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

Официальное название

Genetic Carbohydrate Maldigestion As a Model to Study Food Hypersensitivity Mechanism and Guide Personalised Treatment Using a Non-invasive Multiparametric Test (WORK PACKAGE 2)

Обзор

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.

Вмешательства

• Другое Blood, stool and saliva collection
  Blood, stool and saliva collection
• Другое Questionnaire completion
  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
• Диагностический тест Magnetic Resonance Imaging (MRI) and Breath test
  MRI scans and breath test samples collected after drink test with sucrose

Первичные конечные точки

• Area under the curve [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]

Вторичные конечные точки (12)

• Habitual diet questionnaire [Срок оценки: during 4 days before the MRI study]
• MRI measured colon free water content [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• MRI measured small bowel and colon gas content [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• MRI measured small bowel and colon volume [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• MRI measured oro-caecal transit time [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• Breath hydrogen and methane concentration measured in parts per million after drink test [Срок оценки: baseline and then 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• Symptoms of nausea, gas/flatulence, bloating and pain/discomfort measured using a Composite Symptom Score after the drink test [Срок оценки: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes after the drink test]
• Total glucose and fructose and excess fructose, lactose, sorbitol, mannitol, oligosaccharides (Fructans and GOS) as measured by Comprehensive Nutrition Assessment Questionnaire [Срок оценки: time 0]
• Hospital Anxiety and Depression Score [Срок оценки: time 0]
• The Patient Health Questionnaire 12 [Срок оценки: Time 0]
• Stool microbiota taxonomic [Срок оценки: Up to 3 days before the MRI study]
• Stool microbiota alpha and beta diversity measurements [Срок оценки: Up to three days before the MRI study day]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Великобритания · 1 центр

• University of Nottingham — Nottingham

Идентификаторы

NCT: NCT06770907 · FMHS 215-0624

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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