Irritable Bowel SyndromeRDS_CLENCT05056610
Confocal Laser Endomicroscopy to Determine Influence of Food Antigens on Mucosal Integrity
A study testing food antigens on duodenal mucosa in people with Irritable Bowel Syndrome and Food Sensitivity, run by University of Erlangen-Nürnberg Medical School at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome, Food Sensitivity, Healthy Controls
- What is being tested?
- food antigens on duodenal mucosa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteGermany
- Study dates
- 1 May 2021to 2 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- written informed consent
- patients with IBS who fulfil the criteria according to Rome IV
- patients with suspected IBS who undergo gastroduodenoscopy for diagnosis of IBS
- healthy controls with no suspicion of food intolerance and/or presented for screening with an indication for oesophago-gastrodudodenoscopy (e.g. medical preventive examination, exclusion of H. pylori or gastritis)
Who cannot join
- lack of written consent
- patients with known allergy to fluorescein.
- Patients with carcinoma, liver disease, proven bacterial overgrowth
- Patients with diabetes mellitus
- Patients with severe cardiovascular disease or multiple concomitant drug therapy (beta-blockers)
- Patients with wheat allergy
- Pregnant women
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Medicine 1, Hector Center for Nutrition, Exercise and Sports, Friedrich-Alexander-University Erlangen-Nuremberg
Erlangen, 91052
About this study
Official title: Bestimmung Des Einflusses Von Nahrungsmitteln Auf Die Darmschleimhaut Mit Der Konfokalen Laserendomikroskopie Und Humanen in Vitro Organoiden
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.
Read more
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.
Read the detailed 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.
- Conditions
- Irritable Bowel Syndrome, Food Sensitivity, Healthy Controls
- Being tested
- food antigens on duodenal mucosa
- Keywords
- confocal laser endomicroscopy, organoids, intestinal permeability
- Medical subject headings
- Irritable Bowel Syndrome, Food Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
food antigens on duodenal mucosaOther
Administration of food antigens on duodenal mucosa and determining the response through confocal laser endomicroscopy
| Study group | Role | What they receive |
|---|---|---|
| Patients with IBS or FI | Experimental | Food antigens are added to duodenal mucosa during CLE Receives: Other: food antigens on duodenal mucosa |
| healthy controls | Experimental | Food antigens are added to duodenal mucosa during CLE Receives: Other: food antigens on duodenal mucosa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of the intestinal barriere defects determined by CLE with histopathological data
Correlation of the histopathologically confirmed inflammation and mucosal damage with in vivo data evaluated by CLE. In vivo damage will be reported and evaluated by efflux of fluorescein into the gut lumen and endothel cell shedding.
Measured: 2 years
Determination of patients with IBS and response to food antigens
Determination of numbers of patients with IBS who show a response or change in permeability after application of the food antigens (wheat, soy, milk, yeast, chicken egg white) in CLE
Measured: 2 years
Secondary outcomes (2)
in vitro stimulation of intestinal organoids
RNA and protein analysis by RNA arrays, real-time PCR, Western blots, and enzyme linked immunoassays from organoids that are stimulated with food antigens.
Measured: 2 years
correlation of data between organoids and CLE
Correlation of data derived from in vitro organoids with in vivo assessment during CLE
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2021
- Study start1 May 2021
- Primary completion2 Jul 2024
- Study completion2 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by University of Erlangen-Nürnberg Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- During confocal endomicroscopy food antigens are given on the duodenal mucosa. The response of the mucosa is evaluated by the entry of fluorescein into the intestinal lumen and cell shedding
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, yurdagül zopf, University of Erlangen-Nürnberg Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05056610
- Sponsor's protocol ID
- Friedrich-Alexander-University
- Acronym
- RDS_CLE
- Status last verified
- Jul 2024
- First submitted
- 26 Jul 2021
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bestimmung Des Einflusses Von Nahrungsmitteln Auf Die Darmschleimhaut Mit Der Konfokalen Laserendomikroskopie Und Humanen in Vitro Organoiden
- ClinicalTrials.gov ID
- NCT05056610
- Acronym / sponsor ID
- RDS_CLE / Friedrich-Alexander-University
- Conditions
- Irritable Bowel Syndrome, Food Sensitivity, Healthy Controls
- Keywords
- confocal laser endomicroscopy, organoids, intestinal permeability
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Erlangen-Nürnberg Medical SchoolUniversity, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 2 Jul 2024 (actual)
- Study completion
- 2 Jul 2024 (actual)
- First posted
- 24 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- During confocal endomicroscopy food antigens are given on the duodenal mucosa. The response of the mucosa is evaluated by the entry of fluorescein into the intestinal lumen and cell shedding
| Arm | Type | Receives |
|---|---|---|
| Patients with IBS or FI | Experimental | Other: food antigens on duodenal mucosaFood antigens are added to duodenal mucosa during CLE |
| healthy controls | Experimental | Other: food antigens on duodenal mucosaFood antigens are added to duodenal mucosa during CLE |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- written informed consent
- patients with IBS who fulfil the criteria according to Rome IV
- patients with suspected IBS who undergo gastroduodenoscopy for diagnosis of IBS
- healthy controls with no suspicion of food intolerance and/or presented for screening with an indication for oesophago-gastrodudodenoscopy (e.g. medical preventive examination, exclusion of H. pylori or gastritis)
Key exclusion criteria (7 listed)
- lack of written consent
- patients with known allergy to fluorescein.
- Patients with carcinoma, liver disease, proven bacterial overgrowth
- Patients with diabetes mellitus
- Patients with severe cardiovascular disease or multiple concomitant drug therapy (beta-blockers)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| food antigens on duodenal mucosaAdministration of food antigens on duodenal mucosa and determining the response through confocal laser endomicroscopy | Other | Patients with IBS or FI, healthy controls |
Primary outcome
Correlation of the intestinal barriere defects determined by CLE with histopathological data
Time frame: 2 years
Correlation of the histopathologically confirmed inflammation and mucosal damage with in vivo data evaluated by CLE. In vivo damage will be reported and evaluated by efflux of fluorescein into the gut lumen and endothel cell shedding.
Determination of patients with IBS and response to food antigens
Time frame: 2 years
Determination of numbers of patients with IBS who show a response or change in permeability after application of the food antigens (wheat, soy, milk, yeast, chicken egg white) in CLE
2 secondary outcomes
in vitro stimulation of intestinal organoids
Time frame: 2 years
correlation of data between organoids and CLE
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing food antigens on duodenal mucosa in people with Irritable Bowel Syndrome and Food Sensitivity, run by University of Erlangen-Nürnberg Medical School at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of the intestinal barriere defects determined by CLE with histopathological data (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.