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

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Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

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

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Authors and Affiliations

  1. Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India

    Uday C. Ghoshal, Deepakshi Srivastava & Asha Misra

Authors
  1. Uday C. Ghoshal
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  2. Deepakshi Srivastava
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  3. Asha Misra
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Correspondence to Uday C. Ghoshal.

Ethics declarations

The study protocol was approved by the Institutional Ethics Committee.

Conflict of interest

UCG, DS, and AM declare that they have no conflict of interest.

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The authors declare that the study was performed in a manner conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

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Ghoshal, U.C., Srivastava, D. & Misra, A. A randomized double-blind placebo-controlled trial showing rifaximin to improve constipation by reducing methane production and accelerating colon transit: A pilot study. Indian J Gastroenterol 37, 416–423 (2018). https://doi.org/10.1007/s12664-018-0901-6

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  • DOI: https://doi.org/10.1007/s12664-018-0901-6

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