Effect of FODMAPs on Mucosal Inflammation in IBS Patients

NCT03221790 | Unknown

• 1 other identifier: 29677
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Irritable Bowel Syndrome With Diarrhea

Keywords

Irritable bowel syndrome; Low FODMAP diet; Mucosal Inflammation

Outcome Measures

Primary Outcomes (1)

• Change in Rheobase

  Number of IBS patients whose supernatants increased neuronal excitability with high FODMAP vs. Low FODMAP diet ( excitability = rheobase = amount of current needed to elicit a single action potential) measured by patch clamp recording of mouse DRG neurons incubated in response to incubation with proteases in the IBS-D supernatants.

  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

Secondary Outcomes (5)

• Questionnaires on IBS symptom severity, stool microbiota, urine and blood metabolome

  This will be done at baseline, after a 3 week run-in period, after a 3 weeks on a high FODMAP Diet, and after 3 weeks on a low FODMAP Diet

• Questionnaire on psychological scores

  This will be done at baseline, after a 3 week run-in period, after a 3 weeks on a low FODMAP Diet, and after 3 weeks on a high FODMAP Diet

• Stool microbiota analysis

  This will be done at baseline, after a 3 week run-in period, after a 3 weeks on a low FODMAP Diet, and after 3 weeks on a high FODMAP Diet

• Urine Metabolome

  This will be done at baseline, after a 3 week run-in period, after a 3 weeks on a high FODMAP Diet, and after 3 weeks on a low FODMAP Diet

• Blood metabolome

  This will be done at baseline, after a 3 week run-in period, after a 3 weeks on a high FODMAP Diet, and after 3 weeks on a low FODMAP Diet

Study Arms (1)

Low and High FODMAP Diets in IBS

EXPERIMENTAL

This study will be comprised of the following four time periods: "baseline", "run-in", "low FODMAP diet", and "high FODMAP diet". Participants will undergo baseline assessment with questionnaires on demographics, IBS symptoms (IBS symptom severity scoring questionnaire), diet, and psychological parameters. Baseline mucosal colonic biopsies will be obtained, and metabolome analysis from urine samples. These will be repeated 3 other times during each of the above time periods. Low FODMAP Diet followed by a High FODMAP Diet

Other: Low FODMAP Diet followed by a High FODMAP Diet

Interventions

Low FODMAP Diet followed by a High FODMAP Diet OTHER

3 weeks on a low FODMAP diet followed by 3 weeks on a high FODMAP Diet

Low and High FODMAP Diets in IBS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Queen's University: lead

Related Publications (2)

• McIntosh K, Reed DE, Schneider T, Dang F, Keshteli AH, De Palma G, Madsen K, Bercik P, Vanner S. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017 Jul;66(7):1241-1251. doi: 10.1136/gutjnl-2015-311339. Epub 2016 Mar 14.

  PMID: 26976734 BACKGROUND

• Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014 Jan;146(1):67-75.e5. doi: 10.1053/j.gastro.2013.09.046. Epub 2013 Sep 25.

  PMID: 24076059 BACKGROUND

MeSH Terms

Conditions

Irritable Bowel Syndrome; Mucositis

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Stephen Vanner, MD

  Queen's University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen Vanner, MD

CONTACT

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

Celine Morissette, PhD

CONTACT

613-544-3400; morissc@hdh.kari.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: July 19, 2017
• Study Start: November 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: February 1, 2019
• Last Updated: October 5, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share