Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity

Not yet recruiting

• Conditions: Sucrase Isomaltase Deficiency; Irritable Bowel Syndrome (IBS)
• Interventions: Other: Stool and saliva sample collection; Other: Questionnaire completion

• Registration Number: NCT05795049
• Lead Sponsor: Nottingham University Hospitals NHS Trust

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-23
• Study First Submitted QC: 2023-03-29
• Study First Posted: 2023-04-03
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-19
• Last Update Posted: 2024-06-21
• Study Start: 2024-08
• Primary Completion: 2025-04-30
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Not provided

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Exclusion Criteria

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy subject	Stool and saliva sample collection	Participants without IBS
IBS Patient	Stool and saliva sample collection	IBS patient with diarrhoea or alternating bowel habit
IBS Patient	Questionnaire completion	IBS patient with diarrhoea or alternating bowel habit
Healthy subject	Questionnaire completion	Participants without IBS

Primary Outcome Measures

Name	Time	Method
number of IBS-D and IBS-M with of SI and CDG hypomorphic variants as compared to asymptomatic controls	baseline	the prevalence of SI and CDG hypomorphic variants in IBS-D and IBS-M patients across countries and ethnicities, compared to asymptomatic controls

Secondary Outcome Measures

Name	Time	Method
Difference in IBS subtype between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - number of patients with IBS with diarrhoea (IBS-D) and with mixed bowel habit (IBS-M)
Difference in symptoms presentations between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - IBS symptoms severity score for adults. This score range between 0 and 500 and a change of at least 50 is considered a clinically relevant change.
Difference in symptoms between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - GI symptoms using those reported in the Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms Module
Difference in age between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - age in years
Difference in ethnicity between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - ethnicity
Difference in somatisation between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - Somatization score for adults. a score of 5, 10, and 15 represent cutpoints for low, medium, and high somatic symptom severity, respectively.
Difference in gender between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - gender
Difference in post-infectious onset between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - number of patients with post-infectious onset
Difference in anxiety and depression between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - Hospital Anxiety and Depression score for adults. A score up to 7 for anxiety and or depression is considered Normal; between 8-10 Borderline abnormal (borderline case) and between 11-21 = Abnormal (case)
Difference in habitual intake of sugars between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by CNAQ questionnaire for adults and children
Difference in number of previous abdominal surgery between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - number of patients with IBS with previous abdominal surgery
Difference in quality of life between patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - Quality of Life as measured by the Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms (PedsQL™ GI Symptoms) Scale. The high.er the PedsQL score, the better the quality of life
Difference in anxiety and depression between paediatric patients carriers and non-carriers of defective (hypomorphic) gene	baseline	Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene: - Anxiety, Depression as measured by the Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS®). This use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.; On the T-score metric: A score of 40 is one SD lower than the mean of the reference population. A score of 60 is one SD higher than the mean of the reference population.
Difference in in vitro SI enzyme activity in human cells with defective gene as compare with those with normal gene	baseline	Difference in the intensity of the SI protein bands of immunoprecipitations of monoclonal anti-SI antibodies that recognize different conformations of the SI protein

Trial Locations

Locations (1)

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, United Kingdom