Brain and Gut Responses to Intragastric Administration of FODMAPs in Healthy Subjects and Patients With Irritable Bowel Syndrome

NCT04283487 | Completed

• 1 other identifier: FODMAP2
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Low fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) diet is taken as a possible strategy to improve symptoms in IBS patients. However, the gut-brain signalling mechanisms underlying this observation remain poorly understood. In this study, the investigators aim to study the brain mechanisms underlying the effect of intragastric administration of one specific FODMAP (fructans) on gastrointestinal and non- gastrointestinal symptom responses, changes in gut physiology(morphology of the gut, water content and intestinal motility), and to relate the findings to changes in gastrointestinal peptides. Intragastric administration of three different solutions will be given after an overnight fast: one FODMAP solution (fructans), a positive control (glucose) and a negative control (saline). The whole procedure consists of a functional magnetic resonance imaging (fMRI) and abdominal MRI examination, and will take approximately four hours. The participants will undergo the fMRI for one hour for assessing brain activity, during which blood samples will be collected. The abdominal MRI will be performed at 1-hour interval for three hours to assess pre and post stimulated changes in gut physiology, specifically the morphology of the gut water content and pan-intestinal motility. During the whole procedure, questionnaires for assessing the gastrointestinal symptoms and emotional state will be collected. The investigators hypothesise that fructans induce distension and increased sensations of pain, cramps and flatulence in the IBS group more than the HC. Furthermore, this will be associated with increased activation of pain-responsive brain regions in IBS compared to HC, which will be mediated by differential changes in gut peptide levels (↓ in orexigenic and ↑ in anorexigenic hormones).

Conditions

Irritable Bowel Syndrome

Keywords

FODMAP; Irritable bowel syndrome; brain-gut axis; fMRI; abdominal MR

Outcome Measures

Primary Outcomes (1)

• Change in brain activation patterns measured by fMRI

  change in blood oxygenation level dependent (BOLD) signal by fMRI

  -10 min to 50 min

Secondary Outcomes (11)

• Change in gastrointestinal symptom scores measured by VAS

  -30 min to 180 min

• Change in state emotion score measured by validated questionnaire

  -30 min to 180 min

• Change in state emotion score measured by validated questionnaire

  -30 min to 180 min

• Change in plasma levels of gut peptides

  -20 min to 60 min

• Change in plasma levels of gut peptides

  -20 min to 60 min

Study Arms (3)

Fructans solution

EXPERIMENTAL

Fructans (FODMAP) are oligosaccharides containing fructose chains. Since the human body lacks hydrolases to break down these saccharides, fructans are poorly absorbed molecules in everybody.The fructans solution used in this study is 500 ml water containing 40g fructans

Dietary Supplement: Fructans

Glucose solution

ACTIVE COMPARATOR

Glucose is a carbohydrate that is not classified as FODMAP, and is therefore used as a positive control in this study. The glucose solution used in this study is 500 ml water containing 40g glucose.

Dietary Supplement: Glucose

Saline solution

PLACEBO COMPARATOR

The saline solution does't contain any sugar and used in this study is 500ml 0.9% normal saline.

Dietary Supplement: Saline

Interventions

Fructans DIETARY_SUPPLEMENT

500ml 0.9% normal saline containing 40g fructans

Fructans solution

Glucose DIETARY_SUPPLEMENT

500ml 0.9% normal saline containing 40g glucose

Glucose solution

Saline DIETARY_SUPPLEMENT

500ml 0.9% normal saline

Saline solution

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No symptoms or history of gastrointestinal disease or disorder, other significant diseases
• Female
• Age 18 - 55 years
• Body Mass Index (BMI) of 19 - 28 kg/m2
• Stable body weight for at least 3 months prior to the start of the study
• Right-handed or ambi-dexter

You may not qualify if:

• Medical
• Abdominal or thoracic surgery. Exception: appendectomy
• Gastrointestinal, endocrine or neurological diseases
• Cardiovascular, respiratory, renal or urinary diseases
• Hypertension
• Food or drug allergies
• Anemia Psychiatric disorders
• Eating disorders
• Depressive disorders
• Anxiety disorders
• Psychotic disorders Medication use
• No regular medication affecting CNS or GI system (oral contraception accepted) Other
• Conditions that can interfere with functional magnetic resonance imaging (fMRI), e.g. cochlear implants, metal fragments or metal implants in the body, pacemaker, neural stimulator, …
• No history of cannabis use or any other drug of abuse for at least 12 months prior to the study
• Alcohol abuse (more than 14 units for woman per week)

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

KU Leuven

Leuven, 3000, Belgium

Location

Related Publications (1)

• Wu J, Masuy I, Biesiekierski JR, Fitzke HE, Parikh C, Schofield L, Shaikh H, Bhagwanani A, Aziz Q, Taylor SA, Tack J, Van Oudenhove L. Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome. Aliment Pharmacol Ther. 2022 Mar;55(6):670-682. doi: 10.1111/apt.16812. Epub 2022 Feb 15.

  PMID: 35166384 DERIVED

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Fructans; Glucose; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Polysaccharides; Carbohydrates; Hexoses; Monosaccharides; Sugars; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jan Tack, MD, PHD

  UZ Leuven / KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, double-blind, placebo-controlled, crossover

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 25, 2020
• Study Start: February 22, 2018
• Primary Completion: August 10, 2019
• Study Completion: August 10, 2019
• Last Updated: May 28, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Deidentified individual participant data that underlie the reported results will be made available 3 months after publication for a period of 5 years after the publication date upon request.

Locations

BE (1)