Identification of IBS Metabotypes Based on Physiological Responses to Food

NCT03653689 | Completed

• 1 other identifier: OpDiMet1
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, constipation, diarrhea and gas and affects up to 15% of the Western population. In many individuals with IBS, symptoms can be triggered by foods, such as FODMAPs (easily fermentable dietary fiber containing Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols). Some individuals with IBS may also benefit from a gluten-free diet. Current subtypes of IBS are based on symptoms (constipation, diarrhea, and mixed), rather than mechanistic differences. Another promising approach for identifying IBS subtypes is based on grouping individuals into similar metabolic phenotypes, i.e. metabotypes, that share similarities in metabolism and metabolic regulation in response to specific foods. Health and wellbeing could potentially be improved by personalized treatment through tailoring diet to subjects with different IBS subtypes. To investigate this hypothesis, the investigators will conduct an intervention study on subjects with IBS and identify specific food susceptibilities based on metabolic phenotype (metabotype). In total, 120 women and men with moderate to severe IBS will be recruited. Gluten intolerance, other gastrointestinal disease and abdominal surgery will constitute exclusion criteria. The study will be performed in a double-blind, randomized, placebo-controlled cross-over study design. Study participants will receive three 1-week diets with additions of either FODMAPs, gluten or an inert control with 1-week washout in-between. IBS metabotypes will be identified by integrative multivariate analysis of molecular phenotype data from metabolomics and microbiota measurements combined with data on bowel habits and stomach discomfort. Study participants will also be subjected to a cocktail provocation containing FODMAPs and gluten to develop a rapid diagnostic test based on identified plasma metabolomic biomarkers of IBS metabotypes.

Conditions

Irritable Bowel Syndrome

Keywords

IBS; metabotype; FODMAP; gluten

Outcome Measures

Primary Outcomes (1)

• IBS-SSS

  The questionnaire IBS-SSS will be used to monitor the IBS symptoms and relate it to how participants metabolically react to the diets (gluten, FODMAPS and control). The IBS-SSS will also be related to how the microbiota potentially could differentiate between individuals and how it can be related to the diets (gluten, FODMAPS and control).

  When the study is completed, anticipated in 1-2 year

Secondary Outcomes (3)

• BMI

  When the study is completed, anticipated in 1-2 year

• Blood pressure

  When the study is completed, anticipated in 1-2 year

• Heart rate

  When the study is completed, anticipated in 1-2 year

Study Arms (3)

FODMAPs

ACTIVE COMPARATOR

Dietary supplement: FODMAPs 50 grams three servings per day for seven days.

Dietary Supplement: FODMAP; Dietary Supplement: Gluten; Dietary Supplement: Placebo

Gluten

ACTIVE COMPARATOR

Dietary supplement: Gluten 17.3 grams three servings per day for seven days.

Dietary Supplement: FODMAP; Dietary Supplement: Gluten; Dietary Supplement: Placebo

Placebo

PLACEBO COMPARATOR

Dietary supplement: Placebo rice porrige three servings per day for seven days.

Dietary Supplement: FODMAP; Dietary Supplement: Gluten; Dietary Supplement: Placebo

Interventions

FODMAP DIETARY_SUPPLEMENT

The intervention will run for seven weeks. During the whole intervention, the participants will hold a baseline diet with no gluten and low intake of FODMAPs. The first week, the participants will consume a one-time cocktail provocation consisting of gluten (17.3 gram) and FODMAPs (50 gram) Thereafter, study participants will receive three 1-week diets with additions of either FODMAPs, gluten or an inert control with 1-week washout in-between. The daily amount for gluten will be 17.3 gram and the daily amount for FODMAPs will be 50 gram. The order of the three weeks with extra diets (gluten/FODMAPs/control) will be randomized.

FODMAPs; Gluten; Placebo

Gluten DIETARY_SUPPLEMENT

The intervention will run for seven weeks. During the whole intervention, the participants will hold a baseline diet with no gluten and low intake of FODMAPs. The first week, the participants will consume a one-time cocktail provocation consisting of gluten (17.3 gram) and FODMAPs (50 gram) Thereafter, study participants will receive three 1-week diets with additions of either FODMAPs, gluten or an inert control with 1-week washout in-between. The daily amount for gluten will be 17.3 gram and the daily amount for FODMAPs will be 50 gram. The order of the three weeks with extra diets (gluten/FODMAPs/control) will be randomized.

FODMAPs; Gluten; Placebo

Placebo DIETARY_SUPPLEMENT

The intervention will run for seven weeks. During the whole intervention, the participants will hold a baseline diet with no gluten and low intake of FODMAPs. The first week, the participants will consume a one-time cocktail provocation consisting of gluten (17.3 gram) and FODMAPs (50 gram) Thereafter, study participants will receive three 1-week diets with additions of either FODMAPs, gluten or an inert control with 1-week washout in-between. The daily amount for gluten will be 17.3 gram and the daily amount for FODMAPs will be 50 gram. The order of the three weeks with extra diets (gluten/FODMAPs/control) will be randomized.

FODMAPs; Gluten; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Men and women
• Medium to severe IBS
• Age 18-70 years
• BMI 18.5-38 kg/m2
• Hb 120-160 g/L
• S-TSH \<4 mIU/L
• S-CRP \<5 mg/L
• S-Transglutaminase IgA \<7 U/mL
• Willingness to consume rice porridge, once a day for 3 weeks
• Any medication stable for the last 14 days.

You may not qualify if:

• Gluten intolerance
• Other gastrointestinal disease (e.g. Crohn's disease, ulcerative colitis)
• Performed bariatric surgery
• Previous abdominal surgery, other than appendectomy.
• Food adaptation (eg. vegetarian, LCHF) in order to achieve abdominal relief
• Medical treatment for weight reduction.
• ≥10 kg of weight change in the last 12 months
• Diastolic blood pressure more than 105 mm Hg at visit 1
• Systolic blood pressure more than 160 mm at visit 1
• Blood donation or participation in a clinical study with blood sampling within 30 days prior to screening visit and throughout the study
• Pregnant or lactating or wishes to become pregnant during the period of the study.
• Pharmacological medication with drugs known to possibly affect gastrointestinal function, eg antidepressants, neuroleptics, proton pump inhibitors, H2-receptor blockers, non-steroidal anti-inflammatory drugs, opioids, loperamide, cholestyramine, laxatives, metoclopramide, domperidone, prucalopride, linaclotide
• Unstable pharmacological medication
• History of drug or alcohol abuse
• Using nicotine products on a daily basis (incl. chewing gum, patches, snus etc.)

Sponsors & Collaborators

• Uppsala University: lead
• Chalmers University of Technology: collaborator

Study Sites (1)

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (6)

• Shankar V, Reo NV, Paliy O. Simultaneous fecal microbial and metabolite profiling enables accurate classification of pediatric irritable bowel syndrome. Microbiome. 2015 Dec 9;3:73. doi: 10.1186/s40168-015-0139-9.

  PMID: 26653757 RESULT

• McIntosh K, Reed DE, Schneider T, Dang F, Keshteli AH, De Palma G, Madsen K, Bercik P, Vanner S. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017 Jul;66(7):1241-1251. doi: 10.1136/gutjnl-2015-311339. Epub 2016 Mar 14.

  PMID: 26976734 RESULT

• Nordin E, Landberg R, Hellstrom PM, Brunius C. Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study. Metabolomics. 2024 Feb 12;20(2):21. doi: 10.1007/s11306-023-02083-x.

  PMID: 38347192 DERIVED

• Nordin E, Hellstrom PM, Vuong E, Ribbenstedt A, Brunius C, Landberg R. IBS randomized study: FODMAPs alter bile acids, phenolic- and tryptophan metabolites, while gluten modifies lipids. Am J Physiol Regul Integr Comp Physiol. 2023 Sep 1;325(3):R248-R259. doi: 10.1152/ajpregu.00016.2023. Epub 2023 Jul 3.

  PMID: 37399002 DERIVED

• Nordin E, Hellstrom PM, Brunius C, Landberg R. Modest Conformity Between Self-Reporting of Bristol Stool Form and Fecal Consistency Measured by Stool Water Content in Irritable Bowel Syndrome and a FODMAP and Gluten Trial. Am J Gastroenterol. 2022 Oct 1;117(10):1668-1674. doi: 10.14309/ajg.0000000000001942. Epub 2022 Aug 12.

  PMID: 36087104 DERIVED

• Nordin E, Brunius C, Landberg R, Hellstrom PM. Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial. Am J Clin Nutr. 2022 Feb 9;115(2):344-352. doi: 10.1093/ajcn/nqab337.

  PMID: 34617561 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

FODMAP Diet; Glutens

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Elimination Diets; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Officials

• Per Hellström, Prof

  Uppsala University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The study will be double-blinded. Neither the participant nor the care providers or the outcome assessor will know which treatment is which.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical doctor, Professor

Model Details: The study will be a double-blinded, randomized, placebo-controlled cross-over study.

Study Record Dates

• First Submitted: August 19, 2018
• First Posted: August 31, 2018
• Study Start: September 10, 2018
• Primary Completion: June 14, 2019
• Study Completion: June 14, 2019
• Last Updated: September 25, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: After September 2020.
• Access Criteria: Data sharing for supplement data on publication.

Locations

SE (1)