Clinical trial NCT06770907: Genetic Carbohydrate Maldigestion As Model to Study Food Hypersensitivity Mechanism (WORK PACKAGE 2)
Official title: Genetic Carbohydrate Maldigestion As a Model to Study Food Hypersensitivity Mechanism and Guide Personalised Treatment Using a Non-invasive Multiparametric Test (WORK PACKAGE 2)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Sucrase Isomaltase Deficiency
Keywords: sucrose isomaltase deficiency
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: cic bioGune
name: Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel
name: University of Veterinary Medicine Hannover
First posted: 2025-01-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Single-centre study. CSID subjects will be identified and recruited either with the help of the PPI group through advertisements on social media or flyers at Clinical Genetics and Genomic Conferences and Adult Metabolic Disorder Conferences.

Healthy participants will be recruited through social media advertisements and posters.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the curve
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
Secondary outcomes:
measure: Habitual diet questionnaire
timeFrame: during 4 days before the MRI study
measure: MRI measured colon free water content
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: MRI measured small bowel and colon gas content
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: MRI measured small bowel and colon volume
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: MRI measured oro-caecal transit time
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: Breath hydrogen and methane concentration measured in parts per million after drink test
timeFrame: baseline and then 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: Symptoms of nausea, gas/flatulence, bloating and pain/discomfort measured using a Composite Symptom Score after the drink test
timeFrame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by Comprehensive Nutrition Assessment Questionnaire
timeFrame: time 0
measure: Hospital Anxiety and Depression Score
timeFrame: time 0
measure: The Patient Health Questionnaire 12
timeFrame: Time 0
measure: Stool microbiota taxonomic
timeFrame: Up to 3 days before the MRI study
measure: Stool microbiota alpha and beta diversity measurements
timeFrame: Up to three days before the MRI study day
measure: Serum levels of short chain fatty acids
timeFrame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test
measure: Circulating blood glucose levels
timeFrame: Baseline and then 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test
measure: Serum levels of surrogates of intestinal permeability (occludin, lipopolysaccharide binding protein)
timeFrame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test
measure: Serum levels of lipidome and free fatty acids
timeFrame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test
measure: Serum levels of total serum N-glycome and glucose
timeFrame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test
measure: Food and drink avoidance questionnaire
timeFrame: at time 0
measure: Leeds Food Preference Questionnaire
timeFrame: at time 0
measure: Food Craving Questionnaire - State (FCQ-S)
timeFrame: at time 0
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
affiliation: University of Nottingham
name: Maura Corsetti, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
References: