Dietary Triggers of Gastrointestinal Symptoms in IBS Patients
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Gluten, ATIs, nocebo Participants will start on 1 week of muesli bars with purified gluten followed by 14 days washout. They will then take 1 week of muesli bars with non-purified gluten (containing ATIs) followed by 14 days of washout. Finally, they will have 1 week of nocebo muesli bars (with nothing). |
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.
Other: 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.
Other: 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.
|
Experimental: Gluten, nocebo, ATIs Participants will start on 1 week of muesli bars with purified gluten followed by 14 days washout. They will then take 1 week of nocebo muesli bars (with nothing) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with non-purified gluten (containing ATIs). |
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.
Other: 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.
Other: 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.
|
Experimental: ATIs, gluten, nocebo Participants will start on 1 week of muesli bars with non-purified gluten (containing ATIs) followed by 14 days washout. They will then take 1 week of muesli bars with purified gluten followed by 14 days of washout. Finally, they will have 1 week of nocebo muesli bars (with nothing). |
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.
Other: 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.
Other: 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.
|
Experimental: ATIs, nocebo, gluten Participants will start on 1 week of muesli bars with non-purified gluten (containing ATIs) followed by 14 days washout. They will then take 1 week of nocebo muesli bars (containing nothing) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with purified gluten. |
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.
Other: 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.
Other: 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.
|
Experimental: Nocebo, ATIs, gluten Participants will start on 1 week of nocebo muesli bars (with nothing) followed by 14 days washout. They will then take 1 week of muesli bars containing non-purified gluten (containing ATIs) followed by 14 days of washout. Finally, they will have 1 week of muesli bars with purified gluten. |
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.
Other: 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.
Other: 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.
|
Experimental: Nocebo, gluten, ATIs Participants will start on 1 week of nocebo muesli bars (with nothing) followed by 14 days washout. They will then take 1 week of muesli bars with purified gluten followed by 14 days of washout. Finally, they will have 1 week of muesli bars with non-purified gluten (containing ATIs). |
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.
Other: 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.
Other: 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.
|
Outcome Measures
Primary Outcome Measures
- Irritable Bowel Syndrome (IBS) symptoms [1 week gluten or gluten+ATIs intervention compared to nocebo]
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.
Secondary Outcome Measures
- General gastrointestinal symptoms [1 week gluten or gluten+ATIs intervention compared to nocebo]
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.
- Orocecal transit [1 week gluten or gluten+ATIs intervention compared to nocebo]
Change in colonic transit assessed by SHAPE study (radiopaque markers)
- Anti-gliadin antibody (AGA) levels [Serum AGAs will be measured at baseline and after the challenge]
Change in AGA levels after gluten and gluten+ATI challenge will be assessed by ELISA
- Gut microbiota profiles [1 week gluten or gluten+ATIs intervention compared to nocebo]
Change in gut microbiota profiles will be assessed using 16S rRNA Illumina sequencing
- Genetic predisposition for celiac disease [Patient HLA DQ2/8 status will be measured at baseline]
Patient HLADQ2/8 status will be assessed at baseline
- Depression, anxiety and stress [1 week gluten or gluten+ATIs intervention compared to nocebo]
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.
- Somatic symptoms [1 week gluten or gluten+ATIs intervention compared to nocebo]
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.
- Stool consistency [1 week gluten or gluten+ATIs intervention compared to nocebo]
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.
- Gluten levels in stool [Procedure will be explained at baseline]
Presence of gluten in stool samples will be tested for diet compliance using Anti-GIP immunochromatographic strips
- Diet assessment [Patients will be asked to take pictures of all meals during each of the 1 week diet challenges]
Dietary tracking will be performed using the MealLogger app
- IBS symptom duration [Completed daily for 7 days after each diet challenge]
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.
- Systemic immune reactivity [1 week gluten or gluten+ATIs intervention compared to nocebo]
Assessment of pro-inflammatory cytokines levels using peripheral blood mononuclear cell stimulation (PBMC) stimulation in a subset of patients
Eligibility Criteria
Criteria
Inclusion Criteria:
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IBS diagnosis based on Rome IV criteria.
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Asymptomatic on a gluten-free diet (IBS-SSS score 0-74).
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Compliance with the study procedures (according to the investigator's own judgement).
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Signing the Study Informed Consent form.
Exclusion Criteria:
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Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be risky or that could interfere with data collection.
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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.
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Major abdominal surgery with the exception of hernia repair, appendectomy, Caesarian section, tubal ligation, cholecystectomy, hysterectomy, and hemorrhoidectomy.
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History of active cancer in the last 5 years, other than skin basal cells cancer.
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Pregnant or breastfeeding women.
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Current use of antibiotics or antibiotic treatment within 1 months before the first visit.
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Consumption of probiotics within 1 month prior to the first visit.
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Use of non-authorized medications (see Unauthorized Medications section).
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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.
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Patients currently participating or having participated in a trial within the past month.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | McMaster University Medical Centre | Hamilton | Ontario | Canada | L8N 3Z5 |
Sponsors and Collaborators
- McMaster University
Investigators
- Principal Investigator: Premysl Bercik, MD, McMaster University
- Study Director: Maria Ines Pinto-Sanchez, MD, McMaster University
Study Documents (Full-Text)
None provided.More Information
Publications
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- Diet in IBS