Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome
Most patients suffering from the irritable bowel syndrome (IBS) report that ingestion of certain foods is a major trigger of symptoms, but the reason is unclear. Previous studies have shown that foods containing poorly absorbed carbohydrates (FODMAPs) are fermented by the bacteria in our bowels and these cause symptoms in some but not all patients. Gut bacteria are capable of producing various products, such as neuroimmune mediator histamine, that may be related to IBS symptoms. Our recent data suggest that consumption of FODMAPs promotes production of bacterial histamine.
The main objective of this study is to investigate bacterial production of histamine and its relationship to IBS symptoms. The study will involve 6 weeks on a low-FODMAP diet with three three-day interventions consisting of High- or Low-FODMAP drinks along with probiotics or placebo capsules. The patient's bacteria and metabolites will be analyzed at various time points.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- McMaster University Medical Centre
-
Kingston, Ontario, Canada, K7L 2V7
- Kingston Health Sciences Centre
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adults aged 18-75 with IBS (Rome IV criteria) who have self-reported previous improvement in their IBS symptoms while on a low FODMAP diet, or when excluding certain high-FODMAP foods, or patients in whom histamine is expected to play a key role (either diagnosed with high histamine producing bacteria, or improved IBS symptoms after using antihistamines). Individuals should be able to swallow size 00 capsules.
Exclusion Criteria:
- Concurrent significant organic GI pathology (i.e. celiac, IBD, etc.)
- Concurrent systemic disease (such as diabetes) and/or laboratory abnormalities considered by investigators to be risky or that could interfere with data collection
- History of active cancer in the last 5 years, other than basal cell cancer
- Pregnant or breastfeeding women
- Active or recent participation (< 1 month) in a clinical study, except for SPOR IMAGINE
- Use of antibiotics, probiotics, or ACE inhibitors during, or one month prior to the study
- Use of new medications less than 4 weeks prior to the study.
- Allergies to any of the ingredients used in the study
- Any immune-compromising conditions
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Group A
Participants in group A will undergo challenges in the order:
Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges. |
1 capsule (0.6g) twice daily
High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.
Low-FODMAP beverage (10g glucose) consumed twice daily.
Total of 50 billion CFU/capsule taken twice daily.
Other Names:
Enteric coated capsule with no active ingredient, taken twice daily
|
|
Experimental: Group B
Participants in group A will undergo challenges in the order:
Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges. |
1 capsule (0.6g) twice daily
High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.
Low-FODMAP beverage (10g glucose) consumed twice daily.
Total of 50 billion CFU/capsule taken twice daily.
Other Names:
Enteric coated capsule with no active ingredient, taken twice daily
|
|
Experimental: Group C
Participants in group A will undergo challenges in the order:
Challenges each last 5 days, but the FODMAP drinks and the L-Histidine capsules are only taken for the last three days. There is a 10 day washout period between challenges. |
1 capsule (0.6g) twice daily
High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.
Low-FODMAP beverage (10g glucose) consumed twice daily.
Total of 50 billion CFU/capsule taken twice daily.
Other Names:
Enteric coated capsule with no active ingredient, taken twice daily
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Metabolites in stool, urine and blood
Time Frame: six weeks
|
Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention.
|
six weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Expression of hdc gene by stool bacteria
Time Frame: six weeks
|
Gram-positive and Gram-negative bacteria will be assessed by PCR using custom designed primers
|
six weeks
|
|
Stool microbiota composition
Time Frame: six weeks
|
16S rRNA Illumina sequencing of stool samples with culture-enriched sequencing.
|
six weeks
|
|
Worsening of IBS symptoms following High-FODMAP challenge
Time Frame: six weeks
|
Increase by ≥50 points on IBS Symptom Severity Score (IBS-SSS).
The score will be used as a dichotomous variable.
The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity.
|
six weeks
|
|
Changes in IBS symptoms
Time Frame: six weeks
|
IBS-SSS continuous data.
The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity.
|
six weeks
|
|
Changes in general GI symptoms
Time Frame: six weeks
|
Patient-Reported Outcomes Measurement Information System (PROMIS) for general GI symptoms.
Four subscales will be used: Gas & Bloating, Diarrhea, Constipation, and Belly Pain.
T-scores are calculated using the Scoring Service by Health Measures and range from 34.7 - 79.0 (Gas & Bloating), 39.9 - 75.2 (Diarrhea), 40.6 - 80.8 (Constipation), and 33.9 - 80.0 (Belly Pain).
On this scale, 50 indicates the mean of the general population and a difference of 10 is a standard deviation.
Higher scores indicate greater symptom severity.
|
six weeks
|
|
Levels of anxiety, depression and stress
Time Frame: six weeks
|
Depression Anxiety Stress Scale (DASS-21) to assess psychiatric comorbidity and stress.
The scale scores range from 0 - 42 with higher scores indicating worse outcomes.
|
six weeks
|
|
Changes in dietary intake
Time Frame: six weeks
|
5-day food diaries will be completed at 5 time points.
FODMAP intake will be quantified using Monash University software and database
|
six weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stephen Vanner, MD, Queens University
- Principal Investigator: Premysl Bercik, MD, McMaster University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BFIBS
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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