Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity

NCT05795049 | Active Not Recruiting

• 2 other identifiers: 20GA093288003
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Irritable Bowel Syndrome (IBS); Sucrase Isomaltase Deficiency

Keywords

nutrigenetics; carbohydrates maldigestion

Outcome Measures

Primary Outcomes (1)

• number of IBS-D and IBS-M with of SI and CDG hypomorphic variants as compared to asymptomatic controls

  the prevalence of SI and CDG hypomorphic variants in IBS-D and IBS-M patients across countries and ethnicities, compared to asymptomatic controls

  baseline

Secondary Outcomes (14)

• Difference in age between patients carriers and non-carriers of defective (hypomorphic) gene

  baseline

• Difference in gender between patients carriers and non-carriers of defective (hypomorphic) gene

  baseline

• Difference in ethnicity between patients carriers and non-carriers of defective (hypomorphic) gene

  baseline

• Difference in IBS subtype between patients carriers and non-carriers of defective (hypomorphic) gene

  baseline

• Difference in post-infectious onset between patients carriers and non-carriers of defective (hypomorphic) gene

  baseline

Study Arms (2)

IBS Patient

IBS patient with diarrhoea or alternating bowel habit

Other: Stool and saliva sample collection; Other: Questionnaire completion

Healthy subject

Participants without IBS

Other: Stool and saliva sample collection; Other: Questionnaire completion

Interventions

Stool and saliva sample collection OTHER

Stool and saliva samples collection

Healthy subject; IBS Patient

Questionnaire completion OTHER

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®

Healthy subject; IBS Patient

Eligibility Criteria

• Age: 5 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Multicentre study. IBS patients identified through secondary and tertiary care gastroenterological clinics. Asymptomatic adult controls recruited at the same site as respective patients or, for instance, from transfusion clinics, blood donor centres, bowel cancer screening as long as data on the absence of symptoms is documented.

You may qualify if:

• 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

You may not qualify if:

• 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).
• Between 5 and 70 years of age
• Absence of Rome III IBS criteria
• 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).

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• CICbioGUNE: collaborator
• Christian-Albrechts-University of Kiel: collaborator
• University of Veterinary Medicine Hannover: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (17)

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• Husein DM, Naim HY. Impaired cell surface expression and digestive function of sucrase-isomaltase gene variants are associated with reduced efficacy of low FODMAPs diet in patients with IBS-D. Gut. 2020 Aug;69(8):1538-1539. doi: 10.1136/gutjnl-2019-319411. Epub 2019 Jul 22. No abstract available.

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Related Links

• Sponsor website page

Biospecimen

Retention: SAMPLES WITH DNA

Saliva and stool sample

MeSH Terms

Conditions

Irritable Bowel Syndrome; Sucrase-isomaltase deficiency, congenital

Interventions

Defecation

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: April 3, 2023
• Study Start: July 23, 2024
• Primary Completion: September 30, 2025
• Study Completion: March 31, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)