Bloating, Rifaximin, Functional Bowel Disorder, Irritable Bowel Syndrome, Constipation
Conditions
Keywords
Rifaximin, Bloating, Functional bowel disorder
Brief summary
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.
Detailed description
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.
Interventions
DRUGRifaximin (drug)
Participants randomized to this arm receive rifaximin 550 mg orally three times daily for 2 weeks. Allocation is randomized and double-blinded.
DRUGPlacebo
Matching placebo administered orally three times daily for 14 days.
Sponsors
Mahidol University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bloating responder rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal pain response rate | From enrollment to the end of treatment at 2 weeks | Abdominal pain responder is defined as at least a 1-point reduction from baseline to week 2 in abdominal pain severity measured using a 7-point Likert scale for bothersomeness of abdominal pain (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. |
| Change in Global IBS Symptoms (IBS patients) | From enrollment to the end of treatment at 2 weeks | Change in IBS Symptom Severity Score (IBS-SSS) from baseline, assessing overall IBS symptom burden, abdominal pain, bloating, and bowel habit changes. The IBS-SSS scale ranges from 0 to 500, with higher scores indicating more severe IBS symptoms. |
| Change in global constipation symptoms (constipation patients) | From enrollment to the end of treatment at 2 weeks | Change in Patient Assessment of Constipation-Symptoms (PAC-SYM) score, evaluating constipation-related symptoms, including stool consistency, discomfort, and straining. The PAC-SYM scale ranges from 0 to 48, with higher scores indicating worse constipation symptoms. |
| Treatment satisfaction | End of treatment at 2 weeks | Overall treatment satisfaction, measured using a Visual Analog Scale (VAS) ranging from 0 to 10: 0 = Completely Dissatisfied 10 = Completely Satisfied Higher scores indicate greater satisfaction with treatment. The difference between baseline and post-intervention scores will be analyzed. |
| Change in Psychological Symptoms | From enrollment to the end of treatment at 2 weeks | Change in Depression, Anxiety, and Stress Scores (DASS-21), a validated self-reported scale measuring psychological distress. The DASS-21 consists of three subscales: Depression (0-21) Anxiety (0-21) Stress (0-21) Each subscale score ranges from 0 (normal) to 21 (severe symptoms), with higher scores indicating greater psychological distress. The total score is calculated by summing individual subscale scores. |
| Change in Quality of Life (IBS patients) | From enrollment to the end of treatment at 2 weeks | Change in IBS-specific Quality of Life (IBS-QoL) score, which assesses the impact of IBS on daily activities, emotional well-being, and social functioning. The IBS-QoL score ranges from 0 to 100, with higher scores indicating better quality of life. |
| Change in Quality of Life (constipation patients) | From enrollment to the end of treatment at 2 weeks | Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL). The PAC-QoL is a 28-item patient-reported questionnaire assessing constipation-related quality of life over the previous 2 weeks. The overall score is typically reported as the mean item score and ranges from 0 to 4, with higher scores indicating worse constipation-related quality of life. |
| Change in quality of life (FAB/D patients) | From enrollment to the end of treatment at 2 weeks | The quality of life of patients with FAB/D was measure with 36-Item Short Form Health Survey (SF-36). The SF-36 assesses health-related quality of life across 8 domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. Each domain score is transformed to a 0 to 100 scale, with higher scores indicating better health status. |
| Stool microbiota diversity and composition | From enrollment to the end of treatment at 2 weeks | Change from baseline in stool microbiota alpha diversity, beta diversity, and taxonomic abundance measured by 16S rRNA sequencing. |
| Change in intestinal gas measurement (hydrogen) | From enrollment to the end of treatment at 2 weeks | Change from baseline in hydrogen gas production measured in part per million unit during lactulose hydrogen breath testing. |
| Change in intestinal gas measurement (methane) | From enrollment to the end of treatment at 2 weeks | Change from baseline in methane gas production measured in part per million unit during lactulose hydrogen breath testing. |
| Proportion of patients with positive lactulose hydrogen breath test | From enrollment to the end of treatment at 2 weeks | A positive lactulose hydrogen breath test is defined as either a rise in breath hydrogen of 20 ppm or more above baseline within 90 minutes or a breath methane concentration of 10 ppm or more at any time during the test after ingestion of 10 g lactulose. Breath samples are collected every 15 to 30 minutes for up to 180 minutes. Higher proportions indicate a worse outcome (more abnormal breath test results). |
| Rescue medication use | From enrollment to the end of treatment at 2 weeks | Frequency and dose of rescue medications used for breakthrough symptoms during the treatment period. |
| Adverse events | From enrollment to the end of treatment at 2 weeks | Incidence of treatment-emergent adverse events. |
| Association between baseline bloating symptom severity score and bloating response at 2 weeks | Baseline predictor with treatment response assessed at 2 weeks | Exploratory analysis of whether baseline bloating symptom severity predicts treatment response. Baseline bloating symptom severity is assessed using a 7-point Likert scale for bothersomeness of bloating (score range 0 to 6; higher scores indicate worse symptoms). The association between baseline score and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score. |
| Association between baseline fecal microbiota alpha diversity and bloating response at 2 weeks | Baseline predictor with treatment response assessed at 2 weeks | Exploratory analysis of whether baseline fecal microbiota alpha diversity predicts treatment response. Baseline stool microbiota is assessed using 16S rRNA sequencing. Alpha diversity will be assessed using the Shannon diversity index. The association between baseline Shannon diversity index and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score. |
| 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. | Exploratory analysis of whether baseline small intestinal bacterial overgrowth (SIBO) status predicts treatment response. Baseline SIBO status will be assessed using a lactulose hydrogen-methane breath test after ingestion of 10 g lactulose, with breath samples collected every 15 to 30 minutes for up to 180 minutes. A positive SIBO diagnosis is defined as a rise in breath hydrogen of 20 parts per million or more above baseline within 90 minutes. The association between baseline positive SIBO status (yes/no) and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score. |
| Association between baseline positive diagnosis of intestinal methanogen overgrowth and bloating response at 2 weeks | Baseline predictor with treatment response assessed at 2 weeks. | Exploratory analysis of whether baseline intestinal methanogen overgrowth (IMO) status predicts treatment response. Baseline IMO status will be assessed using a lactulose hydrogen-methane breath test after ingestion of 10 g lactulose, with breath samples collected every 15 to 30 minutes for up to 180 minutes. A positive IMO diagnosis is defined as a breath methane concentration of 10 parts per million or more at any time during the test. The association between baseline positive IMO status (yes/no) and bloating responder status at 2 weeks will be evaluated using logistic regression and reported as an odds ratio. Bloating responder is defined as at least a 1-point reduction from baseline in bloating symptom severity score. |
Countries
Thailand
Contacts
CONTACTMonthira Maneerattanaporn, M.D.
CONTACTPubet Weeranawin, M.D.
PRINCIPAL_INVESTIGATORMonthira Maneerattanaporn, M.D.
Mahidol University
STUDY_CHAIRPubet Weeranawin, M.D.
Mahidol University
STUDY_CHAIRSomchai Leelakusolvong, M.D.
Mahidol University
STUDY_CHAIRTanawat Geeratragool, M.D.
Mahidol University
Outcome results
None listed