Rifaximin Treatment in Bloating Predominant Functional Bowel Disorders

Phase 3Not Yet RecruitingNCT07522255

Mahidol University78 enrolled

Overview

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.

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.

Study Type

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 3-5. * Colonoscopy, CT colonography, or barium enema performed if clinically indicated as part of standard evaluation for bowel symptoms. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Bloating responder rate

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.