Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome
Primary Purpose
Irritable Bowel Syndrome, Sucrose Intolerance Due to Sucrase-Isomaltase Deficiency, Carbohydrate; Malabsorption
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Low-FODMAP diet
Starch- and Sucrose Reduced Diet (SSRD)
Sponsored by
About this trial
This is an interventional treatment trial for Irritable Bowel Syndrome
Eligibility Criteria
Validation of the 13C-labelled breath test to diagnose sucrase-isomaltase deficiency (n=40)
Inclusion Criteria:
- Signed informed consent
- BMI 18-30 kg/m2
- Referred for gastroscopic examination with suspected GI disorder
Exclusion Criteria:
• Unwilling or not capable of signing the informed consent
Sucrase-isomaltase deficiency as a cause of symptoms in patients with irritable bowel syndrome (n=80)
Inclusion Criteria:
- Signed informed consent
- BMI 18-30 kg/m2
- IBS diagnosis according to Rome IV criteria
Exclusion Criteria:
- Inflammatory bowel disease, celiac disease or diabetes mellitus
- Chronic immune diseases affecting the GI-system
- Unwilling/unable to maintain a stable diet throughout the study period
- Use of antibiotic treatment for the last 4 weeks
- Currently on a restrictive diet
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Low-FODMAP diet
Starch- and Sucrose Reduced Diet
Arm Description
Patients with IBS on a 4-week low-FODMAP diet.
Patients with IBS on a s 4-week Starch- and Sucrose Reduced Diet (SSRD).
Outcomes
Primary Outcome Measures
IBS symptom severity
Symptom severity measured by the IBS-Symptom Severity Scale (IBS-SSS)
Secondary Outcome Measures
Gut microbiota composition
Analysis of fecal samples for evaluation of microbiota composition in fecal samples collected at baseline and after each 4-week diet intervention
Fecal fermentation measured by short chain fatty acids (SCFAs)
Analysis of SCFAs in fecal samples collected at baseline and after each 4-week diet intervention
Quality of life in IBS
Assessment of quality of life by the Patient Reported Outcome Measurement Information System (PROMIS-29)
Full Information
NCT ID
NCT05159115
First Posted
December 6, 2021
Last Updated
January 18, 2022
Sponsor
Lovisenberg Diakonale Hospital
Collaborators
University of Bergen
1. Study Identification
Unique Protocol Identification Number
NCT05159115
Brief Title
Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome
Official Title
Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 14, 2022 (Anticipated)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lovisenberg Diakonale Hospital
Collaborators
University of Bergen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Irritable bowel syndrome (IBS) is a functional disorder causing troublesome symptoms and reduced quality of life. It affects 10-20% of the population, hence creates large costs for society. About 30-40% of all IBS patients do not benefit from current treatment options. Sucrase-isomaltase (SI) deficiency is an unexplored condition, that may explain symptoms in IBS patients who experience no effect from today's treatments. Currently, a duodenal biopsy is the gold standard for the diagnosis of SI deficiency, however the condition is not well investigated. A 13C-labelled breath test holds promise as a non-invasive alternative, but it has not previously been validated.
This project will address the knowledge gap related to a possible association between SI deficiency and IBS by addressing two research questions that have never been answered before. We aim to:
Validate the 13C-labelled breath test as a diagnostic tool by assessing the strength of the association between the breath test and SI activity measured in duodenal biopsies
Use the 13C-labelled breath test in a randomized dietary crossover trial comparing a starch and sucrose reduced diet (SSRD) with the standard low-FODMAP diet in IBS patients, to evaluate whether SI activity is associated with dietary changes according to symptom severity and gut microbiota composition
Detailed Description
The projects includes two studies:
Study 1: Validation of the 13C-labelled breath test to diagnose sucrase-isomaltase deficiency
Background: In order to validate the 13C-sucrose breath test to diagnose SI deficiency, the test result must be compared to the "gold standard" method for diagnosis; i.e. measurements of enzyme activity from intestinal biopsies by "The Dahlquist Method", and a reference material must be established.
Objective: To compare results from the 13C-labelled breath test to enzyme activity measured in biopsies collected from the proximal small intestine in a limited patient group referred for a gastroscopic examination.
Design: A cross-sectional study.
Primary endpoint: SI activity as measured with a breath test and enzyme activity with assay of biopsy material.
Recruitment and patient characteristics: Patients referred for gastroscopic examination with duodenal biopsies and with suspected GI disorder, will be included consecutively.
Sample size: We aim to include 40 patients. No studies validating breath test results in our patient group are available. However, based on preliminary results suggesting that 35% of IBS patients have SI deficiency,13 we are 95% likely to find between 8 and 21 patients with SI deficiency when examining 40 patients. Assuming 80% concordance between the two methods to (correct proportion of successes), we would need 12 positive cases. Thus, if 40 individuals are included, the study is sufficiently powered (alpha=5% and beta=20%, using McNemar's test of concordance).
Study 2: Sucrase-isomaltase deficiency as a cause of symptoms in patients with irritable bowel syndrome
Objectives: To examine the effect of a 4-week SSRD on GI- and extraintestinal symptoms, gut microbiota composition and fecal fermentation in patients with IBS (with and without SI deficiency), and compare the SSRD with a 4-week low-FODMAP diet to investigate whether the patients with a breath test result indicating SI deficiency respond better to the SSRD than the patients with normal SI activity. Gut microbiota have been suggested to have a central role in IBS etiology, hence evaluation of gut microbiota composition and fecal fermentation will be included to increase the knowledge regarding the effects of dietary change on gut microbiota composition and activity related to SI deficiency.
Design: A randomized, open clinical crossover trial with a dietary intervention in a group of IBS patients, lasting for 4+4 weeks (SSRD vs. low-FODMAP) with a 1-week wash-out period in between. Breath tests will be taken at inclusion, but the results will be "blinded", e.g. not available for anyone conducting the trial before end of the study. A SSRD will be compared to the low-FODMAP diet. All participants will be given dietary advice from a registered clinical dietitian. Briefly, all forms of sucrose-containing foods (e.g. sweets, jam, and cakes) should be avoided, and foods rich in starch should be reduced on the SSRD.
Primary endpoint: Symptom severity by IBS-Symptom Severity Scale (IBS-SSS).
Secondary endpoints: Gut microbiota composition, fecal fermentation measured by short chain fatty acids (SCFAs) and assessment of quality of life by the Patient Reported Outcome Measurement Information System (PROMIS-29).
Recruitment and patient characteristics: IBS patients referred to the outpatient clinic at the Department of Gastroenterology at Lovisenberg Diaconal Hospital for dietary guidance by a registered dietitian will be consecutively included.
Sample size: The primary end point is change in IBS symptom severity (IBS-SSS) at the end of the treatment period relative to baseline, and the proportion of responders to the dietary intervention is based on the recommended cut-off of a reduction (ie, improvement) in total IBS-SSS score of 50 points, which is considered to be clinically meaningful improvement. To plan our sample size, we performed a power calculation based on the ability to detect a difference between the two diets in reduction of IBS-SSS score of at least 50 points with 80% power, assuming an SD of 100. The calculation indicated that we would need 64 patients. To allow for 15-20% drop-out, we aim to include 80 patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome, Sucrose Intolerance Due to Sucrase-Isomaltase Deficiency, Carbohydrate; Malabsorption, Sucrase Isomaltase Deficiency, Functional Gastrointestinal Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Low-FODMAP diet
Arm Type
Active Comparator
Arm Description
Patients with IBS on a 4-week low-FODMAP diet.
Arm Title
Starch- and Sucrose Reduced Diet
Arm Type
Experimental
Arm Description
Patients with IBS on a s 4-week Starch- and Sucrose Reduced Diet (SSRD).
Intervention Type
Other
Intervention Name(s)
Low-FODMAP diet
Intervention Description
4 weeks of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs)
Intervention Type
Other
Intervention Name(s)
Starch- and Sucrose Reduced Diet (SSRD)
Intervention Description
4 weeks of a diet low in starch and sucrose
Primary Outcome Measure Information:
Title
IBS symptom severity
Description
Symptom severity measured by the IBS-Symptom Severity Scale (IBS-SSS)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Gut microbiota composition
Description
Analysis of fecal samples for evaluation of microbiota composition in fecal samples collected at baseline and after each 4-week diet intervention
Time Frame
4 weeks
Title
Fecal fermentation measured by short chain fatty acids (SCFAs)
Description
Analysis of SCFAs in fecal samples collected at baseline and after each 4-week diet intervention
Time Frame
4 weeks
Title
Quality of life in IBS
Description
Assessment of quality of life by the Patient Reported Outcome Measurement Information System (PROMIS-29)
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Validation of the 13C-labelled breath test to diagnose sucrase-isomaltase deficiency (n=40)
Inclusion Criteria:
Signed informed consent
BMI 18-30 kg/m2
Referred for gastroscopic examination with suspected GI disorder
Exclusion Criteria:
• Unwilling or not capable of signing the informed consent
Sucrase-isomaltase deficiency as a cause of symptoms in patients with irritable bowel syndrome (n=80)
Inclusion Criteria:
Signed informed consent
BMI 18-30 kg/m2
IBS diagnosis according to Rome IV criteria
Exclusion Criteria:
Inflammatory bowel disease, celiac disease or diabetes mellitus
Chronic immune diseases affecting the GI-system
Unwilling/unable to maintain a stable diet throughout the study period
Use of antibiotic treatment for the last 4 weeks
Currently on a restrictive diet
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jørgen Valeur, PhD
Phone
0047 23225140
Email
jorgen.valeur@lds.no
12. IPD Sharing Statement
Plan to Share IPD
No
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Sucrase-isomaltase Deficiency as a Cause of Irritable Bowel Syndrome
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