Clinical trial NCT06151782: Immunosafe-CeD: Are Partially Hydrolysed Gluten Hamrful to Celiac Disease Patients?
Official title: Towards Comprehensive Analytical Methods for Partially Hydrolysed Gluten to Assess Product Safety for Celiac Disease Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Celiac Disease
Food Intolerance
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2023-11-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be challenged by single bolus four times four weeks apart.
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Interleukin-2 in serum
timeFrame: 4 hours after intake
Secondary outcomes:
measure: GIP in urine 4 hours after challenge and feces 2 days after challenge
timeFrame: Four hours after challenge (urine) and 2 days after challenge (feces)
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Clinical Center for Celiac Disease and Autoimmunity
city: Oslo
country: Norway
facility: Dept of Gastroenterology
Study officials:
affiliation: Oslo University Hospital
name: Knut E A Lundin, PPhD, MD
role: PRINCIPAL_INVESTIGATOR
References: