Fructose Breath-testing in Irritable Bowel Syndrome (IBS)

Study Overview
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Brief Summary
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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.

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

Conditions
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Functional Gastrointestinal Disorders, Irritable Bowel Syndrome

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fructose intolerance, as percentage of patients | Defined by symptom scores | 5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group comparisons of breath test gas concentrations and symptom indices | Breath gas concentrations and cumulative symptoms experienced during breath testing will be compared between treatment groups | 5 hours | 
| Correlations between breath test gas concentrations, symptom indices and metabolite | 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. | 5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fructose, Irritable Bowel Syndrome, Breath test, Placebo