A randomized double-blind placebo-controlled trial showing rifaximin to improve constipation by reducing methane production and accelerating colon transit: A pilot study

被引:42
作者
Ghoshal U.C. [1 ]
Srivastava D. [1 ]
Misra A. [1 ]
机构
[1] Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow
关键词
Functional constipation; Functional gastrointestinal disorder; Gut microbiota; Irritable bowel syndrome; Lactulose hydrogen breath test; Rifaximin;
D O I
10.1007/s12664-018-0901-6
中图分类号
学科分类号
摘要
Objective: Gut microbe-derived methane may slow colon transit causing chronic constipation (CC). Effect of rifaximin on breath methane and slow-transit CC was evaluated. Method: Bristol stool form, frequency, colon transit time (CTT), and breath methane were evaluated in 23 patients with CC (10 patients with constipation-predominant irritable bowel syndrome [IBS-C], 13 functional constipation, Rome III) and m-ethane production compared with 68 non-constipating IBS. Methane-producing CC (basal ≥ 10 PPM and/or post-lactulose rise by > 10 PPM) was randomized (double-blind) to rifaximin (400-mg thrice/day, 2-weeks) or placebo. Stool forms, frequency, breath methane, and CTT were recorded afterward. Results: CC patients tended to be methane producer more often (13/23 [56.5%] vs. 25/68 [36.5%], p = 0.07) and had greater area under curve (AUC) for methane (2415 [435–23,580] vs. 1335 [0–6562.5], p = 0.02) than non-constipating IBS. Methane producers (8/13 [61.5%]) and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h, 53 [0–60] vs. 19 [8–56], p = 0.06; 60-h, 16 [0–57] vs. 13 [3–56], p = 0.877). Six and 7/13 methane producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.5–23,580] vs. 2617.5 [562.5–19,867.5], p = 0.005) than placebo (3945 [2415–12,952.5] vs. 3720 [502.5–9210], p = 0.118) at 1 month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention, 54 [44–57] vs. 36 [23–60], p = 0.05; 60-h, 45 [3–57] vs. 14 [11–51], p = 0.09) but none on placebo (p = 0.02) (36-h, 31 [0–60] vs. 25 [0–45], p = 0.078; 60-h, 6 [0–54] vs. 12 [0–28], p = 0.2). Weekly stool frequency (3 [1–9] and 7 [1–14], p = 0.05) and forms improved with rifaximin than placebo. Conclusion: Rifaximin improves CC by altering methane production and colon transit. Trial registration: Clinical Trial Registry, India: REF/2012/01/003216 [Figure not available: see fulltext.]. © 2018, Indian Society of Gastroenterology.
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页码:416 / 423
页数:7
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