The Effect of Rifaximin Treatment in Bloating Predominant Functional Bowel Disorders: A Randomized Double-blind Placebo-Controlled Trial With Gut Microbiota and Intestinal Gas Analysis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Bloating responder rate
研究概览
简要总结
This randomized, double-blind, placebo-controlled trial will evaluate whether a 14-day course of rifaximin improves bloating in adult patients with Rome IV functional bowel disorders in whom bloating is the predominant symptom. Eligible participants with irritable bowel syndrome, functional constipation, or functional abdominal bloating/distension and bothersome bloating despite adequate bowel movement management will be assigned in a 1:1 ratio to rifaximin 550 mg three times daily or matching placebo for 2 weeks. The primary endpoint is the proportion of participants with bloating response, defined as at least a 1-point reduction from baseline in a 7-point Likert bloating score at the end of treatment.
详细描述
Abdominal bloating is a common and bothersome symptom in disorders of gut-brain interaction, especially irritable bowel syndrome (IBS), functional constipation (FC), and functional abdominal bloating/distension (FAB/D). Current treatment options provide inconsistent benefit, in part because bloating is likely mediated by multiple mechanisms, including altered motility, visceral hypersensitivity, abnormal fermentation, and intestinal microbiota alterations.
Rifaximin is a minimally absorbed oral antibiotic with microbiota-modulating and anti-inflammatory effects. It is effective for IBS with diarrhea and has shown benefit for bloating in prior randomized studies and meta-analyses, but data focused specifically on bloating-predominant functional bowel disorders across Rome IV subgroups remain limited. This trial is designed to test whether rifaximin improves bloating symptoms beyond placebo in a broader population with bloating-predominant functional bowel disorders.
Participants will be randomized in blocks of 4, with stratification by functional bowel disorder subgroup, to receive rifaximin or matching placebo for 14 days in a double-blind parallel-group design. Baseline and post-treatment assessments will include symptom severity, bowel habits, disease-specific quality of life, psychological symptom scores, stool microbiota profiling using 16S rRNA sequencing, and lactulose hydrogen/methane breath testing. Rescue medications will be permitted for breakthrough symptoms and recorded in a daily diary.
The study will evaluate both symptom efficacy and mechanistic outcomes. In addition to the primary bloating responder endpoint, prespecified analyses will assess abdominal pain, disease-specific symptom scales, bowel movement frequency, Bristol Stool Form Scale, quality-of-life measures, psychiatric symptoms, treatment satisfaction, stool microbiota changes, breath test gas production, rescue medication use, and baseline factors associated with treatment response.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 80 years.
- •Rome IV diagnosis of irritable bowel syndrome, functional constipation, or functional abdominal bloating/distension.
- •Bothersome bloating with baseline severity of at least 3 on a 7-point Likert scale after adequate constipation treatment, defined as stool frequency from at least 3 times/week to 3 times/day and Bristol Stool Form Scale type 3-
- •Colonoscopy, CT colonography, or barium enema performed if clinically indicated as part of standard evaluation for bowel symptoms.
排除标准
- •History of major gastrointestinal surgery, except appendectomy or laparoscopic cholecystectomy.
- •Inflammatory bowel disease or other inflammatory gastrointestinal conditions.
- •Current use of, or inability to discontinue, medications that may affect intestinal microbiota or gas measurements, including antibiotics, proton pump inhibitors, probiotics, lactulose, NSAIDs, or metformin.
- •Current use of, or inability to discontinue, medications that may affect bloating symptoms, including simethicone, simethicone-containing antispasmodics, or antidiarrheal medications.
- •Underlying conditions known to affect intestinal microbiota composition, including cirrhosis, uncontrolled diabetes mellitus, end-stage renal disease, obesity, malignancy, or psychiatric disorders.
- •Opioid-induced constipation.
- •Known allergy to rifaximin.
研究组 & 干预措施
Placebo
Participants randomized to this arm receive an identical placebo orally three times daily for 2 weeks.
干预措施: Placebo (Drug)
Rifaximin
Participants randomized to this arm receive rifaximin 550 mg orally three times daily for 2 weeks.
干预措施: Rifaximin (drug) (Drug)
结局指标
主要结局
Bloating responder rate
时间窗: From enrollment to the end of treatment at 2 weeks
Bloating responder is defined as at least a 1-point reduction from baseline to week 2 in bloating symptom severity measured using a 7-point Likert scale for bothersomeness of bloating (range 0 to 6; higher scores indicate worse symptoms). Score categories are 0 = not at all, 1 = hardly, 2 = somewhat, 3 = moderately, 4 = a good deal, 5 = a great deal, and 6 = a very great deal.
次要结局
- Abdominal pain response rate(From enrollment to the end of treatment at 2 weeks)
- Change in Global IBS Symptoms (IBS patients)(From enrollment to the end of treatment at 2 weeks)
- Change in global constipation symptoms (constipation patients)(From enrollment to the end of treatment at 2 weeks)
- Treatment satisfaction(End of treatment at 2 weeks)
- Change in Psychological Symptoms(From enrollment to the end of treatment at 2 weeks)
- Change in Quality of Life (IBS patients)(From enrollment to the end of treatment at 2 weeks)
- Change in Quality of Life (constipation patients)(From enrollment to the end of treatment at 2 weeks)
- Change in quality of life (FAB/D patients)(From enrollment to the end of treatment at 2 weeks)
- Adverse events(From enrollment to the end of treatment at 2 weeks)
- Stool microbiota diversity and composition(From enrollment to the end of treatment at 2 weeks)
- Change in intestinal gas measurement (hydrogen)(From enrollment to the end of treatment at 2 weeks)
- Change in intestinal gas measurement (methane)(From enrollment to the end of treatment at 2 weeks)
- Proportion of patients with positive lactulose hydrogen breath test(From enrollment to the end of treatment at 2 weeks)
- Rescue medication use(From enrollment to the end of treatment at 2 weeks)
- Association between baseline bloating symptom severity score and bloating response at 2 weeks(Baseline predictor with treatment response assessed at 2 weeks)
- Association between baseline fecal microbiota alpha diversity and bloating response at 2 weeks(Baseline predictor with treatment response assessed at 2 weeks)
- Association between baseline positive diagnosis of small intestinal bacterial overgrowth and bloating response at 2 weeks(Baseline predictor with treatment response assessed at 2 weeks.)
- Association between baseline positive diagnosis of intestinal methanogen overgrowth and bloating response at 2 weeks(Baseline predictor with treatment response assessed at 2 weeks.)