Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity

Study Purpose

Irritable bowel syndrome (IBS) affects one in seven people with gastrointestinal (GI) symptoms. 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) (1). The development of therapeutic options is hampered by the poor understanding of the underlying cause of symptoms. Many patients find that certain foods (particularly carbohydrates) trigger their symptoms, and avoiding such foods has been shown effective in IBS, like in the low-FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) exclusion diet. This has suggested that the food-symptom relation may involve malabsorption of carbohydrates due to inefficient digestion. However only a percentage of patients respond to this diet. Recently it has been reported that a subset of IBS carries hypomorphic (defective) gene variant of the sucrase isomaltase (SI), the enzyme that normally digests carbohydrates, sucrose and starch. This carbohydrate maldigestion (the breakdown of complex carbohydrates by a person's small bowel enzymes) is characterized by diarrhoea, abdominal pain and bloating, which are also features of IBS. This possibly occurs via accumulation of undigested carbohydrates in the large bowel, where they cause symptoms due to gas production following bacterial fermentation. Similar mechanisms may be acting at the level of other enzymes involved in the digestion, breakdown and absorption of carbohydrates (carb digestion genes -CDGs). Aim of the study is to study the prevalence of this genetic alteration in a large number of IBS patients as compared to asymptomatic controls.

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	5 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria for Patients:

- Patients age between 5 and 70 years of age.

- Patients with IBS-D or IBS-M as defined by the Rome III criteria.

- Previous negative endoscopy with biopsies excluding IBD or microscopic colitis in patients above 50 years old.

- Negative relevant additional screening or consultation whenever appropriate.

- Ability to conform to the study protocol.

Exclusion Criteria for Patients:

- Patients with IBS-C or IBS-U according to Rome III criteria.

- Patients with any condition which, in the opinion of the investigator, makes the patient unsuitable for participation in the study.

- Patients on opioids.

- Patients with concurrent organic gastrointestinal disease (inflammatory bowel disease, celiac disease, cancer), or a major disease such as diabetes, uncontrolled thyroid disease.

- Patients with a history of bowel surgery (not appendectomy or cholecystectomy) - Concurrent major confounding condition, e.g. alcohol or substance abuse in the last 2 years (clinician's judgement).

Inclusion Criteria for healthy controls:

- Between 5 and 70 years of age.

- Absence of Rome III IBS criteria.

Exclusion Criteria for healthy controls:

- Blood relatives of the participating IBS patient are not allowed to participate.

- Person with any condition which, in the opinion of the investigator, makes them unsuitable for participation in the study.

- 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).

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.	NCT05795049
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.	Nottingham University Hospitals NHS Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Irritable Bowel Syndrome (IBS), Sucrase Isomaltase Deficiency
Study Website:	View Trial Website

Arms & Interventions

Arms

: IBS Patient

IBS patient with diarrhoea or alternating bowel habit

: Healthy subject

Participants without IBS

Interventions

Other: - Stool and saliva sample collection

Stool and saliva samples collection

Other: - Questionnaire completion

Questionnaire on; demographic, ethnicity, IBS subtype, post-infection onset, previous surgeries IBS severity score for adults Hospital Anxiety and Depression scores for adults Somatization score 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 Quality of Life as measured by the PedsQL™ GI Symptoms Module GI symptoms as measured by the PedsQL™ GI Symptoms Module Anxiety, Depression as measured by the Pediatric PROMIS®

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Maura Corsetti, MD

maura.corsetti@nottingham.ac.uk

07976448821

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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