Effect of Probiotics on Gut Microbiota During the Helicobacter Pylori Eradication: a Randomized Double-blind Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Gut microbiota
研究概览
简要总结
Helicobacter pylori (H. pylori) is still infecting more than half of the population in many countries, although the prevalence is decreasing. As a main cause of chronic gastritis, peptic ulcer, and malignant gastric tumors, H. pylori places a heavy burden on developing countries and regions with high infection rate. In the last decade, the eradication rates of conventional regimens based on proton pump inhibitors (PPIs) plus antibiotics have been decreasing. Antibiotic resistance and decrease of drug compliance caused by adverse effects were the two main reasons for eradication failure. Moreover, H. pylori treatment causes dysbiosis of gut microbiota and increases the expression of antibiotic resistance gene. Therefore, eradication of H. pylori is facing a great challenge, and effective and safe methods are needed.
To reduce adverse effects, improve drug compliance and increase eradication rates, certain probiotics were added to conventional regimens in several clinical studies. Probiotics were more or less shown to reduce adverse effects in the vast majority of clinical studies, but whether probiotics can improve the eradication rate of H. pylori remains controversial. Meanwhile, several studies focusing on the impact of probiotics on gut microbiota during H. pylori eradication have been published recently. Thus, we conducted a randomized, double-blind, placebo-controlled trial aiming to evaluate the effects of probiotics combining with 14-day bismuth quadruple therapy on H. pylori eradication.
详细描述
This was a randomized, parallel-group, double-blind and placebo-controlled study. If the subject meets the selection criteria but not the exclusion criteria, and signs an informed consent form, patients were randomly allocated in a 1:1 ratio to receive either the investigational product or placebo along with H. pylori eradication therapy. The randomization sequence was generated using SAS 9.1.3. Eight weeks after the eradication treatment, the subjects will review the 13C-urea breath test, and the researcher records the results. Feces samples, which were taken at the subject's home at the beginning, the end of treatment and 8 weeks after treatment completion, were collected from the patients immediately and stored at -80 °C until analysis. In this study, the influences of antibiotics and combination of probiotics on gut microbiota during H. pylori treatments were investigated using high-throughput sequencing of the 16S rRNA gene.
Patients were required to recall the history of gastrointestinal symptoms at baseline, keep the symptom diaries during the treatment and return the diaries at week 2. Gastrointestinal symptoms were assessed and scored according to the 15-iteem GSRS27 before (week 0) and after quadruple therapy (week 2). Special attention was given to the following symptoms: epigastric pain, heartburn, acid regurgatition, nausea or/and vomiting, abdominal distension, eructation, diarrhea, constipation. Adverse effects outside gastrointestine were also recorded and evaluated.
Compliance with antibiotic therapy and the investigational product was evaluated by means of a patient's diary and product accountability, while compliance with eradication therapy was evaluated through a questionnaire. After all subjects were tested, the eradication rates, adverse reaction rates and patient compliance of each group were calculated.
Patients were evaluated at 4 visits: screening (10-30 days before the baseline visit), baseline, end of treatment/efficacy (14 days after the baseline visit) and follow-up (8 weeks after treatment completion). Patients were diagnosed with one (or more) of three validated methods, 13C-urea breath test, rapid urease test or histology, depending on the clinical situation of the patient. Eradication confirmation test was also performed following standard recommendations: 13C-urea breath test at 8 weeks after treatment.
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
- Double (Participant, Care Provider)
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
- •Patients aged 18-
- •Patients with H. pylori infection (Positive for rapid urease test or 13C/14C-urea breath test).
- •Patients who have did not receive H. pylori eradication treatment before.
排除标准
- •Patients with serious underlying diseases, such as liver insufficiency (Aspartate aminotransferase or alanine aminotransferase greater than 1.5 times the normal value), renal insufficiency (Cr≥2.0mg/dL or glomerular filtration rate <50 ml/min), immunosuppression, malignant tumors, Coronary heart disease or coronary artery stenosis ≥75%.
- •Patients who are pregnant or lactating or unwilling to take contraceptive measures during the trial.
- •Patients with active gastrointestinal bleeding.
- •Patients with a history of upper gastrointestinal surgery.
- •Patients allergic to treatment drugs.
- •Patients with medication history of bismuth agents, antibiotics, proton pump inhibitor and other drugs which might influence gut microbiota within 3 months.
- •Patients with other behaviors that may increase the risk of illness, such as alcohol and drug abuse.
- •Patients who are unwilling or incapable to provide informed consents.
结局指标
主要结局
Gut microbiota
时间窗: Week 0, week 2 and week 10
Stool samples were collected at wk0, wk2, and wk10. Patients were instructed to collect stool samples at the medical visit site by using disposable sterile feces collection tubes. Samples were stored at -80℃ after collection immediately. In this study, the influences of antibiotics and combination of probiotics on gut microbiota during H. pylori treatments were investigated using high-throughput sequencing of the 16S rRNA gene.
次要结局
- Rate of adverse reactions(Week 2 and week 10)
- Patient compliance(Week 10)