Dietary Triggers of Gastrointestinal Symptoms in IBS Patients

NCT03664531 | Completed Results

• 1 other identifier: Diet in IBS
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This crossover randomized controlled trial will evaluate the effects of purified gluten and whole wheat (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, whole wheat (gluten with ATIs), or gluten-free sham.

Conditions

Irritable Bowel Syndrome

Keywords

crossover; gluten; amylase trypsin inhibitors; diet; challenge

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Worsening Irritable Bowel Syndrome (IBS) Symptoms Based on IBS-SSS

  Number of participants with a clinically meaningful worsening of symptoms during dietary challenge compared to sham, as defined by an increase of \>50 points in the Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS). The IBS-SSS ranges from 0 to 500, with higher scores indicating greater symptom severity. A \>50-point increase is considered a clinically significant worsening.

  1 week purified gluten or whole wheat (gluten+ATIs) intervention versus gluten-free sham. Outcomes were measured at baseline for Pre-Sham, Pre-Gluten and Pre-Wheat Arm/Groups and 1 week for Sham, Gluten and Wheat Arm/Groups.

Secondary Outcomes (15)

• General Gastrointestinal Symptoms

  1 week purified gluten or whole wheat (gluten+ATIs) intervention compared to gluten-free sham. Outcomes were measured at 1 week for Sham, Gluten and Wheat Arm/Groups.

• Orocecal Transit

  Assessed at 1 week after each intervention period (Sham, Gluten, and Wheat).

• Anti-gliadin Antibody (AGA) Levels

  Serum AGAs were measured at baseline.

• Gut Microbiota Profiles

  Stool samples collected at 1 week after each intervention period (Sham, Gluten, and Wheat)

• Genetic Predisposition for Celiac Disease

  Patient HLA DQ2/8 status were measured at baseline

Study Arms (6)

Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham

EXPERIMENTAL

Participants will start on 1 week of muesli bars with 10 g purified gluten followed by 14 days washout. They will then take 1 week of muesli bars with whole wheat (containing 10 g non-purified gluten and wheat ATIs) followed by 14 days of washout. Finally, they will have 1 week of gluten-free sham muesli bars (with nothing).

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Purified Gluten (10 g), Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs)

EXPERIMENTAL

Participants will start on 1 week of muesli bars with 10 g purified gluten followed by 14 days washout. They will then take 1 week of gluten-free sham muesli bars (with nothing) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with whole wheat (containing 10 g non-purified gluten and wheat ATIs).

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g), Gluten-free Sham

EXPERIMENTAL

Participants will start on 1 week of muesli bars with whole wheat (containing 10 g non-purified gluten and wheat ATIs) followed by 14 days washout. They will then take 1 week of muesli bars with 10 g purified gluten followed by 14 days of washout. Finally, they will have 1 week of gluten-free sham muesli bars (with nothing).

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham, Purified Gluten (10 g)

EXPERIMENTAL

Participants will start on 1 week of muesli bars with whole wheat (containing 10 g non-purified gluten and wheat ATIs) followed by 14 days washout. They will then take 1 week of gluten-free sham muesli bars (containing nothing) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with 10 g purified gluten.

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g)

EXPERIMENTAL

Participants will start on 1 week of gluten-free sham muesli bars (with nothing) followed by 14 days washout. They will then take 1 week of muesli bars containing whole wheat (containing 10 g non-purified gluten and wheat ATIs) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with 10 g purified gluten.

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Gluten-free Sham, Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs)

EXPERIMENTAL

Participants will start on 1 week of gluten-free sham muesli bars (with nothing) followed by 14 days washout. They will then take 1 week of muesli bars with 10 g purified gluten followed by 14 days of washout. Finally, they will have 1 week of muesli bars with whole wheat (containing 10 g non-purified gluten and wheat ATIs).

Other: Purified gluten; Other: Non-purified gluten (containing ATIs); Other: Sham

Interventions

Purified gluten OTHER

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

Gluten-free Sham, Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs); Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g); Purified Gluten (10 g), Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs); Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham; Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham, Purified Gluten (10 g); Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g), Gluten-free Sham

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.

Gluten-free Sham, Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs); Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g); Purified Gluten (10 g), Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs); Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham; Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham, Purified Gluten (10 g); Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g), Gluten-free Sham

Sham OTHER

1 gluten-free, ATI-free, low FODMAPs, vegan muesli bar per day for 1 week. This is a sham because participants were blinded to the identity of this gluten-free control and randomly assigned to it.

Gluten-free Sham, Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs); Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g); Purified Gluten (10 g), Gluten-free Sham, Whole Wheat (containing 10 g Gluten and Wheat ATIs); Purified Gluten (10 g), Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham; Whole Wheat (containing 10 g Gluten and Wheat ATIs), Gluten-free Sham, Purified Gluten (10 g); Whole Wheat (containing 10 g Gluten and Wheat ATIs), Purified Gluten (10 g), Gluten-free Sham

Eligibility Criteria

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

You may qualify if:

• IBS diagnosis based on Rome IV criteria.
• Previously improved while on a gluten-free diet.
• Compliance with the study procedures (according to the investigator's own judgement).
• Signing the Study Informed Consent form.

You may not qualify if:

• 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.

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

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• Evans RC, Kamm MA, Hinton JM, Lennard-Jones JE. The normal range and a simple diagram for recording whole gut transit time. Int J Colorectal Dis. 1992 Feb;7(1):15-7. doi: 10.1007/BF01647654.

  PMID: 1588218 RESULT

• Seiler CL, Rueda GH, Miranda PM, Nardelli A, Borojevic R, Hann A, Rahmani S, De Souza R, Caminero A, Curella V, Neerukonda M, Vanner S, Schuppan D, Moayyedi P, Collins SM, Verdu EF, Pinto-Sanchez MI, Bercik P. Effect of gluten and wheat on symptoms and behaviours in adults with irritable bowel syndrome: a single-centre, randomised, double-blind, sham-controlled crossover trial. Lancet Gastroenterol Hepatol. 2025 Sep;10(9):794-805. doi: 10.1016/S2468-1253(25)00090-1. Epub 2025 Jul 21.

  PMID: 40706614 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Dr. Premysl Bercik
• Organization: McMaster University

bercikp@mcmaster.ca

905-525-9140

Study Officials

• Premysl Bercik, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Maria Ines Pinto-Sanchez, MD

  McMaster University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The statistician will also be masked from the treatments.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor

Model Details: Participants will be required to be on a gluten-free diet for a period of 3 weeks before starting the study. Participants will then be randomized to take muesli bars containing either 10 g purified gluten, whole wheat (containing 10 g non-purified gluten with wheat amylase trypsin inhibitors), or gluten-free sham for 1 week followed by 2 weeks of washout, and then repeated for the two remaining dietary challenges so that at the end all participants have been on all dietary challenges. At the beginning and end of each challenge period, participants will visit the clinic to be evaluated for changes in IBS symptoms.

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: September 10, 2018
• Study Start: January 1, 2019
• Primary Completion: April 1, 2022
• Study Completion: June 20, 2023
• Last Updated: April 1, 2026
• Results First Posted: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)