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Effect of FODMAPs on Mucosal Inflammation in IBS Patients

20 participantsStarted 2017-11-01

Plain-language summary

OBJECTIVE: To gain mechanistic insights, we will compare effects of low fermentable oligosaccharides, disaccharides and monosaccharides and polyols (FODMAP) and high FODMAP diets on symptoms and colonic protease expression in patients with diarrhea predominant irritable bowel syndrome (IBS-D). We will measure how protease changes affect excitability of pain sensing neurons and correlate this with measurements of the metabolome and the microbiome. DESIGN: We aim to perform a single blind prospective study of patients with diarrhea predominant IBS (Rome IV criteria) who will sequentially consume a high and low FODMAP diets, each for 3 weeks. Symptoms will be assessed using the IBS symptom severity scoring (IBS-SSS). Electrophysiological studies of changes in mouse dorsal root ganglia neurons in response to colonic mucosal/lamina propria supernatants will be carried out. Protease antagonist will be used to specifically assess protease expression. The metabolome will be evaluated using metabolic profiling in urine using mass spectrometry. Stool microbiota composition will be analysed by 16S rRNA gene profiling. All the above testing will be performed at 4 time points: at baseline, 3 weeks following a run-in period, after a 3-week-long high FODMAP diet, and after a 3-week-long low FODMAP diet period. HYPOTHESIS: We anticipate that colonic tissue protease effects on the excitability of dorsal root ganglia (DRG) neurons will increase with a high FODMAP diet and decrease with a low FODMAP diet, but that this may not be found in all patients. The magnitude of the effect may vary and this variation could be due to differences in the individual patients microbiome.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Males and females 18 years of older * Meet the Rome IV criteria for IBS (abdominal pain or discomfort at least 3 days per month in the last three months associated with two or more of the following: defecation, onset associated with change of frequency of stool or change associated with a change in form of stool. The symptoms must be going on for more than six months and be associated with an absence of routine clinical red flags) Exclusion Criteria: * Patients with a history of gastric, small bowel or colonic surgery * Patients with active Inflammatory Bowel Disease * Patients with celiac disease * Patients who are unable or unwilling to come off the following medications: antibiotics, stool bulking agents, narcotics, or lactulose. * Patients who are already on a low-FODMAP diet or a diet that may be have substantially different FODMAP content from usual Canadian diet (paleolithic diet, specific carbohydrate diet, gluten-free diet, Atkins) * Patients cannot have used antibiotics in the past 4 weeks. * Pregnant patients will not be invited to participate. (Sexually active women of child-bearing age will be asked if it is possible that they are pregnant, and if there is a doubt, they will not be invited to participate.) Patients will confirm they are using birth control during the time they are participating in the study.

What they're measuring

Change in Rheobase

Timeframe: Colonic Biopsies will be obtained at baseline, 3 weeks later after a run-in period, 3 weeks after a low FODMAP Diet, and 3 weeks after being on a high FODMAP Diet

Trial details

NCT IDNCT03221790

SponsorQueen's University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2018-07-01

Contact for this trial

Stephen Vanner, MD

613-544-3400 Vanners@hdh.kari.net