Genetic Carbohydrate Maldigestion As a Model to Study Food Hypersensitivity Mechanism and Guide Personalised Treatment Using a Non-invasive Multiparametric Test (WORK PACKAGE 2)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- University of Nottingham
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Area under the curve
Study Overview
Brief Summary
Irritable bowel syndrome (IBS) affects one in seven people with gastrointestinal (GI) symptoms that are detected without an established underlying organic cause. IBS strongly impacts quality of life, is a leading cause of work absenteeism, and consumes 0.5% of the healthcare annual budget. It manifests in women more than men with symptoms including abdominal pain, bloating, constipation (IBS-C), diarrhoea (IBS-D), and mixed presentations (IBS-M). The development of therapeutic options is hampered by the heterogeneity of IBS, the lack of specificity of its symptom-based definitions, and the poor understanding of the underlying pathophysiological mechanisms.
Many people with IBS find that certain foods (particularly carbohydrates) trigger their symptoms and avoiding such foods has been shown to be effective in IBS. An example of such a diet is the low-FODMAP (fermentable oligo-, di-, monosaccharides and polyols) exclusion diet, developed by researchers at Monash University. This has suggested that the food-symptom relation may involve malabsorption of carbohydrates due to inefficient enzymatic breakdown of polysaccharides. However, only a percentage of subjects respond to this diet. Overall, the current findings relating to SI, suggest a strong potential for effective personalized therapeutic (dietary) interventions in subgroups of IBS subjects and suggest similar mechanisms should be investigated in relation to other genes involved in the digestion and absorption of carbohydrates (CDGs). This project aims to understand what the mechanisms for GI symptoms in subjects with these genetic alterations are. Aim of the study is to assess the gut response to a sucrose challenge in single-and double-carriers of the common hypomorphic sucrase-isomaltase variant p. (Val15Phe) vs non- carriers (negative controls) and CSID subjects (positive controls), applying an MRI multiparametric test combined with a breath test.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Area under the curve
Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
Area under curve (AUC) of the change from baseline for the MRI measured small bowel water content after the drink test with sucrose
Secondary Outcomes
- Habitual diet questionnaire(during 4 days before the MRI study)
- MRI measured colon free water content(0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- MRI measured small bowel and colon volume(0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- Breath hydrogen and methane concentration measured in parts per million after drink test(baseline and then 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- Symptoms of nausea, gas/flatulence, bloating and pain/discomfort measured using a Composite Symptom Score after the drink test(0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by Comprehensive Nutrition Assessment Questionnaire(time 0)
- Hospital Anxiety and Depression Score(time 0)
- The Patient Health Questionnaire 12(Time 0)
- MRI measured small bowel and colon gas content(0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- MRI measured oro-caecal transit time(0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- Stool microbiota taxonomic(Up to 3 days before the MRI study)
- Stool microbiota alpha and beta diversity measurements(Up to three days before the MRI study day)
- Serum levels of short chain fatty acids(At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test)
- Circulating blood glucose levels(Baseline and then 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test)
- Serum levels of surrogates of intestinal permeability (occludin, lipopolysaccharide binding protein)(At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test)
- Serum levels of lipidome and free fatty acids(At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test)
- Serum levels of total serum N-glycome and glucose(At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test)
- Food and drink avoidance questionnaire(at time 0)
- Leeds Food Preference Questionnaire(at time 0)
- Food Craving Questionnaire - State (FCQ-S)(at time 0)
Investigators
Maura Corsetti
Associate Professor of Gastroenterology
University of Nottingham