Eosinophilic EsophagitisPhase 1/2CLE-EoENCT05695456
Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy
A Phase 1/2 study testing personalized exclusion diet based on CLE and empiric exclusion diet in people with Eosinophilic Esophagitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Using confocal laser endomicroscopy (CLE), gastrointestinal allergic reactions to certain foods in the duodenum will be evaluated on a cellular level. After that, a personalized exclusion diet will be followed based on the CLE results for 6 weeks, sham-controlled, in a cross-over fashion. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Eosinophilic Esophagitis
- What is being tested?
- personalized exclusion diet based on CLE and empiric exclusion diet
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteBelgium
- Study dates
- 16 Feb 2022to Dec 2024
- Phase
- Phase 1/2
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
- Patients have had a trial of high-dose PPI for at least 8 weeks, with either documented non-response or intolerance to the medication
- Patients aged between 18 and 70 years old
- Signed written informed consent
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
- Patients have had a trial of high-dose PPI for at least 8 weeks, with either documented non-response or intolerance to the medication
- Patients aged between 18 and 70 years old
- Signed written informed consent
Who cannot join
- IgE-mediated food anaphylaxis for 1 of the trigger nutrients
- History of major gastrointestinal surgery complicating esophago-gastro-duodenoscopy
- Gastro-esophageal reflux disease (GERD) Los Angeles grade C or D
- Esophageal strictures, too narrow to pass with a normal gastroscope
- Endoscopic dilation in the esophagus in the 4 weeks prior to inclusion
- Celiac disease
Show all 11Show fewer
- Recent use (within two weeks) of non-steroidal anti-inflammatory drugs (NSAIDs), systemic histamine-receptor antagonists, mast cell stabilizers, opioids.
- Proton pump inhibitors must be either stopped for at least 4 weeks, or continued on a stable dosage throughout the study period.
- Corticosteroids should be stopped for at least 4 weeks.
- Allergy to fluorescein, Xylocain or Propofol
- Pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
Jan Tack
Leuven, Vlaams Brabant, 3000
Jan Tack, MD PhD, +3216345514, jan.tack@kuleuven.be
Karlien Raymenants, MD
About this study
Using confocal laser endomicroscopy (CLE), gastrointestinal allergic reactions to certain foods in the duodenum will be evaluated on a cellular level. After that, a personalized exclusion diet will be followed based on the CLE results for 6 weeks, sham-controlled, in a cross-over fashion. Gastroscopy with esophageal biopsies will be repeated after each diet.
Read the detailed description
Eosinophilic esophagitis is an antigen driven esophagitis, that is characterized by symptoms of dysphagia often leading to food impaction, and that leads to strictures and esophageal motility disorders, with a significant impact on quality of life. Current treatment options include proton pump inhibitors (PPI's) and topical steroids, and also the empiric 6-food elimination diet (6FED). In this diet, the 6 most frequently implicated foods are excluded and reintroduced one by one (milk, gluten containing grains, egg, soy, nuts, fish \& shellfish). However, this is a complicated and long process, including several endoscopies with esophageal biopsies.
Confocal laser endomicroscopy (CLE) is a technique that allows to detect gastrointestinal allergic reactions in the duodenum, and to visualize them on a molecular level in real-time. The CLE probe is passed through the working channel of a standard gastroscope, up against the duodenal mucosa. After intravenous injection of fluorescein as contrast medium, the duodenal epithelium is visualized on a cellular level, including food protein mediated extravasation of fluorescein into the lumen. The 6 foods of the 6FED are sprayed on the epithelium one by one, after which a reaction is awaited. Previous use of CLE has shown that more than half of Eosinophilic esophagitis (EoE) patients reacts to one or more foods during CLE.
In this double blind randomized cross-over study the effect a personalized elimination diet, based on the reaction during CLE, is compared to a sham diet, in patients with eosinophilic esophagitis, and insufficient response or intolerance to PPI's. Both diets will be followed for 6 weeks, after which gastroscopy with esophageal biopsies will be repeated. Patients that do not have a reaction to the 6 foods will act as controls, following a control diet with milk and gluten in a cross-over fashion.
- Conditions
- Eosinophilic Esophagitis
- Being tested
- personalized exclusion diet based on CLE, empiric exclusion diet
- Keywords
- confocal laser endomicroscopy, 6-food elimination diet, personalized exclusion diet
- Medical subject headings
- Eosinophilic Esophagitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
personalized exclusion diet based on CLEOther
personalized exclusion diet based on CLE
empiric exclusion dietOther
exclusion diet with milk or gluten-containing grains
| Study group | Role | What they receive |
|---|---|---|
| CLE positive patients real/sham | Active comparator | In this arm, participants who reacted to one or two nutrients during CLE will follow a personalized exclusion diet consistent of the nutrient to which they reacted, after which they will follow a sham diet in a blinded cross-over fashion. Receives: Other: personalized exclusion diet based on CLE |
| CLE positive patients sham/real | Sham comparator | In this arm, participants who reacted to one or two nutrients during CLE will follow a sham diet for 6 weeks, and than a personalized exclusion diet consistent of the nutrient to which they reacted, in a blinded cross-over fashion. Receives: Other: personalized exclusion diet based on CLE |
| CLE negative patients | Sham comparator | In this arm, participants who did not react to one of the nutrients during CLE will follow a control diet consistent of milk exclusion for 6 weeks, after which they will follow a gluten exclusion diet for 6 weeks, or the other way around. Receives: Other: empiric exclusion diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in response
Difference in response (defined as normalization of peak eosinophil count in esophageal mucosal biopsies <15 eosinophils/HPF) in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Measured: 2 years
Secondary outcomes (9)
Further histological outcomes
Difference in deep remission (defined as reduction of peak eosinophil count <6 eosinophils/HPF) before and after the targeted elimination diet respectively, compared with the sham diet
Measured: 2 years
Further histological outcomes
Difference in peak eosinophil count (eosinophils/HPF) before and after the targeted elimination diet, compared with the sham diet
Measured: 2 years
Symptomatic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
difference in symptoms using the DSQ (dysphagia symptom questionnaire), with a score from 0 (meaning no symptoms) to 10 (worse outcome).
Measured: 2 years
endoscopic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Difference in endoscopic reference score (EREFS) ranging from E0R0E0F0S0 (no endoscopic abnormalities) to E2R2E2F2S2 (worse endoscopic features)
Measured: 2 years
change in esophageal and duodenal permeability parameters 1
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
Measured: 2 years
change in esophageal and duodenal permeability parameters 2
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial flux of a high molecular weight protein is measured by labeling the molecule with a fluorescent dye.
Measured: 2 years
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Measured: 2 years
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 1
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
Measured: 2 years
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 2
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial flux of a high molecular weight protein is measured by labeling the molecule with a fluorescent dye.
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 posted25 Jan 2023
- Study start16 Feb 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Eosinophilic EsophagitisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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 1/2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A double-blind cross-over dietary elimination study: Patients with a positive CLE reaction to one or two specific nutrients will then be randomized to a blinded exclusion diet for 6 weeks of those nutrients or to exclusion of another tested nutrient that yielded no change in CLE (=sham diet), in a cross-over fashion. Patients with no CLE reaction will undergo an empirical exclusion diet of gluten-containing grains for 6 weeks. To mirror the crossover character of the intervention, CLE negative patients will then undergo a milk exclusion diet for 6 weeks (order is interchangeable).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05695456
- Sponsor's protocol ID
- S66223
- Acronym
- CLE-EoE
- Status last verified
- Mar 2024
- First submitted
- 15 Mar 2022
- Last updated
- 27 Jun 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy
- ClinicalTrials.gov ID
- NCT05695456
- Acronym / sponsor ID
- CLE-EoE / S66223
- Conditions
- Eosinophilic Esophagitis
- Keywords
- confocal laser endomicroscopy, 6-food elimination diet, personalized exclusion diet
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 16 Feb 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 25 Jan 2023 (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.
Using confocal laser endomicroscopy (CLE), gastrointestinal allergic reactions to certain foods in the duodenum will be evaluated on a cellular level. After that, a personalized exclusion diet will be followed based on the CLE results for 6 weeks, sham-controlled, in a cross-over fashion. Gastroscopy with esophageal biopsies will be repeated after each diet.
Detailed description
Eosinophilic esophagitis is an antigen driven esophagitis, that is characterized by symptoms of dysphagia often leading to food impaction, and that leads to strictures and esophageal motility disorders, with a significant impact on quality of life. Current treatment options include proton pump inhibitors (PPI's) and topical steroids, and also the empiric 6-food elimination diet (6FED). In this diet, the 6 most frequently implicated foods are excluded and reintroduced one by one (milk, gluten containing grains, egg, soy, nuts, fish \& shellfish). However, this is a complicated and long process, including several endoscopies with esophageal biopsies.
Confocal laser endomicroscopy (CLE) is a technique that allows to detect gastrointestinal allergic reactions in the duodenum, and to visualize them on a molecular level in real-time. The CLE probe is passed through the working channel of a standard gastroscope, up against the duodenal mucosa. After intravenous injection of fluorescein as contrast medium, the duodenal epithelium is visualized on a cellular level, including food protein mediated extravasation of fluorescein into the lumen. The 6 foods of the 6FED are sprayed on the epithelium one by one, after which a reaction is awaited. Previous use of CLE has shown that more than half of Eosinophilic esophagitis (EoE) patients reacts to one or more foods during CLE.
In this double blind randomized cross-over study the effect a personalized elimination diet, based on the reaction during CLE, is compared to a sham diet, in patients with eosinophilic esophagitis, and insufficient response or intolerance to PPI's. Both diets will be followed for 6 weeks, after which gastroscopy with esophageal biopsies will be repeated. Patients that do not have a reaction to the 6 foods will act as controls, following a control diet with milk and gluten in a cross-over fashion.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- A double-blind cross-over dietary elimination study: Patients with a positive CLE reaction to one or two specific nutrients will then be randomized to a blinded exclusion diet for 6 weeks of those nutrients or to exclusion of another tested nutrient that yielded no change in CLE (=sham diet), in a cross-over fashion. Patients with no CLE reaction will undergo an empirical exclusion diet of gluten-containing grains for 6 weeks. To mirror the crossover character of the intervention, CLE negative patients will then undergo a milk exclusion diet for 6 weeks (order is interchangeable).
| Arm | Type | Receives |
|---|---|---|
| CLE positive patients real/sham | Active comparator | Other: personalized exclusion diet based on CLEIn this arm, participants who reacted to one or two nutrients during CLE will follow a personalized exclusion diet consistent of the nutrient to which they reacted, after which they will follow a sham diet in a blinded cross-over fashion. |
| CLE positive patients sham/real | Sham comparator | Other: personalized exclusion diet based on CLEIn this arm, participants who reacted to one or two nutrients during CLE will follow a sham diet for 6 weeks, and than a personalized exclusion diet consistent of the nutrient to which they reacted, in a blinded cross-over fashion. |
| CLE negative patients | Sham comparator | Other: empiric exclusion dietIn this arm, participants who did not react to one of the nutrients during CLE will follow a control diet consistent of milk exclusion for 6 weeks, after which they will follow a gluten exclusion diet for 6 weeks, or the other way around. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
- Patients have had a trial of high-dose PPI for at least 8 weeks, with either documented non-response or intolerance to the medication
- Patients aged between 18 and 70 years old
- Signed written informed consent
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
Key exclusion criteria (11 listed)
- IgE-mediated food anaphylaxis for 1 of the trigger nutrients
- History of major gastrointestinal surgery complicating esophago-gastro-duodenoscopy
- Gastro-esophageal reflux disease (GERD) Los Angeles grade C or D
- Esophageal strictures, too narrow to pass with a normal gastroscope
- Endoscopic dilation in the esophagus in the 4 weeks prior to inclusion
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 |
|---|---|---|
| personalized exclusion diet based on CLEpersonalized exclusion diet based on CLE | Other | CLE positive patients real/sham, CLE positive patients sham/real |
| empiric exclusion dietexclusion diet with milk or gluten-containing grains | Other | CLE negative patients |
Primary outcome
Difference in response
Time frame: 2 years
Difference in response (defined as normalization of peak eosinophil count in esophageal mucosal biopsies <15 eosinophils/HPF) in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
9 secondary outcomes
Further histological outcomes
Time frame: 2 years
Further histological outcomes
Time frame: 2 years
Symptomatic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Time frame: 2 years
endoscopic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Time frame: 2 years
change in esophageal and duodenal permeability parameters 1
Time frame: 2 years
change in esophageal and duodenal permeability parameters 2
Time frame: 2 years
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Time frame: 2 years
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 1
Time frame: 2 years
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 2
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2024.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing personalized exclusion diet based on CLE and empiric exclusion diet in people with Eosinophilic Esophagitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 8 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 27 Jun 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 Belgium. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jan Tack, MD PhD (+3216345514, jan.tack@kuleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in response (time frame: 2 years). 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 27 Jun 2024.