Dataset Information

Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea.

ABSTRACT: OBJECTIVES:The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined. METHODS:Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was conducted before (day 1) and after (day 14) therapy (breath samples obtained every 15 minutes; up to 240 minutes). Patient response (decrease from baseline of ?30% in abdominal pain and ?50% decrease in frequency of mushy/watery stool), symptom improvement, and the relationship of clinical outcomes to LBT results were assessed. RESULTS:A total of 93 patients were included; 62 (66.7%) had positive baseline LBT results. Overall, 48.4% (45/93) of patients responded to rifaximin; of these, 59.7% (37/62) had a positive baseline LBT vs 25.8% (8/31) with a negative LBT (P = 0.002; odds ratio 4.3, 95% confidence interval, 1.5-12.7). Patients with a positive baseline LBT result experienced significantly greater improvement from baseline in 6 of 7 individual IBS symptoms. LBT results after rifaximin therapy did not correlate with clinical response in the 86 patients with evaluable breath tests (P = 0.21); however, patients whose LBT results normalized after rifaximin had the highest response rate of 76.5% (13/17). DISCUSSION:A positive baseline LBT result predicted a higher likelihood of response to rifaximin in IBS-D, suggesting a gut microbiome modulatory mechanism of action for rifaximin.

SUBMITTER: Rezaie A

PROVIDER: S-EPMC6903366 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea.

Rezaie Ali A Heimanson Zeev Z McCallum Richard R Pimentel Mark M

The American journal of gastroenterology 20191201 12

<h4>Objectives</h4>The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined.<h4>Methods</h4>Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was co ...[more]

PMID: 31688023

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Project description:Background & aimsIncreasing drug prices lead to payer coverage restrictions, which limit access to therapy. We assessed the cost effectiveness of rifaximin in management of patients with irritable bowel syndrome with diarrhea (IBS-D) under common payer coverage restrictions and determined the maximum price at which rifaximin would be cost effective using contemporary cost-effectiveness thresholds.MethodsA decision analytic model was constructed to evaluate quality of life, cost, and cost effectiveness of rifaximin for patients with IBS-D and complete noncoverage (insurer pays none of the drug cost), unrestricted access (insurer pays 100% of the drug cost), and formulary-restricted access (insurer pays 100% of the drug cost after for patients failed by initial therapy). The maximum cost-effective drug price was determined for each level of drug coverage using threshold analysis adjusted for willingness to pay thresholds from $50,000 to $150,000 per quality-adjusted life year (QALY). Analysis was performed from a payer perspective with a 1-year time horizon.ResultsUnrestricted and formulary-restricted access were more effective than complete non-coverage, resulting in additional 0.03 and 0.05 QALYs gained over noncoverage. However, unrestricted and formulary-restricted coverage were more expensive. At current drug prices, unrestricted or formulary-restricted coverage would cost an additional $1,207,136 or $171,850/QALY gained, compared to complete non-coverage. A 12% to 62% price reduction ($18.46 to $26.34/pill) for formulary-restricted access and 84% to 88% price reduction ($3.53 to $4.71/pill) for unrestricted access would be needed for rifaximin to be a cost-effective treatment strategy. Rifaximin retreatment intervals, response rates, and adverse events were important factors in sensitivity analysis.ConclusionUsing a decision analytic model, we show that payer coverage for rifaximin for patients with IBS-D exceeds generally accepted cost-effectiveness thresholds at current drug prices. Improved payer coverage could be justified using value-based pricing methods.

Project description:BackgroundPrevious studies have indicated that ramosetron, a 5-hydroxytryptamine-3 receptor antagonist, achieves global improvement in irritable bowel syndrome (IBS) symptoms in male patients with IBS with diarrhea (IBS-D). However, in addition to global assessment it was deemed important to assess "clinically meaningful improvements, focusing on the patient's chief complaint and the severity of major IBS symptoms". We performed a randomized, placebo-controlled, phase IV pilot study to explore and examine efficacy variables that allow such evaluation of ramosetron in male patients with IBS-D.MethodsWe performed a prospective study of 115 male outpatients with IBS-D (according to the Rome III criteria), from June 2009 to December 2009 at 25 centers in Japan. After a one-week baseline period, subjects received either 5 μg of ramosetron (n = 47) or placebo (n = 51) once daily for 12 weeks. To evaluate "clinically meaningful improvements focusing on the severity of major IBS symptoms," the Japanese version of the IBS severity index (IBSSI-J) was used.ResultsChange in IBSSI-J overall score from baseline was -133.5 ± 110.72 in the ramosetron 5 μg group and -108.2 ± 94.44 in the placebo group (P = 0.228) at the last evaluation point. Differences in responder rates for at least a 50% reduction from baseline in IBSSI-J between the ramosetron 5 μg group and the placebo group were over 10%, except Month 1. The monthly responder rate for global assessment of relief of overall IBS symptoms in the ramosetron 5 μg group showed a statistically significant improvement compared to placebo at the second month (44.4% vs 18.4%, P = 0.012). The proportion of patients who had a ≥ 50% reduction in IBSSI-J overall score was 24/37 (64.9%) in the responder group on global assessment and 18/54 (33.3%) in the non-responder group at Week 12.ConclusionsFurther examination will be needed before IBSSI-J can be used in clinical trials of agents for IBS-D. However, this study revealed that response on global assessment was correlated with improvement in the IBSSI-J, suggesting that global assessment reflects improvement of the symptom severity of patients with IBS-D. (Clinicaltrials.gov ID: NCT00918411 Registered 9 June 2009).

Project description:ObjectiveFructose malabsorption is a common digestive disorder in which absorption of fructose in the small intestine is impaired. An abnormality of the main intestinal fructose transporter proteins has been proposed as a cause for fructose malabsorption. However the underlying molecular mechanism for this remains unclear. In this study, we investigated whether carbohydrate response element-binding protein (ChREBP) plays a role in intestinal fructose absorption through the regulation of genes involved in fructose transport and metabolism and ion transport.MethodsWild type (WT) and Chrebp knockout (KO) mice (6 or 8 weeks old) were fed a control diet (55% starch, 15% maltodextrin 10) or high-fructose diet (HFrD, 60% fructose, 10% starch) for 3-12 days. Body weight and food intake were measured, signs of fructose malabsorption were monitored, and the expression of genes involved in fructose transport/metabolism and ion transport was evaluated. Furthermore, transient transfection and chromatin immunoprecipitation were performed to show the direct interaction between ChREBP and carbohydrate response elements in the promoter of Slc2A5, which encodes the fructose transporter GLUT5.ResultsChrebp KO mice fed the control diet maintained a constant body weight, whereas those fed a HFrD showed significant weight loss within 3-5 days. In addition, Chrebp KO mice fed the HFrD exhibited a markedly distended cecum and proximal colon containing both fluid and gas, suggesting incomplete fructose absorption. Fructose-induced increases of genes involved in fructose transport (GLUT5), fructose metabolism (fructokinase, aldolase B, triokinase, and lactate dehydrogenase), and gluconeogenesis (glucose-6-phosphatase and fructose-1,6-bisphosphatase) were observed in the intestine of WT but not of Chrebp KO mice. Moreover the Na+/H+ exchanger NHE3, which is involved in Na+ and water absorption in the intestine, was significantly decreased in HFrD-fed Chrebp KO mice. Consistent with this finding, the high-fructose diet-fed Chrebp KO mice developed severe diarrhea. Results of chromatin immunoprecipitation assays showed a direct interaction of ChREBP with the Glut5 promoter, but not the Nhe3 promoter, in the small intestine. Ectopic co-expression of ChREBP and its heterodimer partner Max-like protein X activated the Glut5 promoter in Caco-2BBE cells.ConclusionsChREBP plays a key role in the dietary fructose transport as well as conversion into lactate and glucose through direct transcriptional control of genes involved in fructose transport, fructolysis, and gluconeogenesis. Moreover, ablation of Chrebp results in a severe diarrhea in mice fed a high-fructose diet, which is associated with the insufficient induction of GLUT5 in the intestine.

Project description:Altered gut microbiota are assumed to be involved in the pathogenesis of irritable bowel syndrome (IBS). However, gut microbiota alterations reported in different studies are divergent and sometimes even contradictory. To better elucidate the relationship between altered gut microbiota and IBS, we characterized fecal microbiota of diarrhea-predominant IBS (IBS-D) patients and further explored the effect of rifaximin on gut microbiota using bacterial 16S rRNA gene-targeted pyrosequencing. In our study, IBS-D patients defined by Rome III criteria and age-and-gender matched healthy controls (HC) were enrolled to investigate the fecal microbiota alterations. These IBS-D patients were then treated with rifaximin for 2 weeks and followed up for 10 weeks. Fecal microbiota alterations, small intestine bacterial overgrowth (SIBO) and gastrointestinal (GI) symptoms of IBS-D patients were analyzed before and after treatment. Our results showed fecal microbiota richness but not diversity was decreased in IBS-D patients as compared to HC and there were alterations of fecal microbiota at different taxonomy levels. The abundant phyla Firmicutes was significantly decreased and Bacteroidetes was increased in IBS-D patients. Moreover, the alterations of predominant fermenting bacteria such as Bacteroidales and Clostridiales might be involved in the pathophysiology of IBS-D. In addition, rifaximin was effective in terms of SIBO eradication and even GI symptoms of IBS-D patients achieved at least 10-week improvement after treatment. Furthermore, rifaximin induced alterations of some special bacteria rather than affected the overall composition of microbiota in IBS-D patients. Meanwhile, a potential decrease in propanoate and butanoate metabolism was found in these IBS-D patients after rifaximin treatment. Taken together, there were alterations of gut microbiota in IBS-D patients as compared to HC. Rifaximin could relieve GI symptoms, modify gut microbiota in IBS-D patients and eradicate SIBO in those patients with SIBO, suggesting an additional therapeutic mechanism of rifaximin in the treatment of IBS-D. Our findings of compositional gut microbiota alterations in IBS-D and the effect of rifaximin on the gut microbiota implied that altered gut microbiota were associated with the pathogenesis of IBS.

Project description:BackgroundProbiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D); however, the certainty of evidence is low. Well-powered randomized controlled dose-ranging trials are warranted on promising single-strain candidates.AimTo investigate the clinical efficacy of Lactiplantibacillus plantarum (L. plantarum) Lpla33 (DSM34428) in adults with IBS-D.MethodsThis is a randomized, double-blind, placebo-controlled, multi-center, and dose-ranging study. Three hundred and seven adults, 18-70 years of age, with IBS-D, according to Rome IV criteria, were allocated (1:1:1) to receive placebo or L. plantarum Lpla33 at 1 × 109 (1B) or 1 × 1010 (10B) colony-forming units/d over an 8-wk intervention period. The primary outcome was the change in IBS severity scoring system (IBS-SSS) total score after 8 wk, while secondary and exploratory outcomes included abdominal pain severity, IBS related quality of life, stool and microbial profile, and perceived stress.ResultsIBS-SSS was significantly reduced, after 8 wk, in participants receiving L. plantarum 1B (-128.45 ± 83.30; P < 0.001) and L. plantarum 10B (-156.77 ± 99.06; P < 0.001), compared to placebo (-58.82 ± 74.75). Further, a dose-ranging effect was observed, with a greater absolute reduction in the L. plantarum 10B group (P < 0.05). A reduction in sub-scores related to abdominal pain, abdominal distension, bowel habits, and quality of life was observed in both L. plantarum groups compared to placebo (P < 0.001). Further, 62.5% and 88.4% of participants administered L. plantarum 1B and 10B, respectively, were classified as stool consistency responders based on a reduction in diarrheal stool form, as compared to 26.3% in the placebo group (P < 0.001). In contrast, no significant shifts were observed in microbial diversity.ConclusionL. plantarum Lpla33 (DSM34428) is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.

Dataset Information

Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea.

Publications

Lactulose Breath Testing as a Predictor of Response to Rifaximin in Patients With Irritable Bowel Syndrome With Diarrhea.

Similar Datasets

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