Genetic Carbohydrate Maldigestion As Model to Study Food Hypersensitivity Mechanism (WORK PACKAGE 2)

Not yet recruiting

• Conditions: Sucrase Isomaltase Deficiency

• Registration Number: NCT06770907
• Lead Sponsor: University of Nottingham

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-21
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-13
• Last Update Posted: 2025-01-13
• Study Start: 2025-03
• Primary Completion: 2025-12
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Area under the curve	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 Outcome Measures

Name	Time	Method
MRI measured oro-caecal transit time	0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test	oro-caecal transit time (OCTT), (in arbitrary units) after the drink test
Stool microbiota taxonomic	Up to 3 days before the MRI study	Analysis of of microbiota taxonomic in the two stool samples collected by patient during the day before the MRI study day
Stool microbiota alpha and beta diversity measurements	Up to three days before the MRI study day	Analysis of alfa and beta diversity of microbiota in the two stool samples collected by patient before the study day
Serum levels of short chain fatty acids	At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test	Serum levels
Habitual diet questionnaire	during 4 days before the MRI study	subject will report food eaten at each meal
MRI measured colon free water content	0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test	MRI measured colon free water content, (in arbitrary units) 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	small bowel and colon volume in arbritary units after 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	CNAQ questionnaires results
Hospital Anxiety and Depression Score	time 0	scale measuring the score of anxiety and depression
The Patient Health Questionnaire 12	Time 0	Scale measuring the psychosomatic score
MRI measured small bowel and colon gas content	0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test	small bowel and colon gas content (in arbitrary units) 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
Serum levels of lipidome and free fatty acids	At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test	Serum levels
Serum levels of total serum N-glycome and glucose	At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test	Serum levels
Food and drink avoidance questionnaire	at time 0	patients will respond to the below questions: * Name of the food or drink you try to avoid.; * Please tell us if you try to avoid this food or drink partially or completely? Approximately how long you have tried to avoid this food or drink partially or completely.; Why do you try to avoid this food or drink partially or completely (including if you have been told to avoid it by a health care professional such as a doctor or dietitian)
Leeds Food Preference Questionnaire	at time 0	The LFPQ consists of two tasks requiring different interaction from the participant. One task requires an explicit evaluation of each food item using visual analogue scales. The other requires a quick choice to be made between paired combinations of foods. The order of task completion is randomised.
Food Craving Questionnaire - State (FCQ-S)	at time 0	participants respond to 14 questions about sugary food and they will respond with a scale from 1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree.

Trial Locations

Locations (1)

University of Nottingham; 🇬🇧 Nottingham, United Kingdom