Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05056610 |
| Other study ID # |
Friedrich-Alexander-University |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2021 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
January 2023 |
| Source |
University of Erlangen-Nürnberg Medical School |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Irritable bowel syndrome (IBS) is mainly associated with food intolerance and presents a
particular challenge in gastrointestinal practice. The clinical symptoms are often associated
by patients with the consumption of certain foods. This leads to strict elimination diets,
and often without identification of the triggering food. In particular, the avoidance of
wheat yields a relief of the clinical symptoms in many patients. Nevertheless, it is unclear
which components of wheat are responsible for the symptoms. Besides the glutens, other wheat
proteins, such as the amylase trypsin inhibitors, but also carbohydrates are discussed as
triggers of the diseases.
Confocal laser endomicroscopy (CLE) is a new diagnostic method for detecting the local effect
of food on the mucosa. CLE enables microscopic assessment of the mucosa already during an
endoscopic examination and also allows statements to be made about intestinal permeability
through changes in the influx of fluorescein into the intestinal lumen. In the course of the
study, diluted food solutions are applied to the mucosa after a detailed assessment of the
mucosa via the endoscope. The changes in mucosa and permeability are observed and documented.
Tissue samples are then taken for histopathological assessment of the degree of inflammation.
Further biopsies are taken and cultured in vitro to produce human organoids. The organoids
are stimulated with the food. Changes in proliferation, gene and cytokine expression are
determined.
The aim of the proposed project is to investigate the influence of the main allergens, e.g.
wheat, soy, milk, yeast and chicken egg white on the intestinal mucosa. The data obtained
will be compared with the histopathological findings and the in vitro data in the human
organoid model.
The long-term goal is to establish a valid patient-based rapid detection method for the
detection of the triggering substances in patients with IBS or food intolerances.
Description:
Patients with IBS of unclear etiology, i.e. non-IgE mediated food intolerances (FI), often
have a long course of suffering. It is not uncommon for patients to follow self-imposed
strict diets to alleviate food-dependent intestinal and extraintestinal symptoms. However,
these diets carry a high risk of malnutrition. In practice, an elimination diet followed by
provocation of individual foods attempts to identify the triggers of the intolerances.
However, since the reaction to the food antigens can occur with a delay and not infrequently
a combination of several intolerances is present, the correct diagnosis is often difficult.
This often leads to a massively reduced quality of life for the patients and repeated
examinations, such as gastrointestinal endoscopies, which lead to the patient being
hospitalised again.
In addition to medical approaches to alleviate the symptoms (drugs for diarrhoea, laxatives
for constipation), an improvement is often achieved through a change in diet. Recently, there
have been increasing reports that patients with IBS respond to a diet that is reduced in
FODMAPs (fermentable oligo-, di- and monosaccharides as well as polyols) with a significant
improvement in symptoms. Furthermore, patients with IBS often report significant symptom
relief with adherence to a gluten-free diet (GFD), so that current estimates suggest that
almost half of patients with IBS benefit from a GFD.
The introduction of CLE provides a new objective method for detecting changes at the cellular
level.The CLE allows a microscopic assessment of the mucosa already during the endoscopic
examination and thus enables an vivo histology, with an exact analysis of the intestinal
mucosa.
Others already showed that stimulation of intestinal mucosa with food antigens causes an
increased permeability and cell shedding in patients with FI (Fritscher-Ravens et al.
Gastroenterology 2014). The response to food antigens can be visualized after administration
of intravenous fluorescein and measurement of the release of fluroescein in the gut lumen. A
major advantage of CLE is the direct local assessment of food antigens on the intestinal
mucosa and the identification of patients who have a clinically relevant FI.
Hypothesis: We suggest that patients with IBS and/or FI react more strongly to mucosal
applied food antigens than healthy controls due to an existing low-grade intestinal
inflammation. We plan to apply wheat, soy, milk, yeast and chicken egg white during CLE and
record cell shedding and fluorescein efflux in the gut lumen. Since many patients with IBS
are known to respond positively to a wheat-free diet, we expect the strongest mucosal
response especially after application of wheat.
The aim is to prove our hypothesis by the increased cell shedding and the increased efflux of
fluorescein into the intestinal lumen.
After CLE, tissue samples are taken for routine histopathological analysis. In addition,
mucosal biopsies are taken and used to isolate stem cells and generate in vitro organoids.
These organoids are cultured and supplemented with food antigens and changes in
proliferation, gene, cytokine and chemokine expression are determined.
The primary goal is
- the evaluation of CLE with histopathological data, this means the determination of
patients who have a good match of histopathologically confirmed inflammation with the
assessment of mucosal changes detrrmined in CLE
- to determine the number of patients with IBS who have an response or change in
permeability after application of the food antigens (wheat, soy, milk, yeast, chicken
egg white) in CLE
Secondary objectives are
- the identification of molecular parameters after stimulation of in vitro organoids with
food antigens
- the correlation of data derived from in vitro organoids with in vivo assessment during
CLE
The study is planned for a period of 2 years. 40 patients aged 18 years and older with IBS
who have a clinical need for oesophago-gastroduodenoscopy, e.g. to diagnose IBS or to exclude
inflammatory bowel disease, gastritis, eosinophilic oesophagitis or coeliac disease, will be
included in the study. Furthermore, 20 healthy control subjects who come for preventive
medical checkup will be included.
Food antigens are applied during oesophago-gastroduodenoscopy, starting in the distal
duodenum and proceeding sequentially to the proximal duodenum. The application of food
antigens is randomised. The biopsies are taken after the application of the food antigens
from the duodenal mucosa and used for histopathological analysis or in vitro generation of
organoids.
