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

N/ANot Yet RecruitingNCT06770907

University of Nottingham80 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

Conditions

Sucrase Isomaltase Deficiency

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria for CSID subjects: * Aged ≥18 (all groups) * Subjects with genetically proven CSID * Previous negative endoscopy with biopsies excluding IBD or microscopic colitis in people above 50 years old. * Negative relevant additional screening (including exclusion of coeliac disease with TTG and IgA) * Ability to conform to the study protocol including the sucrose challenge. Exclusion Criteria for CSID subjects: * Subjects on opioids and use of drugs known to alter GI motility for the duration of the study. * Presence of concurrent organic gastrointestinal disease (inflammatory bowel disease, coeliac disease, cancer), or a major disease such as diabetes, uncontrolled thyroid disease * Any history of bowel surgery (not appendectomy or cholecystectomy) * Contraindication to MRI scanning * Having taken part in another interventional research study within 3 months * Concurrent major confounding condition (e.g. alcohol or substance abuse in the last 2 years) based on the study clinician's judgement. Inclusion Criteria for healthy participants: * Aged ≥18 years * Absence of Rome III IBS criteria * Non-SI variant confirmed (group 1) or Single-SI variants confirmed (group 2) or Double - SI variants confirmed (group 3) * Ability to conform to the study protocol including the sucrose challenge Exclusion Criteria for healthy participants: * Person presenting with a functional or organic GI disorder. * Person presenting with underlying disease that may involve the GI tract (e.g. Parkinson's disease) or be associated with GI symptoms (e.g. anorexia nervosa, major depression). * Any history of bowel surgery (not appendectomy or cholecystectomy) * Contraindication to MRI scanning * Having taken part in another interventional research study within 3 months * Concurrent major confounding condition (e.g. alcohol or substance abuse in the last 2 years) based on the clinician's judgement.

Outcomes

Primary Outcomes

Area under the curve

Area under curve (AUC) of the change from baseline for the MRI measured small bowel water content after the drink test with sucrose

Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

Secondary Outcomes

Habitual diet questionnaire

subject will report food eaten at each meal

Time frame: during 4 days before the MRI study

MRI measured colon free water content

MRI measured colon free water content, (in arbitrary units) after the drink test

Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

MRI measured small bowel and colon gas content

small bowel and colon gas content (in arbitrary units) after the drink test

Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

MRI measured small bowel and colon volume

small bowel and colon volume in arbritary units after drink test

Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

MRI measured oro-caecal transit time

oro-caecal transit time (OCTT), (in arbitrary units) after the drink test

Time frame: 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

Time frame: 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

Time frame: 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

CNAQ questionnaires results

Time frame: time 0

Hospital Anxiety and Depression Score

scale measuring the score of anxiety and depression

Time frame: time 0

The Patient Health Questionnaire 12

Scale measuring the psychosomatic score

Time frame: Time 0

Stool microbiota taxonomic

Analysis of of microbiota taxonomic in the two stool samples collected by patient during the day before the MRI study day

Time frame: Up to 3 days before the MRI study

Stool microbiota alpha and beta diversity measurements

Analysis of alfa and beta diversity of microbiota in the two stool samples collected by patient before the study day

Time frame: Up to three days before the MRI study day

Serum levels of short chain fatty acids

Serum levels

Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

Circulating blood glucose levels

Time frame: 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)

Serum levels

Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

Serum levels of lipidome and free fatty acids

Serum levels

Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

Serum levels of total serum N-glycome and glucose

Serum levels

Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

Food and drink avoidance questionnaire

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)

Time frame: at time 0

Leeds Food Preference Questionnaire

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.

Time frame: at time 0

Food Craving Questionnaire - State (FCQ-S)

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.

Time frame: at time 0

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts