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NCT Number: NCT06770907

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Blood, stool and saliva collection

Other

Blood, stool and saliva collection

questionnaire completion

Other

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

Magnetic Resonance Imaging (MRI) and Breath test

Diagnostic Test

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

Primary outcomes

  1. Area under the curve

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

    Area under curve (AUC) of the change from baseline for the MRI measured small bowel water content after the drink test with sucrose

Secondary outcomes

  1. Habitual diet questionnaire

    Time frame: during 4 days before the MRI study

    subject will report food eaten at each meal

  2. MRI measured colon free water content

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

    MRI measured colon free water content, (in arbitrary units) after the drink test

  3. MRI measured small bowel and colon gas content

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

    small bowel and colon gas content (in arbitrary units) after the drink test

  4. MRI measured small bowel and colon volume

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

    small bowel and colon volume in arbritary units after drink test

  5. MRI measured oro-caecal transit time

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

    oro-caecal transit time (OCTT), (in arbitrary units) after the drink test

  6. Breath hydrogen and methane concentration measured in parts per million after drink test

    Time frame: baseline and then 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

  7. Symptoms of nausea, gas/flatulence, bloating and pain/discomfort measured using a Composite Symptom Score after the drink test

    Time frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

  8. Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by Comprehensive Nutrition Assessment Questionnaire

    Time frame: time 0

    CNAQ questionnaires results

  9. Hospital Anxiety and Depression Score

    Time frame: time 0

    scale measuring the score of anxiety and depression

  10. The Patient Health Questionnaire 12

    Time frame: Time 0

    Scale measuring the psychosomatic score

  11. Stool microbiota taxonomic

    Time frame: Up to 3 days before the MRI study

    Analysis of of microbiota taxonomic in the two stool samples collected by patient during the day before the MRI study day

  12. Stool microbiota alpha and beta diversity measurements

    Time frame: Up to three days before the MRI study day

    Analysis of alfa and beta diversity of microbiota in the two stool samples collected by patient before the study day

  13. Serum levels of short chain fatty acids

    Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

    Serum levels

  14. Circulating blood glucose levels

    Time frame: Baseline and then 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test

  15. Serum levels of surrogates of intestinal permeability (occludin, lipopolysaccharide binding protein)

    Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

    Serum levels

  16. Serum levels of lipidome and free fatty acids

    Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

    Serum levels

  17. Serum levels of total serum N-glycome and glucose

    Time frame: At baseline and 0, 60, 120, 180, 240, 300 minutes after the drink test

    Serum levels

  18. Food and drink avoidance questionnaire

    Time frame: at time 0

    patients will respond to the below questions:

    • Name of the food or drink you try to avoid.
    • Please tell us if you try to avoid this food or drink partially or completely? Approximately how long you have tried to avoid this food or drink partially or completely.

    Why do you try to avoid this food or drink partially or completely (including if you have been told to avoid it by a health care professional such as a doctor or dietitian)

  19. Leeds Food Preference Questionnaire

    Time frame: at time 0

    The LFPQ consists of two tasks requiring different interaction from the participant. One task requires an explicit evaluation of each food item using visual analogue scales. The other requires a quick choice to be made between paired combinations of foods. The order of task completion is randomised.

  20. Food Craving Questionnaire - State (FCQ-S)

    Time frame: at time 0

    participants respond to 14 questions about sugary food and they will respond with a scale from 1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree.

Study contacts

Contact information is provided by the study sponsor or research team.

Maura Corsetti, Medical Doctor

CONTACT

[email protected]

+447976448821

Sponsors and collaborators

Lead sponsor

University of Nottingham

Other

Collaborators

  • Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel
  • University of Veterinary Medicine Hannover
  • cic bioGune

Registry information

Official study 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)

Acronym: GenMalCarb2

Important dates

Study start
2025
Primary completion
2025
Study completion
2026
First posted
Jan 13, 2025
Registry last updated
Jan 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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