Immunosafe-CeD: Are Partially Hydrolysed Gluten Hamrful to Celiac Disease Patients?

Study Overview
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Brief Summary
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The study will compare the immune response in CeD patients to wheat and barley gluten at high doses (1 gram), and also investigate the reponses to low dose barley gluten and also hydrolyzed, malted barley. This will be done by four one-day challenges with intervals around four weeks.

Detailed Description
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Celiac disease (CeD) is a common food-induced inflammatory disease of the small intestine caused by the ingestion of gluten from wheat, barley and rye. It is one of the most prevalent food hypersensitivities worldwide and affects 0.5-2.5% of the European population. The only effective treatment available is a strict lifelong gluten-free (GF) diet. GF products for CeD patients must not exceed the regulatory threshold of 20 mg/kg of gluten. Compliance of foods containing fermented or partially hydrolysed gluten is routinely assessed using the R5 competitive enzyme-linked immunosorbent assay (ELISA). However, this test does not adequately represent gluten immunogenicity in CeD patients. The overall objective of our ImmunoSafe-CeD proposal is to determine the CeD immunogenic activity of intact and partially hydrolysed gluten from wheat, rye and barley and develop improved comprehensive functional and analytical assays, including novel ELISAs and quantitative proteomics methods to ensure food safety for CeD patients. Thus, our objective is designed to directly address the needs of the CeD community about being reassured that GF products that contain partially hydrolysed gluten are safe and suitable for inclusion in their GF diet. By combining discovery proteomics and quantitative LC-MS/MS methods, improved reference materials for partially hydrolysed gluten, CeD-patient derived monoclonal antibodies and functional gluten-specific T-cell assays, we will provide a comprehensive and unique toolbox of novel and validated methods to detect gluten (both intact and partially hydrolysed) in foods for CeD patients. This toolbox will close the current discrepancy between food analytical methods and CeD immunogenicity for the first time, because all methods will be matched to clinical pathophysiology assessed by food challenge in CeD patients. Our multidisciplinary consortium is built on previous highly successful collaborations and we are well-positioned to create even more synergies between us by exchanging materials, know-how and data. We expect to 1) better understand the role that the different glutens play in CeD pathogenesis, 2) develop easy-to-perform and reliable analytical tools (ELISA) that quantitate and predict immunogenicity (toxicity) of wheat, rye and barley products for CeD patients, and 3) define foods that CeD patients can tolerate despite being partly based on these processed grains

Official Title
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Towards Comprehensive Analytical Methods for Partially Hydrolysed Gluten to Assess Product Safety for Celiac Disease Patients

Conditions
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Celiac Disease, Food Intolerance

Intervention / Treatment
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* Dietary Supplement: Wheat gluten 1000 mg
* Dietary Supplement: Barley gluten 1000 mg
* Dietary Supplement: Barley gluten 50 mg
* Dietary Supplement: Barley hydrolyzed gluten 50 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18 and 30 kg/m2 Biopsy verified celiac disease Pos gene test for HLA-DQ2.5 or DQ8 Strict glutenfree diet for at least 24 months Clinical remission Sensitive to gluten by accidental intake Effective contraception if female in fertile age Exclusion Criteria: Positive serology at screening Pregnant or lactating Other disease like Type 1 diabetes, cardiovascular disease, cancer, inflammatory bowel disease, thyroid or kidney disease On immunosuppressive drugs Smoking Food allergy including wheat allergy Acute infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will be challenged by single bolus four times four weeks apart.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Wheat gluten<br>In slurry, measurement of immune activation (Interleukin-2) four hours after intake | Dietary Supplement: Wheat gluten 1000 mg<br>* Nothing to add here<br>|
| Experimental: Barley gluten<br>In slurry, measurement of immune activation (Interleukin-2) four hours after intake | Dietary Supplement: Barley gluten 1000 mg<br>* Nothing to add here<br>|
| Experimental: Low dose barley gluten<br>In slurry, measurement of immune activation (Interleukin-2) four hours after intake | Dietary Supplement: Barley gluten 50 mg<br>* Nothing to add here<br>|
| Experimental: Low dose hydrolyzed barley gluten<br>In slurry, measurement of immune activation (Interleukin-2) four hours after intake | Dietary Supplement: Barley hydrolyzed gluten 50 mg<br>* Nothing to add here<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-2 in serum | Cytokine measurement by MSD Mesoscale | 4 hours after intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GIP in urine 4 hours after challenge and feces 2 days after challenge | Detection of gluten by test kits for BioMedal | Four hours after challenge (urine) and 2 days after challenge (feces) |