Biomarkers of Diet-microbiota Interactions in Irritable Bowel Syndrome

Early Phase 1

Recruiting

• Conditions: Irritable Bowel Syndrome
• Interventions: Dietary Supplement: L-Histidine; Dietary Supplement: High-FODMAP beverage; Dietary Supplement: Low-FODMAP beverage; Dietary Supplement: Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.; Other: Placebo

• Registration Number: NCT04364750
• Lead Sponsor: McMaster University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-23
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-28
• Study Start: 2021-07-15
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-25
• Last Update Posted: 2023-09-26
• Primary Completion: 2024-02
• Study Completion: 2024-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group B	Low-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. 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.
Group B	Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.	Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. 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.
Group B	Placebo	Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. 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.
Group C	L-Histidine	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group A	Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group B	L-Histidine	Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. 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.
Group A	L-Histidine	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group A	High-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group A	Low-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group A	Placebo	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + placebo probiotic + L-Histidine 2. Low-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group C	High-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group B	High-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. Low-FODMAP beverage + placebo probiotic + L-Histidine 2. High-FODMAP beverage + probiotic + L-Histidine 3. 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.
Group C	Low-FODMAP beverage	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group C	Lactobacillus acidophilus CL1285, L. casei LBC80R and L. rhamnosus CLR2.	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.
Group C	Placebo	Participants in group A will undergo challenges in the order: 1. High-FODMAP beverage + probiotic + L-Histidine 2. High-FODMAP beverage + placebo probiotic + L-Histidine 3. 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.

Primary Outcome Measures

Name	Time	Method
Metabolites in stool, urine and blood	six weeks	Metabolites will be measured by LC-MS and ELISA at baseline and before and after each intervention.

Secondary Outcome Measures

Name	Time	Method
Changes in IBS symptoms	six weeks	IBS-SSS continuous data. The overall score ranges from 0 to 500, with higher scores indicating greater symptom severity.
Levels of anxiety, depression and stress	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.
Expression of hdc gene by stool bacteria	six weeks	Gram-positive and Gram-negative bacteria will be assessed by PCR using custom designed primers
Changes in dietary intake	six weeks	5-day food diaries will be completed at 5 time points. FODMAP intake will be quantified using Monash University software and database
Stool microbiota composition	six weeks	16S rRNA Illumina sequencing of stool samples with culture-enriched sequencing.
Worsening of IBS symptoms following High-FODMAP challenge	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.
Changes in general GI symptoms	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.

Trial Locations

Locations (2)

McMaster University Medical Centre; 🇨🇦 Hamilton, Ontario, Canada

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada