Fructose and Fructans in Irritabla Bowel Syndrome

NCT01776853 | Completed

• 2 other identifiers: 1210212/EM/0443
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate if patients with Irritable Bowel Syndrome (IBS) who also report bloating are more likely to report clinically important gastrointestinal symptoms after consuming fructose or fructans than after consuming glucose. We will also use MRI imaging to investigate the mechanisms by which those symptoms might be caused. We will also study a parallel group of age and gender frequency matched healthy volunteers to provide descriptive statistics on a likely reference range for the healthy population. Irritable Bowel Syndrome (IBS) is a common chronic condition, the main features of which are pain in the abdomen, an erratic bowel habit and sometimes bloating. Recent research has found that certain carbohydrates (sugars) in the diet can cause symptoms such as discomfort, bloating and wind/gas in people with IBS. These sugars are not well digested in the small bowel. They move to the colon (large bowel) where bacteria act on them by fermentation, producing gas. Some of the gas is absorbed and breathed out through the lungs, where we can measure it. The rest is released as flatulence/ wind, or occasionally belching. People without IBS rarely get symptoms after consuming these sugars. We want to find out what is different in IBS sufferers. We will study fructose and fructans, sugars found in fruit, vegetables and wheat. Fructose draws water into the small bowel but fructans do not so we can compare effects on the small bowel and colon. Participants will attend three times, and on each occasion consume a drink containing either fructose, fructans, or glucose - a sugar that does not cause symptoms. Neither they nor the investigators present will know which drink is which. They will record their symptoms over the next 5 hours. We will observe how many report a clinically important increase in symptoms. To look at what is happening in the bowel we will use a technique called Magnetic Resonance Imaging (MRI). We want to see if more gas, or water, builds up in people with IBS than in healthy volunteers. We will also measure the amount of hydrogen released in the breath to see if this is could be a simple bedside test that agrees with the MRI findings Finding differences between the response of participants to fructose, fructans and glucose could change the way we advise patients, and could lead to the use of MRI as a test for IBS.

Conditions

Irritable Bowel Syndrome

Keywords

Irritable Bowel Syndrome; Fructose; Fructans; MRI; Fermentation; Breath Tests; Flatulence; Abdominal Pain; Diarrhoea

Outcome Measures

Primary Outcomes (1)

• Symptom response (yes/no)

  Clinically important GI symptoms (yes/no) reported by participants in the 5 hours after exposure. * We will measure 4 symptoms from a previously validated questionnaire (Suarez 1995) on a scale of 0 (none), 1 (mild/ distinct but negligible), 2 (moderate/ annoying), 3 (severe/ disabling) * Symptoms include abdominal pain, bloating, gas/flatulence, and diarrhoea. * We will add together scores for each symptom to get the total score (min 0; max 12) * We will define clinically important symptoms as an increase from baseline in additive total score of 3 or greater.

  At any point 0-5 hours after exposure

Secondary Outcomes (4)

• Symptom Intensity

  0-5 hours after intervention

• Breath Hydrogen

  0-5 hours after intervention

• Colonic Gas Volume

  0-5 hours after intervention

• Small Bowel Water Content

  0-5 hours after intervention

Study Arms (3)

Glucose

PLACEBO COMPARATOR

40g glucose in 500ml water flavoured with lime juice

Dietary Supplement: Glucose

Fructose

EXPERIMENTAL

40g fructose in 500ml water flavoured with lime juice

Dietary Supplement: Fructose

Fructans

EXPERIMENTAL

40g fructans in 500ml water flavoured with lime juice

Dietary Supplement: Fructans

Interventions

Glucose DIETARY_SUPPLEMENT

Glucose

Fructose DIETARY_SUPPLEMENT

Fructose

Fructans DIETARY_SUPPLEMENT

Fructans

Eligibility Criteria

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

You may qualify if:

• Patients who meet the Rome III research diagnostic criteria for IBS(Longstreth 2006) who also report bloating OR
• Healthy volunteers who do not meet Rome III clinical diagnostic criteria for IBS
• Aged 18-65
• Able to give informed consent

You may not qualify if:

• Any reported history of gastrointestinal surgery (excluding appendicectomy or cholecystectomy)
• Presence of an intestinal stoma
• Pregnancy declared by candidate
• Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
• Reported alcohol dependence
• Antibiotic or probiotic treatment in the past 4 weeks
• Inability to lie flat or exceed scanner limits of weight \<120kg
• Poor understanding of English language
• Participation of any medical trials for the past 3 months
• Judgement by the PI that the candidate who will be unable to comply with the full study protocol e.g. Diabetes, severe Chronic Obstructive Pulmonary Disease(COPD)

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (5)

• Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology. 1990 Oct;99(4):1016-20. doi: 10.1016/0016-5085(90)90621-7.

  PMID: 2394324 BACKGROUND

• Suarez FL, Savaiano DA, Levitt MD. A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance. N Engl J Med. 1995 Jul 6;333(1):1-4. doi: 10.1056/NEJM199507063330101.

  PMID: 7776987 BACKGROUND

• Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006 Apr;130(5):1480-91. doi: 10.1053/j.gastro.2005.11.061.

  PMID: 16678561 BACKGROUND

• Shepherd SJ, Parker FC, Muir JG, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol. 2008 Jul;6(7):765-71. doi: 10.1016/j.cgh.2008.02.058. Epub 2008 May 5.

  PMID: 18456565 BACKGROUND

• Major G, Pritchard S, Murray K, Alappadan JP, Hoad CL, Marciani L, Gowland P, Spiller R. Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome. Gastroenterology. 2017 Jan;152(1):124-133.e2. doi: 10.1053/j.gastro.2016.09.062. Epub 2016 Oct 14.

  PMID: 27746233 DERIVED

Related Links

• For more information on the NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham

MeSH Terms

Conditions

Irritable Bowel Syndrome; Flatulence; Abdominal Pain; Diarrhea

Interventions

Glucose; Fructose; Fructans

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Polysaccharides

Study Officials

• Robin C Spiller, MB BChir MSc MD FRCP

  NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham

  STUDY CHAIR

• Giles AD Major, BM BCh MA MRCP

  NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and the University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 23, 2013
• First Posted: January 28, 2013
• Study Start: January 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 13, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)