Cash, Brooks D.

Goal: A novel 5-strain (Bl-04, Bi-07, HN019, NCFM, and Lpc-37) probiotic blend was developed and its safety and efficacy were evaluated in patients with functional gastrointestinal (GI) symptoms. Background: These strains administered together have not previously been investigated. Study: Patients aged 18 to 75 years with functional GI symptoms were eligible for inclusion in a single-arm, open-label, multicenter study (NCT04155801). An oral capsule containing the novel probiotic blend was administered once daily for 30 days. The primary efficacy endpoint was patient-reported improvement in overall GI well-being at day 30. Secondary efficacy endpoints included changes in GI symptoms assessed using the GI Health Symptom Questionnaire. Incidence of treatment-emergent adverse events was recorded at all visits. Results: Of 188 enrolled patients, 72.3% were female and mean (SD) age was 44.1 (13.4) years. At day 30, 85.1% of patients achieved the primary endpoint, a positive response signifying improvement in overall GI well-being. Improvements from baseline were reported at day 30 in diarrhea frequency (baseline frequency≥3 to 4 d/wk) and severity (baseline severity≥5/10) for 75.8% and 87.3% of patients, respectively. Over the same time period, constipation frequency (baseline frequency≥3 to 4 d/wk) and severity (baseline severity≥5/10) improved in 73.6% and 80.4% of patients, respectively. Most patients reported improvements at day 30 in frequency and severity of straining, urgency, abdominal pain/discomfort, bloating, and distention. Improvements reported at day 30 were generally observable at day 14. No safety signals were identified. Conclusion: A novel 5-strain probiotic blend improved functional GI symptoms and was safe.

Background: Eluxadoline, a United States Food and Drug Administration (FDA)-approved treatment for irritable bowel syndrome with diarrhea (IBS-D), underwent a change to its US prescribing information on 21 April 2017, contraindicating it in patients without a gallbladder due to increased risk of pancreatitis. This study aimed to elucidate the potential role of eluxadoline’s label change on the number of reported spontaneous adverse events (AEs) of pancreatitis. Methods: A pharmacovigilance database (Oracle Argus) was searched for eluxadoline use and spontaneously reported pancreatitis cases from 1 January 2016 to 30 June 2018. Pancreatitis cases were reported as a proportion of the total number of reported AE cases in the safety database. The FDA’s adverse event reporting system (AERS) was also interrogated for cases of pancreatitis concomitantly reported with eluxadoline use. Results: In patients who received eluxadoline, 273 reported cases of pancreatitis were recorded (total AEs n = 2191; 12.5%). When known, 28.2% of patients reporting pancreatitis had intact gallbladders (49/174). Eluxadoline was withdrawn in 97.5% of cases, with 87.1% of patients improving or recovered at time of reporting. Importantly, the reporting proportion of pancreatitis cases decreased from 14.4% to 8.9% post label change. Findings were supported by the AERS results, which demonstrated a decrease in reporting proportion from 21.2% to 12.8%. Conclusions: While cautious interpretation is warranted, post-marketing data indicate that the contraindication of eluxadoline in patients without a gallbladder led to reduced reported cases of pancreatitis, with no additional reports of moderately severe or severe cases. Eluxadoline is a safe and well-tolerated treatment option for IBS-D when used according to the label.

Objective Colon capsule endoscopy (CCE) has shown promise for colorectal neoplasia detection compared with optical colonoscopy (OC), but has not been compared with other screening tests in average risk screening patients. Design Patients 50 to 75 years of age (African Americans, 45–75 years) were randomised to CCE or CT colonography (CTC) and subsequent blinded OC. The primary endpoint was diagnostic yield of polyps ≥6 mm with CCE or CTC. Secondary endpoints included accuracy for size and histology, examination completeness, number/proportion of subjects with polyps and adenomas ≥6 mm and ≥10 mm, subject satisfaction and safety. Results From 320 enrolled subjects, data from 286 (89.4%) were evaluable. The proportion of subjects with any polyp ≥6 mm confirmed by OC was 31.6% for CCE versus 8.6% for CTC (pPr non-inferiority and superiority=0.999). The diagnostic yield of polyps ≥10 mm was 13.5% with CCE versus 6.3% with CTC (pPr non-inferiority=0.9954). The sensitivity and specificity of CCE for polyps ≥6 mm was 79.2% and 96.3% while that of CTC was 26.8% and 98.9%. The sensitivity and specificity of CCE for polyps ≥10 mm was 85.7% and 98.2% compared with 50% and 99.1% for CTC. Both tests were well tolerated/safe. Conclusion CCE was superior to CTC for detection of polyps ≥6 mm and non-inferior for identification of polyps ≥10 mm. CCE should be considered comparable or superior to CTC as a colorectal neoplasia screening test, although neither test is as effective as OC. Trial registration number ClinicalTrials.gov no: NCT02754661 .

INTRODUCTION: Bowel preps for colonoscopy can cause transient changes in gut microbiota. Rifaximin is indicated as IBS-D treatment in adults. This post hoc analysis evaluated effect of time since colonoscopy on rifaximin response for IBS-D. METHODS: Two phase 3 studies (TARGET 1/2) comprised adults who had documented history of colonoscopy <2 y prior to enrollment for IBS evaluation; otherwise they had 1 within 30 d of signed consent. Patients (pts) were randomized to rifaximin 550 mg TID or placebo for 2 wks. Responders, grouped by time from colonoscopy to treatment start (≤60 d or >60 d), were analyzed using LOCF. Composite responders (FDA endpoint) were pts meeting weekly response criteria for abdominal pain (≥30% decrease from baseline in mean weekly pain score [range, 0-6]) and stool consistency (≥50% decrease from baseline in d/wk with Bristol Stool Scale type 6/7 stool) during ≥2 of first 4 wks posttreatment; responders for individual components also were determined. RESULTS: Differences in responder rates between rifaximin and placebo were observed in colonoscopy-timing subgroups (≤60 d or >60 d), with largest differences seen in >60 d group (Figure 1). Among pts who had colonoscopy >60 d prior to starting treatment in TARGET 1, a greater percentage treated with rifaximin (n=109) vs placebo (n=106) were composite (47.7% vs 34.0%; P = 0.04), abdominal pain (53.2% vs 40.6%; P = 0.06), or stool consistency (81.7% vs 63.2%; P = 0.002) responders. For colonoscopy ≤60 d prior to starting treatment, a greater percentage of pts treated with rifaximin (n = 199) vs placebo (n = 208) were composite (45.7% vs 40.9%; P = 0.32), abdominal pain (50.3% vs 42.8%; P = 0.13), or stool consistency (77.4% vs 69.7%; P = 0.08) responders. In TARGET 2, a greater percentage of pts treated with rifaximin (n = 106) vs placebo (n = 97) in colonoscopy >60 d prior group were composite (45.3% vs 32.0%; P = 0.05), abdominal pain (53.8% vs 39.2%; P = 0.04), or stool consistency (71.7% vs 61.9%; P = 0.14) responders. A greater percentage of pts treated with rifaximin (n = 209) vs placebo (n = 223) in colonoscopy ≤60 d prior group were responders, although differences were smaller: composite (47.4% vs 38.1%; P = 0.05), abdominal pain (51.7% vs 44.8%; P = 0.16), and stool consistency (75.1% vs 65.5%; P = 0.03). CONCLUSION: Larger differences in responder rates with rifaximin vs placebo were observed in pts in whom colonoscopy was >60 d from start of IBS-D therapy. This may be related in part to reestablishment of IBS-related gut microbiota dysbiosis; further research is needed.

SUMMARY Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

OBJECTIVES: We conducted a randomized, placebo-controlled trial, which evaluated a novel formulation of caraway oil and L-menthol using microsphere-based site-specific targeting (COLM-SST) vs placebo in patients with functional dyspepsia (FD). METHODS: Adult men and women with FD defined by Rome III criteria were recruited. Patients were randomized to COLM-SST (25 mg of caraway oil and 20.75 mg of L-menthol per capsule, at 2 capsules per dose, twice per day) or placebo. Efficacy was measured at 24 hours, 2 weeks, and 4 weeks. Patients were allowed to take concomitant medications for their FD throughout the trial, and rescue medicines were allowed, 48 hours after start of dosing. RESULTS: Ninety-five patients were enrolled (mean age = 43.4 years; 75.8% women). At 24 hours, the active arm reported a statistically significant reduction in postprandial distress syndrome symptoms ( P = 0.039), and a nonsignificant trend toward benefit of epigastric pain syndrome symptoms ( P = 0.074). In patients with more severe symptoms, approximately 3 quarters of patients showed substantial global improvement (i.e., clinical global impressions), after 4 weeks of treatment, vs half in the control arm. These differences were statistically significant for patients with epigastric pain syndrome ( P = 0.046), and trending toward significance for patients with postprandial distress syndrome ( P = 0.091). There was no statistically significant difference between groups for Global Overall Symptom scores for the overall population at 2 and 4 weeks. Treatment emergent adverse events were mild to moderate, and no serious adverse events were reported. DISCUSSION: In patients taking their usual medications for FD, COLM-SST provided rapid relief (within 24 hours) and relief of severe FD symptoms. It was safe and well tolerated.