Randomized, Double-blind, Placebo-Controlled Study on Efficacy of a Dietary Intervention With Probiotic Bacterial Strains as an Adjunct to Treatment of Small Intestinal Bacterial Overgrowth With Rifaximin
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 129
- 试验地点
- 1
- 主要终点
- Change in bloating on Visual Analog Score
研究概览
简要总结
The goal of this clinical trial is to test the effectiveness of probiotic bacterial supplements as an additional therapeutic modality in patients with small intestine bacterial overgrowth who receive oral antibiotic treatment (rifaximin)
The main questions it aims to answer are:
1 To evaluate the effectiveness of a dietary intervention using pro-biotic bacterial strains as an adjunct to treatment of SIBO with rifaximin.
2. Evaluation of ultrasonographic imaging of mesenteric lymph nodes in patients with SIBO.
3. Evaluation of the effect of rifaximin treatment and dietary intervention on non-alcoholic fatty liver disease activity parameters in patients with coexisting NAFLD and SIBO.
According to the study schedule, a total of 3 visits will be made within 3 months. Visit 1, after 6 weeks Visit 2 and after another 6 weeks, Visit 3. Patients will also be invited to a follow-up Visit 4, three months after completing participation in the study.
All study participants will receive treatment recommendations for SIBO in accordance with standard practice - a 14-day antibiotic treatment with Rifaximin.
In addition, a randomly selected half of the study participants will receive probiotic therapy and half a placebo.
- An ultrasound examination of the mesenteric root lymph nodes will be performed at each visit,
- followed by a lier steatosis/fibrosis assessment using SWE elastography or FibroScan.
- Blood sampling is required on each visit. All study participants will receive detailed guidelines during dietary consultations at each visit for the use of a low FODMAP diet.
- Each participant will receive a paper diary on how to assess the severity of bloating and evaluate bowel movements, which must be filled out daily.
- In addition, at the visits the patient will be asked to fill out an additional questionnaire on other gastrointestinal complaints and mental health.
详细描述
The investigators plan to include 100 participants in the study. The control group will consist of healthy subjects (25 subjects) without SIBO (with a negative hydrogen-methane test) and without NAFLD (CAP<248dB/m, TE<6.5kPa). These patients will have only one visit, at which an abdominal ultrasound will be performed with assessment of mesenteric root lymph nodes, and blood will be drawn for biochemical tests, as well as blood and stool for determination of intestinal barrier integrity markers.
The experiment will be conducted at SONOMED Medical Center from April 2023. until April 2025.
According to the survey scheme, a total of 4 visits will be made during the project. The planned procedures at each visit are outlined below.
Table 1 Scheme of the study Visit 1 (Week 0)
- Ultrasound of the mesenteric root
- SWE elastography, UGAP and Fibroscan (in everyone to identify the subgroup with NAFLD)
- Prescription issue: Xifaxan 1200mg/d for 14 days (3 packs, 28 tablets each)
- Randomization
- drug issue: 4Enteric/Placebo
- Consultation of a nutritionist (issuance of recommendations for stage 1 of the low FODMAP diet)
- anthropometric measurements
- blood draw
- collection of a stool sample
- completion of ailment questionnaires
- Completion of nutrition and physical activity questionnaires
- issuance of SIBO symptom diaries
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 (Investigator)
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
- •positive hydrogen OR methane breath test
- •SIBO symptoms seen as:
- •moderate or severe bloating for at least 50% of days in the past 3 months if hydrogen test (+) OR constipation (< 3 bowel movements/week) in the past 3 months if methane test (+)
排除标准
- •age >70,
- •current proton pump inhibitor therapy,
- •antibiotic therapy in the past 3 months,
- •probiotic therapy in the past 2 weeks,
- •daily intake of >30 g of ethanol for men
- •daily intake of >20 g of ethanol for women,
- •hepatitis B or C virus infection,
- •other liver disease,
- •celiac disease,
- •severe chronic disease (m.e.g. chronic kidney disease, congestive heart failure, cancer, liver failure),
- •current symptoms of acute infection,
- •pregnancy,
- •vegan diet or following non-recommended diets such as ketogenic,
- •patients with very high physical activity (> 5 x week of 100 min of strength training).
研究组 & 干预措施
Probiotic+Rifaximin 1200mg/day
Dosage 2x1 capsule/day. 12 weeks
Probiotic, which will contain a combination of four freeze-dried strains of probiotic bacteria in DRcaps enteral capsulesTM . These are capsules that protect the probiotics from the effects of hydrochloric acid in the stomach, as they only dissolve in the intestines. The tested composition of probiotics is on sale in Poland, Italy, Taiwan, among other countries. It has a positive recommendation of the Institute "Pomnik-Center for Children's Health" No. 16/DJW/2022.
(Lactococcus lactis Rosell® - 1058, Lactobacillus casei Rosell® - 215, Lactobacillus helvetius Rosell® - 52, Bifidobacterium bifidum Rosell® - 71) AND Rifaximin at a dose of 1200 mg/d for 14 days (Xifaxan 200 mg, 3 op. of 28 tablets, DS. 3 x 400mg)
干预措施: Rifaximin (Xifaxan) 1200mg/day (Drug)
Probiotic+Rifaximin 1200mg/day
Dosage 2x1 capsule/day. 12 weeks
Probiotic, which will contain a combination of four freeze-dried strains of probiotic bacteria in DRcaps enteral capsulesTM . These are capsules that protect the probiotics from the effects of hydrochloric acid in the stomach, as they only dissolve in the intestines. The tested composition of probiotics is on sale in Poland, Italy, Taiwan, among other countries. It has a positive recommendation of the Institute "Pomnik-Center for Children's Health" No. 16/DJW/2022.
(Lactococcus lactis Rosell® - 1058, Lactobacillus casei Rosell® - 215, Lactobacillus helvetius Rosell® - 52, Bifidobacterium bifidum Rosell® - 71) AND Rifaximin at a dose of 1200 mg/d for 14 days (Xifaxan 200 mg, 3 op. of 28 tablets, DS. 3 x 400mg)
干预措施: Probiotic (Dietary Supplement)
Placebo+Rifaximin 1600mg/day
Capsules that look identical to the probiotic and contain potato starch and a shell: hydroxypropylmethylcellulose, gellan gum.
Dosage 2x1 capsule per day. 12 weeks AND Rifaximin at a dose of 1600 mg/d for 14 days (Xifaxan 200 mg, 4 op. of 28 tablets, DS. 4 x 400mg)
干预措施: XIFAXAN® (Rifaximin) 1600mg/day (Drug)
Probiotic + Rifaximin 1600mg/day
Dosage 2x1 capsule/day. 12 weeks
Probiotic, which will contain a combination of four freeze-dried strains of probiotic bacteria in DRcaps enteral capsulesTM . These are capsules that protect the probiotics from the effects of hydrochloric acid in the stomach, as they only dissolve in the intestines. The tested composition of probiotics is on sale in Poland, Italy, Taiwan, among other countries. It has a positive recommendation of the Institute "Pomnik-Center for Children's Health" No. 16/DJW/2022.
(Lactococcus lactis Rosell® - 1058, Lactobacillus casei Rosell® - 215, Lactobacillus helvetius Rosell® - 52, Bifidobacterium bifidum Rosell® - 71) AND Rifaximin at a dose of 1600 mg/d for 14 days (Xifaxan 200 mg, 4 op. of 28 tablets, DS. 4 x 400mg)
干预措施: Probiotic (Dietary Supplement)
Probiotic + Rifaximin 1600mg/day
Dosage 2x1 capsule/day. 12 weeks
Probiotic, which will contain a combination of four freeze-dried strains of probiotic bacteria in DRcaps enteral capsulesTM . These are capsules that protect the probiotics from the effects of hydrochloric acid in the stomach, as they only dissolve in the intestines. The tested composition of probiotics is on sale in Poland, Italy, Taiwan, among other countries. It has a positive recommendation of the Institute "Pomnik-Center for Children's Health" No. 16/DJW/2022.
(Lactococcus lactis Rosell® - 1058, Lactobacillus casei Rosell® - 215, Lactobacillus helvetius Rosell® - 52, Bifidobacterium bifidum Rosell® - 71) AND Rifaximin at a dose of 1600 mg/d for 14 days (Xifaxan 200 mg, 4 op. of 28 tablets, DS. 4 x 400mg)
干预措施: XIFAXAN® (Rifaximin) 1600mg/day (Drug)
Placebo+Rifaximin 1200mg/day
Capsules that look identical to the probiotic and contain potato starch and a shell: hydroxypropylmethylcellulose, gellan gum.
Dosage 2x1 capsule per day. 12 weeks AND Rifaximin at a dose of 1200 mg/d for 14 days (Xifaxan 200 mg, 3 op. of 28 tablets, DS. 3 x 400mg)
干预措施: Rifaximin (Xifaxan) 1200mg/day (Drug)
结局指标
主要结局
Change in bloating on Visual Analog Score
时间窗: 12 weeks
Visual Analog Score (range 0-10, the lower the better) reduction in bloating by 50% in patients with a baseline positive hydrogen test
Change in bowel movements in a bowel-movement diary
时间窗: 12 weeks
increase in bowel frequency by 1/week in patients with a baseline positive methane test
次要结局
- Changes in the microbiome and metabolome(12 weeks)
- Change of hepatic fibrosis - Transient Elastography(12 weeks)
- Changes in liver tests - triglycerides(12 weeks)
- The number of patients with a negative hydrogen test(12 weeks)
- Changes in liver tests - alanine transaminase (ALT)(12 weeks)
- Changes in liver function - Fatty Liver Index(12 weeks)
- Change in intestinal permeability parameters - intestinal fatty acid binding protein(12 weeks)
- Change in intestinal permeability parameters - calprotectin(12 weeks)
- Change in intestinal permeability parameters - fecal zonulin content(12 weeks)
- The number of patients with a negative methane test(12 weeks)
- Change in mesenteric root lymph node ultrasound(12 weeks)
- Improved indices of liver function and metabolism(12 weeks)
- Changes in liver tests - aspartate transaminase (AST)(12 weeks)
- Changes in liver tests - Gamma-glutamyl transpeptidase (GGTP or GGT)(12 weeks)
- Changes in cholesterol(12 weeks)
- Change of hepatic steatosis - Controlled Attenuation Parameter(12 weeks)
- Change of hepatic fibrosis - Shear Wave Elastography(12 weeks)
- Change in patient-reported stool quality by Bristol Stool Chart(12 weeks)
- Depression risk in Patient Health Questionnaire-9 (PHQ-9)(12 weeks)
- Change of hepatic steatosis - Ultrasound-Guided Attenuation Parameter(12 weeks)
- Change in subjective symptoms on Visual Analog Score(12 weeks)
- Change in subjective symptoms on Gastrointestinal Symptom Rating(12 weeks)