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

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

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 and placebo. This will be done by five one-day challenges with intervals around four weeks.

Study Overview

• Status: Completed
• Conditions: Celiac Disease; Food Intolerance
• Intervention / Treatment: 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; Dietary supplement: Placebo slurry

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

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Germany
    • Mainz, Germany, Germany, 55131
      • Clinical Center for Celiac Disease and Autoimmunity
• Norway
  • Oslo
    • Oslo, Oslo, Norway, 0881
      • Dept of Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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)
Immune reaction to wheat and barley	Whole-blood cytokine release assay where blood is challenged with gluten peptides	Before each patient has been challenged
PROM	Gastrointestinal symptom score after challenge assessed scoring forms	At baseline and at each of the five challenges; at time 0, 1hour, 2hours, 3hours and 4hours after the challenge. We use a VAS score and the GSRS form.

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Knut E A Lundin, PPhD, MD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): June 1, 2025

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 28, 2023
• First Posted (Actual): November 30, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Signs and Symptoms, Digestive; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Malabsorption Syndromes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Food Intolerance; Celiac Disease; Amino Acids, Peptides, and Proteins; Proteins; Plant Proteins; Prolamins; Grain Proteins; Seed Storage Proteins; Glutens
• Other Study ID Numbers: 2637128

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No