Dietary Triggers of Gastrointestinal Symptoms in IBS Patients

Irritable Bowel Syndrome Clinical Trial

Official title:

Crossover Trial of Gluten and Gluten With Amylase-trypsin Inhibitors as Triggers of Gastrointestinal Symptoms in Patients With Irritable Bowel Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03664531
• Other study ID #: Diet in IBS
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2019
• Est. completion date: February 2022

Study information

• Verified date: September 2020
• Source: McMaster University
• Contact: Caroline Seiler, BSc
• Phone: 905-580-0325
• Email: seilercl[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: February 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Irritable Bowel Syndrome
• Syndrome

Intervention

Other:
• Purified gluten
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)
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.
• Nocebo
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.

Locations

Country	Name	City	State
Canada	McMaster University Medical Centre	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (62)

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* Note: There are 62 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	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.	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Orocecal transit	Change in colonic transit assessed by SHAPE study (radiopaque markers)	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Anti-gliadin antibody (AGA) levels	Change in AGA levels after gluten and gluten+ATI challenge will be assessed by ELISA	Serum AGAs will be measured at baseline and after the challenge
Secondary	Gut microbiota profiles	Change in gut microbiota profiles will be assessed using 16S rRNA Illumina sequencing	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Genetic predisposition for celiac disease	Patient HLADQ2/8 status will be assessed at baseline	Patient HLA DQ2/8 status will be measured at baseline
Secondary	Depression, anxiety and stress	Change in depression, anxiety, and stress sub-scales during dietary challenge will be assessed by Depression Anxiety Stress Scale (DASS-21). The DASS-21 has 21 questions. The three subscales (depression, anxiety, and stress) will be reported independently and range from 0 to 42, with higher scores indicating greater symptom severity.	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Somatic symptoms	Change in somatic symptoms like fatigue, sleeping trouble, and pain will be assessed using Patient Health Questionnaire (PHQ-15). Scores range from 0 to 30, with greater scores indicating greater severity.	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Stool consistency	Changes in stool consistency will be assessed by Bristol Stool Scale. Types 1 and 2 indicate harder stools, types 3, 4, and 5 are normal, and types 6 and 7 indicate runnier, more liquid stool.	1 week gluten or gluten+ATIs intervention compared to nocebo
Secondary	Gluten levels in stool	Presence of gluten in stool samples will be tested for diet compliance using Anti-GIP immunochromatographic strips	Procedure will be explained at baseline
Secondary	Diet assessment	Dietary tracking will be performed using the MealLogger app	Patients will be asked to take pictures of all meals during each of the 1 week diet challenges
Secondary	IBS symptom duration	Evaluates symptom duration at the end of the diet challenge using the IBS-SSS. 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.	Completed daily for 7 days after each diet challenge
Secondary	Systemic immune reactivity	Assessment of pro-inflammatory cytokines levels using peripheral blood mononuclear cell stimulation (PBMC) stimulation in a subset of patients	1 week gluten or gluten+ATIs intervention compared to nocebo