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

NCT06770907 | Not Yet Recruiting

• 1 other identifier: FMHS 215-0624
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sucrase Isomaltase Deficiency

Keywords

sucrose isomaltase deficiency

Outcome Measures

Primary Outcomes (1)

• Area under the curve

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

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

Secondary Outcomes (20)

• Habitual diet questionnaire

  during 4 days before the MRI study

• MRI measured colon free water content

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

• MRI measured small bowel and colon gas content

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

• MRI measured small bowel and colon volume

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

• MRI measured oro-caecal transit time

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

Study Arms (4)

Congenital Sucrase-Isomaltase Deficiency

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

Other: Blood, stool and saliva collection; Other: Questionnaire completion; Diagnostic Test: Magnetic Resonance Imaging (MRI) and Breath test

Healthy subjects

Subjects without CSID

Other: Blood, stool and saliva collection; Other: Questionnaire completion; Diagnostic Test: Magnetic Resonance Imaging (MRI) and Breath test

Asymptomatic controls single carriers

Subjects single carriers for sucrose isomaltase deficiency without symptoms

Other: Blood, stool and saliva collection; Other: Questionnaire completion; Diagnostic Test: Magnetic Resonance Imaging (MRI) and Breath test

Asymptomatic controls double carriers

Subjects double carriers for sucrose isomaltase deficiency without symptoms

Other: Blood, stool and saliva collection; Other: Questionnaire completion; Diagnostic Test: Magnetic Resonance Imaging (MRI) and Breath test

Interventions

Blood, stool and saliva collection OTHER

Blood, stool and saliva collection

Asymptomatic controls double carriers; Asymptomatic controls single carriers; Congenital Sucrase-Isomaltase Deficiency; Healthy subjects

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

Asymptomatic controls double carriers; Asymptomatic controls single carriers; Congenital Sucrase-Isomaltase Deficiency; Healthy subjects

Magnetic Resonance Imaging (MRI) and Breath test DIAGNOSTIC_TEST

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

Asymptomatic controls double carriers; Asymptomatic controls single carriers; Congenital Sucrase-Isomaltase Deficiency; Healthy subjects

Eligibility Criteria

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

Study Population

Single-centre study. CSID subjects will be identified and recruited either with the help of the PPI group through advertisements on social media or flyers at Clinical Genetics and Genomic Conferences and Adult Metabolic Disorder Conferences. Healthy participants will be recruited through social media advertisements and posters.

You may qualify if:

• 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.
• Ability to conform to the study protocol including the sucrose challenge.

You may not qualify if:

• 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.
• 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
• 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

Sponsors & Collaborators

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

Study Sites (1)

University of Nottingham

Nottingham, NG7 2UH, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

saliva, stools and blood samples.

MeSH Terms

Conditions

Sucrase-isomaltase deficiency, congenital

Interventions

Blood Specimen Collection; Defecation; Magnetic Resonance Imaging; Breath Tests

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Tomography; Diagnostic Imaging

Study Officials

• Maura Corsetti, Medical Doctor

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maura Corsetti, Medical Doctor

CONTACT

+447976448821; maura.corsetti@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Gastroenterology

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: January 13, 2025
• Study Start: March 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: March 1, 2026
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)