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

Study Purpose

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.#46; non- carriers (negative controls) and CSID subjects (positive controls), applying an MRI multiparametric test combined with a breath test.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06770907
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Nottingham
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Maura Corsetti, Medical Doctor
Principal Investigator Affiliation	University of Nottingham
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Sucrase Isomaltase Deficiency

Arms & Interventions

Arms

: Congenital Sucrase-Isomaltase Deficiency

Subjects with congenital sucrase-isomaltase deficiency (CSID) who report symptoms

: Healthy subjects

Subjects without CSID

: Asymptomatic controls single carriers

Subjects single carriers for sucrose isomaltase deficiency without symptoms

: Asymptomatic controls double carriers

Subjects double carriers for sucrose isomaltase deficiency without symptoms

Interventions

Other: - Blood, stool and saliva collection

Blood, stool and saliva collection

Other: - Questionnaire completion

Questionnaire on: - Hospital Anxiety and Depression Score (HADS) for adults - Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by CNAQ questionnaire for adults and children - Patient Health Questionnaire 12 (PHQ-12) Somatic Symptom scale

Diagnostic Test: - Magnetic Resonance Imaging (MRI) and Breath test

MRI scans and breath test samples collected after drink test with sucrose

Contact a Trial Team

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International Sites

University of Nottingham, Nottingham, United Kingdom

Status

Address

University of Nottingham

Nottingham, , NG7 2UH

Site Contact

Maura Corsetti, Medical Doctor

maura.corsetti@nottingham.ac.uk

0044 7976448821

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