Brain and Gut Responses to Intragastric Administration of FODMAPs in Healthy Subjects and Patients With Irritable Bowel Syndrome
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome
Study type: Interventional

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).
    

Detailed description: 
      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.

      This is a randomised, double-blinded, crossover study. Eligible participants will come three
      times to the clinic after an overnight fast, for intragastric infusion of fructans (40g in
      500 ml water), glucose(40g in 500ml water) or saline(0.9% 500ml normal saline). The infusions
      will be given in counterbalanced order and with a washout period of at least one week.
      Participants and investigators will be blinded to the nature of the test solution, which will
      be made by a colleague unrelated to the study. The order of the test solutions will be
      determined by a computer-generated list. All participants will be asked to follow the low
      FODMAP diet for the 24 hours prior to each study day. Participants will be asked to record
      their food intake during the day to check their FODMAP intakes were reduced.

      To begin, the participants will have a nasogastric feeding tube placed and an intravenous
      cannula inserted in the non-dominant arm to facilitate repeated blood sampling. Fifteen
      minutes later, they will enter the MR scanner for a 5 minute adaptation period. Participants
      will complete visual analogue scales (VAS) on appetite-related sensations and GI symptoms and
      blood samples will be collected for gut peptide analysis. Current emotional state will be
      rated before and after scanning using the PANAS, and during scanning using the POMS. The
      abdominal MRI scan will begin after the adaption period and will take 10 minutes. Hereafter,
      brain scanning will be performed, starting with a baseline brain scanning period of 10
      minutes. After the baseline scanning, 500 mL of one of the three solutions will be infused as
      the functional brain imaging begins (and continues for 50 minutes). The VAS ratings will be
      collected every 10 minutes and blood samples will be collected every 20 minutes for measuring
      of ghrelin, CCK, GLP-1, motilin, and PYY, insulin and glucose throughout the scan. At 60
      minutes post-infusion, a 10 minute abdominal scan will be acquired. After that, the subject
      leaves the scanner and the catheter will be removed. The subject will remain at the facility
      for a 2 hour follow-up during which the VAS ratings will be collected every 30 minutes and an
      abdominal MRI will be performed at 120 minutes post infusion. After the last abdominal MRI
      scan is performed, the infusion tube will be removed and the participant can go home.
    

Intervention name(s): Fructans; Glucose; Saline
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 500ml 0.9% normal saline containing 40g fructans; 500ml 0.9% normal saline containing 40g glucose; 500ml 0.9% normal saline
Intervention MeSH terms: Levan
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomised, double-blind, placebo-controlled, crossover
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: FODMAP; Irritable bowel syndrome; brain-gut axis; fMRI; abdominal MR