Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity (GenMalCarb)

August 11, 2023 updated by: Nottingham University Hospitals NHS Trust

Genetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity Mechanism and Guide Personalised Treatment Using a Non-invasive Multiparametric Test (Work Package 1)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

2000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Multicentre study. IBS patients identified through secondary and tertiary care gastroenterological clinics.

Asymptomatic adult controls recruited at the same site as respective patients or, for instance, from transfusion clinics, blood donor centres, bowel cancer screening as long as data on the absence of symptoms is documented.

Description

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

Exclusion Criteria for healthy controls:

  • Blood relatives of the participating IBS patient are not allowed to participate.
  • Person with any condition which, in the opinion of the investigator, makes them unsuitable for participation in the study.
  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
IBS Patient
IBS patient with diarrhoea or alternating bowel habit
Other: Stool and saliva sample collection
Stool and saliva samples collection
Other: Questionnaire completion

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®
Healthy subject
Participants without IBS
Other: Stool and saliva sample collection
Stool and saliva samples collection
Other: Questionnaire completion

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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of IBS-D and IBS-M with of SI and CDG hypomorphic variants as compared to asymptomatic controls
Time Frame: baseline
the prevalence of SI and CDG hypomorphic variants in IBS-D and IBS-M patients across countries and ethnicities, compared to asymptomatic controls
baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in age between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: baseline

Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene:

- age in years
baseline
Difference in gender between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: baseline

Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene:

- gender
baseline
Difference in ethnicity between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: baseline

Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene:

- ethnicity
baseline
Difference in IBS subtype between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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)
baseline
Difference in post-infectious onset between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: baseline

Evaluate whether the below parameters differs between patients carriers and non-carriers of defective (hypomorphic) gene:

- number of patients with post-infectious onset
baseline
Difference in number of previous abdominal surgery between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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
baseline
Difference in symptoms presentations between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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.
baseline
Difference in anxiety and depression between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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)
baseline
Difference in somatisation between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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.
baseline
Difference in habitual intake of sugars between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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
baseline
Difference in quality of life between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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
baseline
Difference in symptoms between patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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
baseline
Difference in anxiety and depression between paediatric patients carriers and non-carriers of defective (hypomorphic) gene
Time Frame: 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.
baseline
Difference in in vitro SI enzyme activity in human cells with defective gene as compare with those with normal gene
Time Frame: 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
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nottingham University Hospitals NHS Trust

Collaborators

CICbioGUNE
Christian-Albrechts-University of Kiel
University of Veterinary Medicine Hannover

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2023

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

January 23, 2023

First Submitted That Met QC Criteria

March 29, 2023

First Posted (Actual)

April 3, 2023

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 11, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20GA093
  • 288003 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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