Rifaximin Treatment in Bloating Predominant Functional Bowel Disorders

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Rifaximin (drug)
  Participants randomized to this arm receive rifaximin 550 mg orally three times daily for 2 weeks. Allocation is randomized and double-blinded.
• Препарат Placebo
  Matching placebo administered orally three times daily for 14 days.

Первичные конечные точки

• Bloating responder rate [Срок оценки: From enrollment to the end of treatment at 2 weeks]

Вторичные конечные точки (12)

• Abdominal pain response rate [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in Global IBS Symptoms (IBS patients) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in global constipation symptoms (constipation patients) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Treatment satisfaction [Срок оценки: End of treatment at 2 weeks]
• Change in Psychological Symptoms [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in Quality of Life (IBS patients) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in Quality of Life (constipation patients) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in quality of life (FAB/D patients) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Stool microbiota diversity and composition [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in intestinal gas measurement (hydrogen) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Change in intestinal gas measurement (methane) [Срок оценки: From enrollment to the end of treatment at 2 weeks]
• Proportion of patients with positive lactulose hydrogen breath test [Срок оценки: From enrollment to the end of treatment at 2 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Таиланд · 1 центр

• Faculty of Medicine Siriraj Hospital, Mahidol University — Bangkok Noi

Публикации

• Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031. Online ahead of print. PMID 27144627
• Lacy BE, Chang L, Rao SSC, Heimanson Z, Sayuk GS. Rifaximin Treatment for Individual and Multiple Symptoms of Irritable Bowel Syndrome With Diarrhea: An Analysis Using New End Points. Clin Ther. 2023 Mar;45(3):198-209. doi: 10.1016/j.clinthera.2023.01.010. Epub 2023 Mar 14. PMID 36922331
• Chey WD, Shah ED, DuPont HL. Mechanism of action and therapeutic benefit of rifaximin in patients with irritable bowel syndrome: a narrative review. Ther Adv Gastroenterol. 2020 Jan 23;13:1756284819897531. doi: 10.1177/1756284819897531. eCollection 2020. PMID 32047534
• Melchior C, Hammer H, Bor S, Barba E, Horvat IB, Celebi A, Drug V, Dumitrascu D, Kalkan IH, Hauser G, Lionis C, Livovsky D, Mari A, Mulak A, Surdea-Blaga T, Tack J, Vanuytsel T, Savarino EV, Zarate-Lopez N, Hammer J, Dickman R. European Consensus on Functional Bloating and Abdominal Distension-An ESNM/UEG Recommendations for Clinical Management. United European Gastroenterol J. 2025 Nov;13(9):1613 PMID 40844856
• Moshiree B, Drossman D, Shaukat A. AGA Clinical Practice Update on Evaluation and Management of Belching, Abdominal Bloating, and Distention: Expert Review. Gastroenterology. 2023 Sep;165(3):791-800.e3. doi: 10.1053/j.gastro.2023.04.039. Epub 2023 Jul 13. PMID 37452811
• Arora U, Sachdeva K, Garg P, Baitha U, Kedia S, Kalaivani M, Ahuja V, Kumar A, Ranjan P, Vikram NK, Sinha S, Biswas A, Wig N. Efficacy of Rifaximin in Patients With Abdominal Bloating or Distension: A Systematic Review and Meta-analysis. J Clin Gastroenterol. 2024 Apr 1;58(4):360-369. doi: 10.1097/MCG.0000000000001872. PMID 37310270

Идентификаторы

NCT: NCT07522255 · Si 917/2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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