Diagnostic Performance of Urinary Gluten Immunogenic Peptides in Monitoring the Adherence to Gluten-free Diet.

Study Overview
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Brief Summary
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The purpose of the GRRES study is to assess the clinical usefulness of urinary gluten immunogenic peptides test as a marker of gluten-free diet adherence using the rapid immunochromatographic assay based on anti-gliadin 33-mer monoclonal antibodies.

Detailed Description
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A strict and permanent gluten free diet (GFD) is the only effective treatment resulting in full clinical, serological and histological remission, avoiding long-term complications in celiac disease (CD) patients. Gluten immunogenic peptides (GIP) are fragments of gluten proteins resistant to gastrointestinal digestion and detectable in urine after intestinal digestion, providing direct evidence of recent gluten ingestion. A significant variability in the amount of excreted urinary GIP has been reported in individuals administered with similar doses of gluten and, so far, inadequate information is available about the amount of excreted GIP in subjects ingesting traces or low amount of gluten. This is an important issue, as even a strict GFD could be contaminated by traces of gluten, e.g. in wheat starch and processed food. The aim of this study is to assess the clinical usefulness of urinary GIP as a marker of GFD adherence using a rapid immunochromatographic assay based on anti-gliadin 33-mer monoclonal antibodies. This is a prospective, randomized, triple-blind, placebo-controlled, clinical trial. In this study, healthy volunteers following a normal diet will be requested to be on strict GFD for 5 days. On day 4th, participants will be requested to collect a baseline urine sample and in case of a negative GIP test result they will be assigned to ingest a specific dose of purified gluten incorporated in a capsule (0 mg, 10 mg, 50 mg, 100 mg, 500 mg and 1000 mg, according to randomization). Participants will be requested to collect urine samples in a container and take a 5 mL aliquote for the GIP test at the 9th and 24th hour from the time of the administration of the dose. During the collection, volunteers will also be requested to record the volume of the excreted urine and to store the collected urine at 4°C. Urine tubes will be stored at -20°C until the quantitative evaluation of GIP. GIP test will be performed using the rapid immunochromatographic assay based on anti-gliadin 33-mer monoclonal antibodies iVYCHECK GIP Urine™ test (Biomedal, Spain) according to the manufacturer's instructions.

Official Title
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A Randomized, Triple-blind, Placebo-controlled, Clinical Trial on the Diagnostic Performance of Gluten Immunogenic Peptides in the Evaluation of Gluten-free Diet Adherence: the GRRES Study.

Conditions
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Celiac Disease

Intervention / Treatment
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* Behavioral: Gluten (behaviour)
* Behavioral: Placebo (behaviour)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy volunteers 20-40 years old written informed consent Exclusion Criteria: type 1 diabetes chronic or acute inflammatory diseases of the gastrointestinal tract (CD, non-celiac gluten sensitivity, Crohn's disease, ulcerative colitis, food allergy, acute gastroenteritis ≤ 4 weeks prior to the study start) pregnancy or lactation chronic intake of medications and supplements refusal/withdrawal of written informed consent.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Oral administration of one capsule of Placebo | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|
| Active Comparator: Purified gluten (10 mg)<br>Oral administration of capsules containing 10 mg of purified gluten. | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|
| Active Comparator: Purified gluten (50 mg)<br>Oral administration of capsules containing 50 mg of purified gluten. | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|
| Active Comparator: Purified gluten (100 mg)<br>Oral administration of capsules containing 100 mg of purified gluten. | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|
| Active Comparator: Purified gluten (500 mg)<br>Oral administration of capsules containing 500 mg of purified gluten. | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|
| Active Comparator: Purified gluten (1000 mg)<br>Oral administration of capsules containing 1000 mg of purified gluten. | Behavioral: Gluten (behaviour)<br>* Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).<br>Behavioral: Placebo (behaviour)<br>* Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-response relationship between the amount of gluten intake and urinary excretion of GIP. | The primary objective of the study is to verify the usefulness of the quantitative GIP assay in urine as biomarker of adherence to the gluten-free diet in terms of dose-response relationship between the amount of ingested gluten and urinary excretion of GIP in a group of healthy volunteers. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gluten-free diet, Gluten immunogenic peptides, Gluten contamination, Gluten, Urine