Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05159115 |
| Other study ID # |
MED 358 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 14, 2022 |
| Est. completion date |
December 31, 2027 |
Study information
| Verified date |
November 2021 |
| Source |
Lovisenberg Diakonale Hospital |
| Contact |
Jørgen Valeur, PhD |
| Phone |
0047 23225140 |
| Email |
jorgen.valeur[@]lds.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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:
1. 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
2. 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
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.
