Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome
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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.
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.
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).
Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.
KeywordsGulf War illness Diarrhea Rifaximin Irritable bowel syndrome Veterans
The authors thank Dr. Keith G. Tolman, M.D. for assistance in editing the initial proposal and periodic consultation. The study drug and placebo tablets were provided by Salix Pharmaceuticals.
AKT received grant support from the Department of Veterans Affairs and the Department of Defense (W81XWH-10-1-0593, W81XWH-15-1-0636). GNV received support from the Department of Veterans Affairs (1I01CX001477-01) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK099052).
Compliance with ethical standards
Conflict of interest
AKT has received funding from Shire and Synergy Pharmaceuticals. NJT Grant/Research Support: Rome Foundation; Abbott Pharmaceuticals; Datapharm; Pfizer; Salix [Irritable bowel syndrome]; Prometheus Laboratories Inc [Irritable bowel syndrome (IBS Diagnostic)]; Janssen [Constipation]. Consultant/Advisory Boards: Adelphi Values [Functional dyspepsia (patient-reported outcome measures)]; (Budesonide)]; GI therapies [Chronic constipation (Rhythm IC)]; Sax Institute; Allergens PLC; Napo Pharmaceutical; Outpost Medicine; Samsung Bioepis; Yuhan [IBS]; Synergy [IBS]; Theravance [Gastroparesis]; Patent Holder: Biomarkers of irritable bowel syndrome [Irritable bowel syndrome] Licensing Questionnaires [Mayo Clinic Talley Bowel Disease Questionnaire—Mayo Dysphagia Questionnaire]; Nestec European Patent [Application No. 12735358.9]; Singapore “Provisional” Patent [NTU Ref: TD/129/17 “Microbiota Modulation Of BDNF Tissue Repair Pathway”].
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