Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome

Dig Dis Sci. 2019 Mar;64(3):838-845. doi: 10.1007/s10620-018-5344-5. Epub 2018 Oct 28.

Abstract

Background: Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation.

Methods: A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2 weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7 days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7 days, to generate a continuous variable. The symptom data were compared after 2 weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2 weeks of treatment.

Results: Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77 years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54).

Conclusion: Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.

Keywords: Diarrhea; Gulf War illness; Irritable bowel syndrome; Rifaximin; Veterans.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteria / drug effects*
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Breath Tests / methods*
  • Defecation / drug effects
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gulf War*
  • Humans
  • Irritable Bowel Syndrome / diagnosis*
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / microbiology
  • Irritable Bowel Syndrome / physiopathology
  • Lactulose / administration & dosage*
  • Lactulose / metabolism
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Quality of Life
  • Rifaximin / adverse effects
  • Rifaximin / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Veterans*

Substances

  • Anti-Bacterial Agents
  • Lactulose
  • Rifaximin