Dietary Triggers of Gastrointestinal Symptoms in IBS Patients

McMaster University34 enrolled

Overview

This crossover randomized controlled trial will evaluate the effects of gluten and gluten combined with amylase-trypsin inhibitors (ATIs) on inducing intestinal and extra-intestinal symptoms in irritable bowel syndrome (IBS) patients. All participants will be put on a gluten-free diet and then challenged with muesli bars containing either purified gluten, gluten with ATIs, or nocebo.

Irritable bowel syndrome (IBS) is a heterogenous, common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. Many IBS patients report symptom relief on a gluten-free diet (GFD), but it is uncertain whether gluten is the true culprit. The gluten-containing grains wheat, rye, and barley all contain amylase-trypsin inhibitors (ATIs), and a GFD is virtually ATI-free. This double-blinded crossover randomized controlled trial aims to determine which IBS patients are affected by pure gluten and which are affected by gluten combined with ATIs. IBS patients who respond to and have been on a GFD for 3+ weeks will be randomized to receive a dietary challenge of muesli bars containing either 1) pure gluten, 2) non-purified gluten (containing ATIs), 3) or nocebo for a week followed by a 14 day washout. This will be repeated until all participants have had each dietary challenge. The study will evaluate the effects and potential mechanisms of purified and non-purified gluten on intestinal and extra-intestinal symptoms in IBS. It is likely that some IBS patients respond to gluten, while others respond to gluten combined with ATIs. Thus, this project may lead to better diagnosis and individualized dietary treatments for IBS.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Irritable Bowel Syndrome

Interventions

Purified glutenOTHER

1 low FODMAPs, vegan muesli bar containing purified gluten per day for 1 week, for a total of 10 g purified gluten per day.

Non-purified gluten (containing ATIs)OTHER

1 low FODMAPs, vegan muesli bar containing whole wheat flour with non-purified gluten per day for 1 week, for a total of 10 g non-purified gluten per day.

NoceboOTHER

1 gluten-free, ATI-free, low FODMAPs, vegan muesli bar per day for 1 week. This is a nocebo because we expect that participants will feel worse even though there is no potential irritant.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * IBS diagnosis based on Rome IV criteria. * Asymptomatic on a gluten-free diet (IBS-SSS score 0-74). * Compliance with the study procedures (according to the investigator's own judgement). * Signing the Study Informed Consent form. Exclusion Criteria: * Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be risky or that could interfere with data collection. * Concurrent organic gastrointestinal disease (i.e. Celiac disease, Inflammatory Bowel Disease, peptic ulcer disease, etc.) other than benign polyps, diverticulosis, hemorrhoids, lipoma and melanosis coli. * Major abdominal surgery with the exception of hernia repair, appendectomy, Caesarian section, tubal ligation, cholecystectomy, hysterectomy, and hemorrhoidectomy. * History of active cancer in the last 5 years, other than skin basal cells cancer. * Pregnant or breastfeeding women. * Current use of antibiotics or antibiotic treatment within 1 months before the first visit. * Consumption of probiotics within 1 month prior to the first visit. * Use of non-authorized medications (see Unauthorized Medications section). * Patients on a high fibre diet (\>35 g/day for males, \> 25 g/day for females), consuming high inulin containing foods (\>5 g/day), and/or consuming dietary fibre supplements (as assessed by dietary assessment questionnaire) in the 4 weeks prior to the first visit. * Patients currently participating or having participated in a trial within the past month.

Locations (1)

McMaster University Medical Centre

Hamilton, Ontario, Canada

RECRUITING

Outcomes

Primary Outcomes

Irritable Bowel Syndrome (IBS) symptoms

Change in IBS symptoms (using Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) during dietary challenge compared to nocebo. The overall score ranges from 0-500 in total, with each of the 5 questions ranging from 0 to 100. A higher score indicates higher symptom severity and the total score is summed.

Time frame: 1 week gluten or gluten+ATIs intervention compared to nocebo

Secondary Outcomes

General gastrointestinal symptoms

Change in general gastrointestinal symptoms (using The Patient-Reported Outcomes Measurement Information System (PROMIS Scales) for belly pain, diarrhea, constipation, or gas \& bloating) during dietary challenge compared to nocebo. Scores are calculated using the Scoring Service by Health Measures and range from 20-80, with medians set at 50 and a standard deviation of 10. Higher scores indicate greater symptom severity. Four PROMIS subscales are being used: Gas \& Bloating, Diarrhea, Constipation, and Belly Pain. Each subscale follows the T-scale scoring range of 20-80 and will be measured independently.

Time frame: 1 week gluten or gluten+ATIs intervention compared to nocebo

Orocecal transit

Change in colonic transit assessed by SHAPE study (radiopaque markers)

Time frame: 1 week gluten or gluten+ATIs intervention compared to nocebo

Anti-gliadin antibody (AGA) levels

Change in AGA levels after gluten and gluten+ATI challenge will be assessed by ELISA

Time frame: Serum AGAs will be measured at baseline and after the challenge

Gut microbiota profiles

Change in gut microbiota profiles will be assessed using 16S rRNA Illumina sequencing

Time frame: 1 week gluten or gluten+ATIs intervention compared to nocebo

Central Contacts

Caroline Seiler, BSc

CONTACT

905-580-0325 seilercl@mcmaster.ca

Data from ClinicalTrials.gov

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