ROME Update UEGW Rome Faculty Douglas Drossman, MD University of - PowerPoint PPT Presentation

ROME Update UEGW

Rome Faculty Douglas Drossman, MD University of North Carolina Drossman Gastroenterology PLLC Chapel Hill, NC Lin Chang, MD David Geffen School of Medicine at UCLA Los Angeles, CA William Chey, MD University of Michigan Ann Arbor, MI

Rome Faculty Disclosures Douglas Drossman, MD Nothing to disclose Lin Chang, MD Advisory Board Membership: Salix, QOL Medical, Takeda, Ironwood, Allergan, Commonwealth Labs, Astra Zeneca, Ardelyx William Chey, MD Grants/Research Support: Ironwood, Perrigo, Prometheus, Nestle Consultant/Speaker Bureau: Ardelyx, Astra-Zeneca, Albivro, Actoris, Ironwood Honorarium Recipient: Ardelyx, Astra-Zeneca, Albivro, Actoris, Ironwood

Planning Committee Julie Messick Nothing to disclose

This Program is Supported by Educational Grants from: Prometheus Laboratories Inc., Ferring Pharmaceuticals Inc., Salix, a division of Valeant Pharmaceuticals North America LLC., Ironwood Pharmaceuticals, Inc. 5

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How Does Psyllium Really Work in Constipation? A Double-Blind Crossover Study to Evaluate Its Impact on Magnetic Resonance Imaging Biomarkers K. Murray, G. Major, C. Hoad1, A. Nowak, L. Marciani, A. Silos-Santiago, C. Kurtz, J. Johnston, P. Gowland, R. Spiller, on behalf of the University of Nottingham GI MRI Research Group

Aims and Methods Aims • To assess the effect of psyllium on MRI imaging biomarkers Methods • Double-blind crossover study of adults with functional constipation or IBS-C by Rome III criteria • Patients randomized to Metamucil Original Coarse Fiber 14 g TID (21 g/day) or placebo comparator (maltodextrin 14 g TID) – Treatment periods were preceded by 10 days of usual laxatives, then 8 days without therapy • Patients swallowed 5 MRI transit markers at 0800 on Day 5 of treatment • On Day 6, MRI scans were taken fasting and serially after a standard test meal for 7 hours, with a final fasting scan on Day 7 of treatment • Primary endpoint was the Weighted Average Position Score of transit markers 24 hours after ingestion (WAPS24) (score increases with longer whole gut transit) • Secondary endpoints – Free water content of the small bowel (SBWC) and ascending colon (ACWC) – T 1 and T 2 values of the chyme in the ascending colon (AC) and descending colon (DC) – Colonic volume (CV) Murray K et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP059.

Results • 16 subjects completed both treatment periods Postprandial SBWC • Psyllium accelerated WGT such that WAPS24 decreased by mean 0.8 (1.8, P <0.001* P =0.05, 1-tailed), or 24% 100 • Increase in SBWC was followed by a Postprandial SBWC, mL 81.5 80 smaller increase in ACWC ( P <0.05) 60 • Fasting T1 values were lower than 32.9 40 previously reported in healthy volunteers, but increased on psyllium in both the AC 20 ( P <0.001) and DC ( P <0.01) to values 0 Maltodextrin Psyllium within the normal range • CV increased by 332mL (95%CI 214 – 451, P <0.001), or 48% * All analyses by paired t-test. AC, ascending colon; CV, colonic volume; DC, descending colon; SBWC, small bowel water content; WAPS, Weighted Average Position Score of transit markers 24 hours after ingestion. Murray K et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP059.

Results Effect of Psyllium on Key MRI Parameters Patients with Patients with constipation on constipation on Healthy volunteers* maltodextrin psyllium WAPS24 0.8 (0 – 1.6) 3.4 (1.6-4.8) 2.2 (1.5-3.0) Colonic volume (mL) 561 (239) 690 (218) 1022 (240) T 1 AC (secs) 0.77 (0.64-0.92) 0.55 (0.49-0.61) 0.82 (0.44-1.14) T 1 DC (secs) 0.55 (0.39-0.85) 0.23 (0.19-0.55) 0.57 (0.32-0.78) *Values from previous studies of healthy volunteers. AC, ascending colon; CV, colonic volume; DC, descending colon; SBWC, small bowel water content; WAPS, Weighted Average Position Score of transit markers 24 hours after ingestion. Murray K et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP059.

Conclusions • Psyllium decreased WGT while both CV and fluidity of the colonic chyme (T 1 ) increased – These measures were different on placebo than prior data in healthy volunteers and demonstrated a significant response to therapy • The sequences used are readily translatable to any MRI scanner in clinical use and are promising as non-invasive biomarkers for the assessment of constipation and the effect of gut modulators CV, colonic volume; WGT, whole gut transit. Murray K et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP059.

Sacral Nerve Stimulation for Refractory Constipation: Preliminary Results of a Multicenter Randomized Cross-over Double- blind Study F. Zerbib, L. Siproudhis, P.-A. Lehur, C. Germain, F. Mion, A.-M. Leroi, B. Coffin, A. Le Sidaner, V. Vitton, C. Bouyssou-Cellier, G. Chene

Aim/Methods Aim • To assess the efficacy of sacral nerve stimulation (SNS) in a multicenter randomized cross-over double blind study Methods • Patients with severe constipation refractory to conservative therapy were included if they had ≥ 2 of the following: i) < 3 BMs/week, ii) straining to evacuate on >25% of attempts, iii) sensation of incomplete evacuation on >25% of occasions • Permanent neurostimulator implantation offered to responders to 3-week temporary stimulation (response defined by number of BMs ≥ 3/week and/or >50% improvement in symptoms • After 2-week washout, patients were randomized in a crossover design to two, 8-week periods of active (ON) or sham (OFF) stimulation separated by 2-week washouts – Patients and investigators were blinded to the stimulation sequence • At the end of the 2 trial periods, all patients were offered active stimulation until the last evaluation at 1 year • Symptoms (Wexner score, Visual Analogic Scale), Quality of Life scale, and tolerability/side effects were assessed before and at the end of each period • Colonic transit time and anorectalmanometry were performed at inclusion and at the end of follow-up Zerbib F et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP060.

Results • 36 patients underwent temporary stimulation – Mean age (SD) 45 (14) years, 33 female – Most (77.8%) had predominant dyschesia • Of 21 (58.3%) responders, 20 received permanent stimulation – Mean age (SD) 44 years (15), 19 female • Stimulator explanted in 3 patients during the study period* • After 1-year follow-up, 55% of implanted patients (n=11) remained responders Median Wexner Scores Response to SNS 40 (ITT analysis) Median Wexner score 80 30 60 55 Response rate, % 60 20 20 15 13.5 40 10 20 0 After 0 Baseline 1 year OFF ON temporary Stimulation period stimulation * Reasons for explantation included infection of the stimulator site (n=2) and lack of efficacy/consent withdrawal (n=1). Zerbib F et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP060.

Conclusions • In patients with refractory constipation who responded to temporary SNS, this randomized double-blind study could not demonstrate any significant effect of active stimulation (ON) compared to absence of stimulation (OFF) • SNS may be a therapeutic option in a small subgroup of patients – Positive response remained 1 year after permanent implantation of the stimulator in 30% of initially-tested patients Zerbib F et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP060.

Bifidobacterium Longum NCC3001 Improves Depression and Reduces Brain Emotional Reactivity in Patients with Irritable Bowel Syndrome (IBS): A Randomized Double-blind, Placebo-controlled Trial M. I. Pinto-Sanchez, G. B. Hall, K. Ghajar, A. Nardelli, C. Bolino, C. Welsh, A. Rieder, J. Traynor, C. Gregory, J. Lau, A. C. Ford, G.E. Bergonzelli, M. Surette, S. Collins, P. Moayyedi, P. Bercik

Aim/Methods Aim • To evaluate the effects of B. longum NCC3001 on anxiety and depression in patients with IBS and to study the underlying mechanisms Methods • Randomized, double-blind, placebo-controlled, single center study in adult patients with IBS with diarrhea or mixed stool pattern (Rome III criteria) and mild to moderate anxiety and/or depression • B. longum or placebo (maltodextrin) was administered daily for 6 weeks • Validated questionnaires were used to assess anxiety and depression (HAD score, STAI), IBS symptoms (adequate relief question, IBS Birmingham and Bristol scale), quality of life (SF-36) and somatization (PHQ-15) before, at the end and 1 month after the treatment (follow-up) • Brain activation patterns assessed with backward masked fear paradigm (fMRI), cognitive function (memory and concentration), serum BDNF and inflammatory markers, and gut microbiota profiles (16S rRNA Illumina) Pinto-Sanchez MI et al. UEGW 2015. October 24-28, 2015; Barcelona, Spain: Abstract OP162.