Fructose Breath-testing in Irritable Bowel Syndrome (IBS)

Sponsor

Brain-Gut Research Group (Other)

Overall Status

Completed

CT.gov ID

NCT02614313

Collaborator

New Jersey Medical School (Other), National University, Singapore (Other)

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: Breath testing for food intolerances is becoming routine in patients with functional gastrointestinal disorders (FGID). Both FGID and saccharide intolerances (FODMAPs: fermentable oligo-, di-, polysaccharide and polyols, e.g. lactose, fructose, sorbitol) are common (>10% of any given population) and often respond to dietary modification. The breath tests are based on quantification of gas excretion in breath as a sign of malabsorption and symptom provocation, but are likely subject to considerable psychological bias. The role of expectation and other psychological effects on breath testing has not been reported, but is crucial for the validation of these increasingly wide-spread tests with considerable dietary and potentially deleterious consequences. Fructose has been shown to result in short term pro-inflammatory metabolic responses, but these effects have not been studied as underlying causes for intolerance symptoms in fructose intolerant patients with FGID.

Aim: To investigate the psychological component and the short-term metabolic effects of fructose breath testing in patients referred for evaluation of FGID using placebo. Additionally, to assess baseline predictors for a positive breath test result.

Methods: Fructose intolerance (defined by a positive symptom index) and malabsorption (defined by increased breath hydrogen/methane concentrations) will be determined in 30 successive male and female FGID in a single centre using breath-testing. Fructose 35g, given double-blind as well as open, a sweet placebo (cyclamate/saccharine; Assugrin®) and a neutral (still water) placebo given double-blind will be compared in a randomized, cross-over sequence and according to our standardised procedure on four separate study days. Symptoms will be recorded using standardised questionnaires and breath concentrations of H2 and CH4 will be measured during testing on the four study days. Somatisation and psychological profiles will be assessed by questionnaires. Blood samples will be obtained before and during provocation testing to assess short-term responses to fructose loading by metabolomics. Fructose, blinded and open, and placebo responses will be compared and baseline predictors for a positive breath tests assessed.

Condition or Disease	Intervention/Treatment	Phase
Functional Gastrointestinal Disorders Irritable Bowel Syndrome	Procedure: Open breath test with fructose Procedure: Breath test with sweet placebo (Assugrin) Procedure: Breath test with neutral placebo (still water) Procedure: Blinded breath test with fructose	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Diagnostic

Official Title:

Assessment of Psychological and Metabolic Responses During Fructose Intolerance Breath Tests in Patients With Functional GI Disorders: Placebo-controlled Breath Testing

Study Start Date :

Jun 1, 2016

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fructose double-blind Fructose during breath test, double-blind 35g	Procedure: Blinded breath test with fructose Double-blind randomised fructose 35g during breath test
Active Comparator: Fructose open Fructose during breath test, open 35g	Procedure: Open breath test with fructose Open randomised fructose 35g during breath test
Placebo Comparator: Sweet placebo double-blind Assugrin during breath test double-blind	Procedure: Breath test with sweet placebo (Assugrin) Double-blind randomised breath-testing with sweet placebo (Assugrin)
Placebo Comparator: Neutral placebo double-blind Water during breath test double-blind	Procedure: Breath test with neutral placebo (still water) Double-blind randomised breath-testing with neutral placebo

Outcome Measures

Primary Outcome Measures

Fructose intolerance, as percentage of patients [5 hours]
Defined by symptom scores

Secondary Outcome Measures

Between-group comparisons of breath test gas concentrations and symptom indices [5 hours]
Breath gas concentrations and cumulative symptoms experienced during breath testing will be compared between treatment groups
Correlations between breath test gas concentrations, symptom indices and metabolite [5 hours]
Correlations between changes in gas levels, GI symptoms from baseline and changes in metabolites identified by metabolomic analysis in the different treatment and responder groups (i.e intolerance or no intolerance as defined by the standard breath test results). Metabotype and psychological predictors at baseline for intolerance (responder) status during breath testing will be assessed by multiple regression analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria

Thirty male or female FGID (Irritable Bowel Syndrome or Functional Dyspepsia according to the Rome III criteria) patients -
10 healthy female and male controls
aged between 18 and 60 years

Exclusion criteria:

Bowel resections, except appendicectomy or cholecystectomy
Evidence of organic disease
No medications (excluding antihypertensives, antidepressants and low-dose aspirin), including herbal, from 4 days before the first study day until after breath test
Coeliac's disease