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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат 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.

Первичные конечные точки

• UPCR [Срок оценки: over the 9-month treatment phase]

Вторичные конечные точки (10)

• UPCR [Срок оценки: at 12 months]
• 24-h urine protein excretion [Срок оценки: at 9 and 12 months]
• UACR [Срок оценки: at 9 and 12 months]
• serum Gd-IgA1 [Срок оценки: at 3, 6, 9 and 12 months]
• serum BAFF and APRIL [Срок оценки: at 12 months]
• eGFR [Срок оценки: at 9 and 12 months]
• eGFR [Срок оценки: 12months，24months，36months after the end of treatment]
• UACR [Срок оценки: 12months，24months，36months after the end of treatment]
• 24-h urine protein excretion [Срок оценки: 12months，24months，36months after the end of treatment]
• renal function (including creatinine, urea, and uric acid) [Срок оценки: 12months，24months，36months after the end of treatment]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology — Ухань

Идентификаторы

NCT: NCT06528015 · TongjiHospitalxugangtjh123

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗