G Major1, K Murray1,2, G Singh1, A Nowak1, C L Hoad1,2, L Marciani1, A Silos-Santiago3, C B Kurtz3, J M Johnston3, P Gowland1,2, R Spiller1. 1. Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, UK. 2. Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK. 3. Ironwood Pharmaceuticals Inc., Cambridge, MA, USA.
Abstract
BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.
RCT Entities:
BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.
Authors: Sarah Sulaiman; Pavel Gershkovich; Caroline L Hoad; Matthew Calladine; Robin C Spiller; Snow Stolnik; Luca Marciani Journal: Pharmaceutics Date: 2022-01-24 Impact factor: 6.321
Authors: Hayfa Sharif; Caroline L Hoad; Nichola Abrehart; Penny A Gowland; Robin C Spiller; Sian Kirkham; Sabarinathan Loganathan; Michalis Papadopoulos; Marc A Benninga; David Devadason; Luca Marciani Journal: Diagnostics (Basel) Date: 2021-05-28
Authors: David Gunn; Zainab Abbas; Hannah C Harris; Giles Major; Caroline Hoad; Penny Gowland; Luca Marciani; Samantha K Gill; Fred J Warren; Megan Rossi; Jose Maria Remes-Troche; Kevin Whelan; Robin C Spiller Journal: Gut Date: 2021-08-05 Impact factor: 23.059