Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome(IBS-D)
Lead Research Organisation:
University of Nottingham
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Scientific Abstract|RESEARCH DESIGN: A randomised, placebo-controlled, parallel group design evaluating the effect of Mesalazine on IBS symptoms, mast cell numbers and secretion, and small bowel tone in IBS-D patients. STUDY POPULATION: 108 IBS-D patients aged 18-75 years meeting Rome III criteria. |PLANNED INTERVENTION: 12 weeks Mesalazine 800 mgs tds compared with placebo. Patients will complete a daily symptom diary for two weeks prior to randomisation and then during the 12 weeks of treatment. At randomisation and at 12 weeks, they will undergo 1) flexible sigmoidoscopy and biopsy to allow quantification of numbers of mucosal inflammatory and mast cells per high powered field. Biopsies will also be incubated and release of inflammatory mediators measured 2) MRI scanning both fasting and for 4 hours postprandially to assess small bowel water content and indirectly intestinal tone. Patients will also complete validated anxiety, depression and somatisation questionnaires at entry. |PRIMARY OUTCOME MEASURES: |CLINICAL: Reduction in stool frequency, averaged over weeks 11 and 12 compared with average of 2 weeks prior to randomisation. |MECHANISTIC: Reduction in mucosal mast cell counts |SECONDARY OUTCOME MEASURES: |CLINICAL: 1.Decrease in IBS symptom severity score, 2.% patients achieving satisfactory relief of IBS symptoms MECHANISTIC: 1.Change in mast cell tryptase release from mucosal biopsy 2.Reduction in stool mast cell tryptase concentrations 3.Change in small bowel tone a) fasting b) average 0-4 hrs post prandially |ASSESSEMENT AND FOLLOW-UP: Since Mesalazine is expected to have 1-2 months to have its full effect the assessment will be by means of daily stool diary analysed in the last 2 weeks. Visits are planned at 2, 4, 8 and 12 weeks for safety monitoring. |PROPOSED SAMPLE SIZE: 96 patients based on the primary end point of stool frequency. Our previous study on IBS-D patients gives a mean stool frequency of 3.1 (SD 2.0). Tuteja et al 2008 reported Mesalazine decreasing stool frequency by 1.4 bowel movements per day. Our study will have an 80% power to detect such an effect at the 1% significance level (90% at 5% significance). Allowing for a 10% dropout we will recruit 108. |STATISTICAL ANALYSIS: Analysis of the Primary outcome measure will be performed using an Analysis of Covariance in the form of a General Linear Model incorporating terms for baseline frequency, treatment arm, centre, age, diet and gender. All analyses will be performed using the current version of Stata. PROJECT TIME TABLE 0-6 Months: Set up and regulatory approval. 6-24 Months: Recruitment: 70 in Nottingham and 40 in Manchester. We have recruited 25 IBS patients in the first 6 months of this year and see 450 new IBS patients /year with 700 IBS-D/ year at the Manchester centre. 27 Months: Last patient out, lock database and undertake final analysis 27 - 33 Months: Complete analysis 33 - 36 Months: Write up and publish. |
People |
ORCID iD |
Robin Spiller (Principal Investigator) |
Publications
Spiller R
(2011)
The shifting interface between IBS and IBD.
in Current opinion in pharmacology
Spiller R
(2012)
An Update on Post-infectious Irritable Bowel Syndrome: Role of Genetics, Immune Activation, Serotonin and Altered Microbiome.
in Journal of neurogastroenterology and motility
Murray KA
(2016)
Corticotropin-releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomized controlled trial.
in The American journal of clinical nutrition
Lam C
(2017)
Distinct Abnormalities of Small Bowel and Regional Colonic Volumes in Subtypes of Irritable Bowel Syndrome Revealed by MRI.
in The American journal of gastroenterology
Lam C
(2019)
Increased fasting small-bowel water content in untreated coeliac disease and scleroderma as assessed by magnetic resonance imaging.
in United European gastroenterology journal
Gunn D
(2019)
Abnormalities of mucosal serotonin metabolism and 5-HT3 receptor subunit 3C polymorphism in irritable bowel syndrome with diarrhoea predict responsiveness to ondansetron.
in Alimentary pharmacology & therapeutics
Cibert-Goton V
(2021)
Pain Severity Correlates With Biopsy-Mediated Colonic Afferent Activation But Not Psychological Scores in Patients With IBS-D.
in Clinical and translational gastroenterology
Jalanka J
(2021)
Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine.
in Journal of neurogastroenterology and motility
Eijsbouts C
(2021)
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
in Nature genetics
Description | Afferent nerve responses to IBS biopsy supernatant |
Organisation | Queen Mary University of London |
Department | Clinical Research Facilities |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | collecting biopsy supernatants from IBS patients as part of trial |
Collaborator Contribution | Study of afferent response to biopsy supernatants from IBS patients |
Impact | Response to human afferent nerves to supernatants from IBS patient correlate with severity of abdominal pain |
Start Year | 2014 |