within the past 5 years), cerebral infarction, cerebral hemorrhage, myocardial infarction, arrhythmia, heart failure and other serious primary diseases;
- •The presence of severe chronic or active infections (including but not limited to tuberculosis) that require systemic antimicrobial, antifungal, antiviral, or antiparasitic treatment;
- •A history of cirrhosis;
- •Severe osteoporosis requiring treatment;
- •Received organ transplants;
- •Glaucoma or cataracts who currently require clinical treatment;
- •Diagnosed with uncontrolled mental illness;
- •Participants with poorly controlled type 1 or type 2 diabetes (glycated haemoglobin [HbA1c] >8%;
- •Laboratory tests for abnormal liver function (ALT and/or AST> 2 times the upper normal limit, ALP> 2.5 times the upper normal limit);
- •The blood total cholesterol was seriously abnormal (>12.92mmol/L);
- •Human immunodeficiency virus antibody positive, treponema pallidum antibody positive, hepatitis B surface antigen positive, hepatitis C antibody positive;
- •Currently using a potent inhibitor of cytochrome P4503A4 (CYP3A4) and cannot be discontinued during the study;
- •Known allergy or intolerance to ACEI, ARB, budesonide or any component of the investigational drug formulation;
- •Use of antibiotics, glucocorticoids or other immunosuppressants, foods and medicines containing probiotics/prebiotics within the past 3 months;
- •Pregnant or lactating participants;
- •Also accepting participants from other clinical trials;
- •Participants who have been determined by the researchers to be unable to complete on time.
研究组 & 干预措施
Experimental
Experimental participants will receive probiotics combined with enteric-coated budesonide capsules
干预措施: probiotics combined with enteric-coated budesonide capsule (Drug)
Comparator
Comparator participants will receive probiotics placebo combined with enteric-coated budesonide capsules
干预措施: probiotics placebo combined with enteric-coated budesonide capsules (Drug)
结局指标
主要结局
UPCR
时间窗: over the 9-month treatment phase
Mean change from baseline in UPCR over the 9-month treatment phase
次要结局
- serum BAFF and APRIL(at 12 months)
- eGFR(12months，24months，36months after the end of treatment)
- renal function (including creatinine, urea, and uric acid)(12months，24months，36months after the end of treatment)
- UPCR(at 12 months)
- 24-h urine protein excretion(12months，24months，36months after the end of treatment)
- UACR(12months，24months，36months after the end of treatment)
- serum Gd-IgA1(at 3, 6, 9 and 12 months)
研究者
Gang Xu
Professor
Tongji Hospital