Effects of FODMAPs on Small Bowel Water Content: an MRI Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01459406
First received: October 21, 2011
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

Some carbohydrates, particularly fructose, the sugar found in fruit and bread may cause bloating, pain and erratic bowel habits (diarrhoea and constipation) particularly in patients suffering from the irritable bowel syndrome (IBS). This may be because they are not well absorbed in the small intestine and cause water to be trapped in the bowel causing distension. Studies have shown that reducing the amount of these sugars in the diet can relieve these symptoms. There is some evidence that combining fructose and glucose can reduce the symptoms caused by fructose but just why is unclear. In this study, the investigators will use a non invasive medical imaging technique called "magnetic resonance imaging" (or MRI) to look at the behaviour of drinks containing these sugars in the bowels of healthy human volunteers.

The investigators will give four different drinks: one beverage consisting of a very well absorbed sugar, glucose, another consisting of the less well absorbed sugar fructose, a third which is a mixture of glucose and fructose, and a fourth consisting of several fructose subunits joined together (called fructan). The investigators will take MRI images of the stomach and intestines at intervals for 5 hours and compare these with the feelings of distension and bloating in our volunteers. The results will act as control for subsequent studies in IBS patients and these may help design diets to reduce symptoms in IBS.


Condition Intervention
Healthy
Dietary Supplement: Glucose
Dietary Supplement: Fructose
Dietary Supplement: Fructan
Dietary Supplement: Fructose and glucose

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Effects of FODMAPs (Fermentable Oligo-, Di-, and Mono-saccharides, And Polyols) on Small Bowel Water Content: an MRI Study

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • small bowel water content area under the curve [ Time Frame: -45 min to 315 min ] [ Designated as safety issue: No ]
    Area Under the curve for small bowel water content, methods as Marciani, L., et al., Gastroenterology, 2010. 138(2): p. 469-U90. Hoad, C.L., et al.,. Physics in Medicine and Biology, 2007. 52(23): p. 6909-6922.


Secondary Outcome Measures:
  • gastric emptying T50 [ Time Frame: -45 min to 315 min ] [ Designated as safety issue: No ]
    time to half empty the stomach

  • ascending colon volume [ Time Frame: -45 min to 315 min ] [ Designated as safety issue: No ]
    AUC of the geometric volume of the ascending colon

  • ascending colon motility [ Time Frame: -45 min to 315 min ] [ Designated as safety issue: No ]
    motility index of the ascending colon as determined from dynamic MRI scan

  • symptoms questionnaires [ Time Frame: -45 min to 315 min ] [ Designated as safety issue: No ]
    bloating, nausea, gas belching and abdominal pain

  • bowel transit time [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    first time to detect sweetcorn markers in the stool

  • fecal tryptase activity [ Time Frame: 24 h ] [ Designated as safety issue: No ]
    activity of stool triptase in trypsin units of activity


Enrollment: 17
Study Start Date: October 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Glucose drink
Serial MRI of the gastrointestinal tract upon 500 ml water drink containing 40g glucose
Dietary Supplement: Glucose
500 ml water drink containing 40g glucose
Experimental: Fructose drink
Serial MRI of the gastrointestinal tract upon 500 ml water drink containing 40g fructose
Dietary Supplement: Fructose
500 ml water drink containing 40g fructose
Experimental: Fructan drink
Serial MRI of the gastrointestinal tract upon 500 ml water drink containing 40g fructan
Dietary Supplement: Fructan
500 ml water drink containing 40g fructan
Experimental: Fructose and glucose drink
Serial MRI of the gastrointestinal tract upon 500 ml water drink containing 40g fructose and 40 g glucose
Dietary Supplement: Fructose and glucose
500 ml water drink containing 40g fructose and 40g glucose

Detailed Description:

Title: Effects of FODMAPs (Fermentable Oligo-, Di-, and Mono-saccharides, And Polyols) on small bowel water content: an MRI study

  1. Background. FODMAPs consist of fructose, lactose, fructo- and galacto-oligosaccharides such as fructans and galactans, and polyols such as sorbitol and mannitol. These carbohydrates are poorly absorbed in the small intestine and have been shown to trigger symptoms of irritable bowel syndrome (IBS). Previous studies have shown that fructose malabsorption results in an increased osmotic load in the small bowel, which can have a laxative effect. Physical proof of this has only been obtained using an ileostomy model on patients. This study indicated increased small bowel water content (SBWC) but this has never been established in intact humans .). We have been using noninvasive magnetic resonance imaging (MRI) to provide novel insights on the fate of food materials within the gastro-intestinal tract (GIT) of humans for the last decade.
  2. Aims (to include hypothesis to be tested) This study aims to investigate whether fructose alone will increase SBWC compared to an equivalent mass of glucose, and if adding glucose to fructose will reduce its effect on the SBWC. The study also aims to determine if fructans alter colonic transit.The main hypothesis is that fructose will increase small bowel water while fructans will mainly affect colonic transit..
  3. Experimental protocol and methods. A single-centre, randomized, cross-over design study consisting of a screening visit and four test days, which will be approximately 1 week apart The subjects (18 healthy volunteers for main study plus 4 for pilot studies) will receive (according to a randomization schedule) each test day one out of four test products: 1) glucose (control) 2) fructose, 3) glucose with fructose and 4) fructans. On each test day, volunteers will have a baseline scan in a 1.5T scanner, consume one of the products instead of breakfast at 09:00 and will be imaged in the scanner at intervals for 5 hours using a range of MRI sequences.

All the tested ingredients are food grade, have a history of safe use at intended usage levels, and are regarded as safe.

Four test products will be evaluated:

  1. 500 mL of glucose (40g of glucose dissolved in water with pure lime juice as flavorant)
  2. 500 mL fructose (40g fructose dissolved in water with pure lime juice as flavorant)
  3. 500 mL of glucose with fructose (40g glucose and 40g fructose dissolved in water with pure lime juice as flavorant, 40 or 80 gm)
  4. 500 mL fructan (40g of 100% fructan (inulin) dissolved in water with pure lime juice as flavorant)

4. Measurable end points/statistical power of the study. Primary endpoint: small bowel water content area under the curve (AUC) -45 - 315 minutes. Secondary endpoint: gastric emptying T50, colonic volume as characterised by AUC -45 - 315 minutes of ascending colon, colonic motility, symptoms questionnaires, small bowel transit time, breath hydrogen concentrations and tryptase faecal content.

Previous work using mannitol and glucose indicates that mean (SD) SBWC at 40 minutes postprandial after ingesting 300ml glucose was 47 (SD 15) and using n=12 the investigators calculate the investigators can detect an increase of 20 ml in excess of this with 90% power which is very much less than the investigators are predicting. The investigators plan to use 18 to ensure the investigators can assess our secondary endpoints for which there is no data with which to perform a power calculation.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Apparently healthy: no medical conditions which might effect study measurements.
  • No reported participation in another nutritional or biomedical trial 3 months before the pre-study examination or during the study.
  • Age ≥ 18 and ≤ 60 year at pre-study investigation.
  • Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2
  • No reported participation in night shift work two days prior to pre-study investigation or during the study. Night work is defined as working between midnight and 6.00 AM.
  • Strenuous exercise ≤ 10 hours per week.
  • Gender: male or female
  • Consumption of ≤ 21 alcoholic drinks in a typical week
  • Currently not smoking
  • Suitable for MRI scanning (e.g., absence of metal implants, infusion pumps and pacemakers) as assessed by the attached MRI safety questionnaire.

Exclusion Criteria:

  • - use of medication which interferes with study measurements or bowel motility (as judged by the study physician).
  • Antibiotics in the 3 weeks before pre-study examination
  • Probiotics or during the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459406

Locations
United Kingdom
NDDC BRU and Sir Peter Mansfield Magnetic Resonance Centre
Nottingham, Nottinghamshire, United Kingdom, NG72UH
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Robin C Spiller, MD FRCP University of Nottingham
  More Information

Publications:

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01459406     History of Changes
Other Study ID Numbers: L/7/2011
Study First Received: October 21, 2011
Last Updated: December 18, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
Gastrointestinal physiology
Gastrointestinal response to sugars
MRI
gastrointestinal
stomach
small bowel
colon
glucose
fructose
fructan
FODMAP

Additional relevant MeSH terms:
Levan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014