Irritable Bowel Syndrome (IBS), Sucrase Isomaltase Deficiency
Conditions
Keywords
nutrigenetics, carbohydrates maldigestion
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.
Interventions
OTHERStool and saliva sample collection
Stool and saliva samples collection
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®
Sponsors
CICbioGUNE
Christian-Albrechts-University of Kiel
University of Veterinary Medicine Hannover
Nottingham University Hospitals NHS Trust
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
for Patients: * 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
Exclusion criteria
for Patients: * 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). Inclusion Criteria for healthy controls: * Between 5 and 70 years of age * Absence of Rome III IBS criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 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 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 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 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 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 |
| 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) |
Countries
United Kingdom
Outcome results
None listed