Back to resultsBiomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome
Primary Purpose
Irritable Bowel Syndrome
Status
Recruiting
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
L-Histidine
High-FODMAP beverage
Low-FODMAP beverage
Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.
Placebo
Sponsored by
About this trial
This is an interventional other trial for Irritable Bowel Syndrome focused on measuring FODMAP, microbiota, histamine
Eligibility Criteria
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
Sites / Locations
- McMaster University Medical CentreRecruiting
- Kingston Health Sciences CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group A
Group B
Group C
Arm Description
Participants in group A will undergo challenges in the order: High-FODMAP beverage + placebo probiotic + L-Histidine Low-FODMAP beverage + placebo probiotic + L-Histidine High-FODMAP beverage + probiotic + L-Histidine 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.
Participants in group A will undergo challenges in the order: Low-FODMAP beverage + placebo probiotic + L-Histidine High-FODMAP beverage + probiotic + L-Histidine High-FODMAP beverage + placebo probiotic + L-Histidine. 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.
Participants in group A will undergo challenges in the order: High-FODMAP beverage + probiotic + L-Histidine High-FODMAP beverage + placebo probiotic + L-Histidine Low-FODMAP beverage + placebo probiotic + L-Histidine. 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.
Outcomes
Primary Outcome Measures
Metabolites in stool, urine and blood
Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention.
Secondary Outcome Measures
Expression of hdc gene by stool bacteria
Gram-positive and Gram-negative bacteria will be assessed by PCR using custom designed primers
Stool microbiota composition
16S rRNA Illumina sequencing of stool samples with culture-enriched sequencing.
Worsening of IBS symptoms following High-FODMAP challenge
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.
Changes in IBS symptoms
IBS-SSS continuous data. The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity.
Changes in general GI symptoms
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.
Levels of anxiety, depression and stress
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.
Changes in dietary intake
5-day food diaries will be completed at 5 time points. FODMAP intake will be quantified using Monash University software and database
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04364750
Brief Title
Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome
Official Title
Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2021 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome
Keywords
FODMAP, microbiota, histamine
7. Study Design
Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Participants in group A will undergo challenges in the order:
High-FODMAP beverage + placebo probiotic + L-Histidine
Low-FODMAP beverage + placebo probiotic + L-Histidine
High-FODMAP beverage + probiotic + L-Histidine
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.
Arm Title
Group B
Arm Type
Experimental
Arm Description
Participants in group A will undergo challenges in the order:
Low-FODMAP beverage + placebo probiotic + L-Histidine
High-FODMAP beverage + probiotic + L-Histidine
High-FODMAP beverage + placebo probiotic + L-Histidine.
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.
Arm Title
Group C
Arm Type
Experimental
Arm Description
Participants in group A will undergo challenges in the order:
High-FODMAP beverage + probiotic + L-Histidine
High-FODMAP beverage + placebo probiotic + L-Histidine
Low-FODMAP beverage + placebo probiotic + L-Histidine.
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
L-Histidine
Intervention Description
1 capsule (0.6g) twice daily
Intervention Type
Dietary Supplement
Intervention Name(s)
High-FODMAP beverage
Intervention Description
High-FODMAP beverage (10g of fermentable carbohydrates) consumed twice daily.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low-FODMAP beverage
Intervention Description
Low-FODMAP beverage (10g glucose) consumed twice daily.
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.
Other Intervention Name(s)
Bio-K+ 50 Billion
Intervention Description
Total of 50 billion CFU/capsule taken twice daily.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Enteric coated capsule with no active ingredient, taken twice daily
Primary Outcome Measure Information:
Title
Metabolites in stool, urine and blood
Description
Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention.
Time Frame
six weeks
Secondary Outcome Measure Information:
Title
Expression of hdc gene by stool bacteria
Description
Gram-positive and Gram-negative bacteria will be assessed by PCR using custom designed primers
Time Frame
six weeks
Title
Stool microbiota composition
Description
16S rRNA Illumina sequencing of stool samples with culture-enriched sequencing.
Time Frame
six weeks
Title
Worsening of IBS symptoms following High-FODMAP challenge
Description
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.
Time Frame
six weeks
Title
Changes in IBS symptoms
Description
IBS-SSS continuous data. The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity.
Time Frame
six weeks
Title
Changes in general GI symptoms
Description
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.
Time Frame
six weeks
Title
Levels of anxiety, depression and stress
Description
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.
Time Frame
six weeks
Title
Changes in dietary intake
Description
5-day food diaries will be completed at 5 time points. FODMAP intake will be quantified using Monash University software and database
Time Frame
six weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Seiler, BSc
Phone
9055212100
Ext
21922
Email
seilercl@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Nardelli, PhD
Phone
9055212100
Ext
21922
Email
nardela@mcmaster.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Premysl Bercik, MD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen Vanner, MD
Organizational Affiliation
Queens University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster University Medical Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Seiler, BSc
Phone
9055212100
Ext
21922
Email
seilercl@mcmaster.ca
First Name & Middle Initial & Last Name & Degree
Andrea Nardelli, PhD
Phone
9055212100
Ext
21922
Email
nardela@mcmaster.ca
First Name & Middle Initial & Last Name & Degree
Premysl Bercik, MD
Facility Name
Kingston Health Sciences Centre
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celine Morissette
Phone
(613) 544-3400
Ext
2479
Email
celine.morissette@kingstonhsc.ca
First Name & Middle Initial & Last Name & Degree
Stephen Vanner, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome
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