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Trials
Published in: Trials 1/2013

Open Access 01-12-2013 | Study protocol

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): study protocol for a randomised controlled trial

Authors: Matthew P Leighton, Ching Lam, Samir Mehta, Robin C Spiller

Published in: Trials | Issue 1/2013

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Abstract

Background

Irritable bowel syndrome (IBS) is reported by one in ten of the population accounting for up to 40% of new referrals to gastroenterology outpatients. Patients characteristically have abdominal discomfort and disturbed bowel habit. Diarrhoea-predominant IBS is characterised by frequent loose stools with associated urgency and abdominal cramps. Current symptomatic treatments can reduce bowel frequency but often fail to reduce discomfort.
Mesalazine is an anti-inflammatory drug used to treat patients with inflammatory bowel disease. There is one pilot study suggesting it may be beneficial to patients who have diarrhoea-predominant IBS but these findings need to be confirmed in a larger trial. The current study aims to test the effectiveness of mesalazine to reduce symptoms in diarrhoea-predominant IBS patients. The study will also investigate the mode of action of the drug, especially its impact on mast cell activation.

Methods/design

This is a multicentre randomised, double-blind, placebo-controlled trial using a parallel group design. At least 108 participants with diarrhoea-predominant IBS will be recruited through at least six hospitals. The intervention is a 12-week course of 2g mesalazine granules taken up to twice a day. The comparator is a blinded placebo granule formulation.
Outcome measures include stool diaries, symptom questionnaires, stool and blood samples together with rectal mucosal biopsies. The daily stool diary will record stool frequency and form, urgency, bloating, abdominal pain and a global satisfaction with control of IBS scored each week. The questionnaires will assess bowel symptoms, while the samples and biopsies will be used to analyse underlying mechanisms of any response.
Primary outcome will be the average stool frequency during weeks 11 and 12 of the treatment period and will be compared between treatment arms using an analysis of covariance in the form of a general linear model incorporating baseline characteristics that are thought a priori to strongly predict outcome. The primary efficacy parameter will be the difference in mean frequency between treatment arms.

Discussion

This report describes a randomised controlled trial that will provide evidence of any benefit of treating diarrhoea-predominant IBS patients with mesalazine. The results will be available toward the end of 2013.

Trial registration

ISRCTN76612274
Appendix
Available only for authorised users
Literature
1.
Kroenke K: Physical symptom disorder: a simpler diagnostic category for somatization-spectrum conditions. J Psychosom Res. 2006, 60: 335-339. 10.1016/j.jpsychores.2006.01.022.CrossRefPubMed
2.
Whitehead WE, Crowell MD, Robinson JC, Heller BR, Schuster MM: Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut. 1992, 33: 825-830. 10.1136/gut.33.6.825.CrossRefPubMedPubMedCentral
3.
Santos J, Saperas E, Nogueiras C, Mourelle M, Antolin M, Cadahia A, Malagelada JR: Release of mast cell mediators into the jejunum by cold pain stress in humans. Gastroenterology. 1998, 114: 640-648. 10.1016/S0016-5085(98)70577-3.CrossRefPubMed
4.
Guilarte M, Santos J, de Torres I, Alonso C, Vicario M, Ramos L, Martínez C, Casellas F, Saperas E, Malagelada JR: Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007, 56: 203-209. 10.1136/gut.2006.100594.CrossRefPubMed
5.
Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, Rhee JC: Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006, 21: 71-78. 10.1111/j.1440-1746.2005.04143.x.CrossRefPubMed
6.
Dunlop SP, Jenkins D, Spiller RC: Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Am J Gastroenterol. 2003, 98: 1578-1583. 10.1111/j.1572-0241.2003.07542.x.CrossRefPubMed
7.
Aron J: Response to mesalamine and balsalazide in patients with irritable bowel syndrome refractory to alosetron and tegaserod [abstract]. Gastroenterology. 2005, 128: A329-A330.
8.
Stefanini GF, Prati E, Albini MC, Piccinini G, Capelli S, Castelli E, Mazzetti M, Gasbarrini G: Oral disodium cromoglycate treatment on irritable bowel syndrome: an open study on 101 subjects with diarrheic type. Am J Gastroenterol. 1992, 87: 55-57.PubMed
9.
Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE: The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010, 59: 1213-1221. 10.1136/gut.2010.213108.CrossRefPubMed
10.
Dunlop SP, Jenkins D, Neal KR, Naesdal J, Borgaonker M, Collins SM, Spiller RC: Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2003, 18: 77-84. 10.1046/j.1365-2036.2003.01640.x.CrossRefPubMed
11.
Andrews CN, Petcu R, Griffiths T, Bjarnason J, Chapman K, Cellars L, Vergnolle N, Roux KP: Mesalamine alters colonic mucosal proteolytic activity and fecal bacterial profiles in diarrhea-predominant irritable bowel syndrome (IBS-D). Gastroenterology. 2008, 134: A548-A-
12.
Bafutto M, Almeida JR, Almeida RC, Almeida TC, Leite NV, Filho JR: Treatment of post-infectious irritable bowel syndrome and non infective irritable bowel syndrome with mesalazine [abstract]. Gastroenterology. 2008, 134: A672-
13.
Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, Bartesaghi G, Canovi B, Barbara G: Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther. 2009, 30: 245-252. 10.1111/j.1365-2036.2009.04041.x.CrossRefPubMed
14.
Tuteja A, Hale D, Stoddard G, Fang J, Tolman K: Double-blind placebo controlled study of mesalamine in post-infective irritable bowel syndrome [abstract]. Am J Gastroenterol. 2008, 103: S480-CrossRef
15.
Dunlop SP, Jenkins D, Neal KR, Spiller RC: Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology. 2003, 125: 1651-1659. 10.1053/j.gastro.2003.09.028.CrossRefPubMed
16.
Gwee KA, Leong YL, Graham C, McKendrick MW, Collins SM, Walters SJ, Underwood JE, Read NW: The role of psychological and biological factors in postinfective gut dysfunction. Gut. 1999, 44: 400-406. 10.1136/gut.44.3.400.CrossRefPubMedPubMedCentral
17.
Neal KR, Barker L, Spiller RC: Prognosis in post-infective irritable bowel syndrome: a six year follow up study. Gut. 2002, 51: 410-413. 10.1136/gut.51.3.410.CrossRefPubMedPubMedCentral
18.
Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I: Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002, 122: 1778-1783. 10.1053/gast.2002.33579.CrossRefPubMed
19.
Liebregts T, Adam B, Bredack C, Roth A, Heinzel S, Lester S, Downie-Doyle S, Smith E, Drew P, Talley NJ, Holtmann G: Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007, 132: 913-920. 10.1053/j.gastro.2007.01.046.CrossRefPubMed
20.
Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC: Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol. 2006, 101: 1288-1294. 10.1111/j.1572-0241.2006.00672.x.CrossRefPubMed
21.
Spiller R, Garsed K: Postinfectious irritable bowel syndrome. Gastroenterology. 2009, 136: 1979-1988. 10.1053/j.gastro.2009.02.074.CrossRefPubMed
22.
Fox CC, Moore WC, Lichtenstein LM: Modulation of mediator release from human intestinal mast cells by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1991, 36: 179-184. 10.1007/BF01300753.CrossRefPubMed
23.
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC: Functional bowel disorders. Gastroenterology. 2006, 130: 1480-1491. 10.1053/j.gastro.2005.11.061.CrossRefPubMed
24.
Lackner JM, Gudleski GD, Zack MM, Katz LA, Powell C, Krasner S, Holmes E, Dorscheimer K: Measuring health-related quality of life in patients with irritable bowel syndrome: can less be more?. Psychosom Med. 2006, 68: 312-320. 10.1097/01.psy.0000204897.25745.7c.CrossRefPubMed
25.
Groll D, Vanner SJ, Depew WT, DaCosta LR, Simon JB, Groll A, Roblin N, Paterson WG: The IBS-36: a new quality of life measure for irritable bowel syndrome. Am J Gastroenterol. 2002, 97: 962-971. 10.1111/j.1572-0241.2002.05616.x.CrossRefPubMed
26.
Bracco A, Jonsson B, Ricci JF, Drummond M, Nyhlin H: Economic evaluation of tegaserod vs. placebo in the treatment of patients with irritable bowel syndrome: an analysis of the TENOR study. Value Health. 2007, 10: 238-246. 10.1111/j.1524-4733.2007.00179.x.CrossRefPubMed
27.
Hoad CL, Marciani L, Foley S, Totman JJ, Wright J, Bush D, Cox EF, Campbell E, Spiller RC, Gowland PA: Non-invasive quantification of small bowel water content by MRI: a validation study. Phys Med Biol. 2007, 52: 6909-6922. 10.1088/0031-9155/52/23/009.CrossRefPubMed
28.
Marciani L, Cox EF, Hoad CL, Pritchard S, Totman JJ, Foley S, Mistry A, Evans S, Gowland PA, Spiller RC: Postprandial changes in small bowel water content in healthy subjects and patients with irritable bowel syndrome. Gastroenterology. 2010, 138: 469-477. 10.1053/j.gastro.2009.10.055.CrossRefPubMed
29.
Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S: Enterotypes of the human gut microbiome. Nature. 2011, 473: 174-180. 10.1038/nature09944.CrossRefPubMedPubMedCentral
Metadata
Title
Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): study protocol for a randomised controlled trial
Authors
Matthew P Leighton
Ching Lam
Samir Mehta
Robin C Spiller
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-10

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