Tissue Destruction and Healing in Celiac Disease

Study Overview
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Brief Summary
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The purpose of this clinical study is to learn more about celiac disease pathogenesis and clinical symptoms. In particular, this study will examine the interactions between biological factors such as, intestinal epithelial cells, microbiota, immune system, genetics, and gluten and their effect on celiac disease clinical symptoms, and severity of tissue destruction and its ability to heal in individuals with celiac disease. Information collected in the study will help researchers to generate better resources to advance celiac disease patient care.

Detailed Description
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Celiac disease is an autoimmune enteropathy characterized by chronic inflammation of the small intestinal mucosa triggered by gluten uptake that occurs in genetically susceptible individuals carrying the specific class II human leucocyte antigens (HLA) DQ2 and DQ8 alleles. There is a spectrum in intestinal tissue damage associated with celiac disease. Some individuals develop inflammatory immunity in the absence of tissue damage, while others experience tissue damage ranging from partial to total villous atrophy. Persistent mucosal damage is associated with several severe complications, including lymphoproliferative malignancy and bone diseases. In addition, individuals with active celiac disease display a wide range of clinical symptoms, including metabolic defects that are not correlated to the degree of villous atrophy. Although much progress has been made in understanding celiac disease, major gaps remain in understanding biological mechanisms underlying inter-individual differences in clinical presentations and capacity to heal while maintaining a gluten-free diet.

Official Title
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Tissue Destruction and Healing in Celiac Disease

Conditions
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Celiac Disease

Intervention / Treatment
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* Dietary Supplement: Gluten containing snack bar


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gluten challenge group: Age 18 to 70 years old Diagnosis of Celiac disease for at least 12 months by intestinal biopsy Follow a strict gluten-free diet for at least the 12 consecutive months Gluten de-challenge group: Age 18 to 70 years old Showing typical celiac disease symptoms Not on a gluten-free diet Control group: Age 18 to 70 years old Females who are not pregnant Exclusion Criteria: Gluten challenge group: Diagnosis of any severe complication of celiac disease Diagnosis of other chronic, active GI disease Selective IgA deficiency Severe reaction to gluten exposure Any clinically significant diseases History of significant substance or alcohol abuse Pregnant or lactating Diagnosis of blood clotting disorders Gluten de-challenge group: History of chronic inflammatory gastrointestinal disease Gastrointestinal illness within the 4-week period prior to screening History of lymphoproliferative disease Uncontrolled blood clotting disorders Any clinically significant diseases History of significant substance or alcohol abuse Control group: Taking antibiotics, proton pump inhibitors, aspirin, or non-steroidal anti-inflammatory drugs Known intestinal inflammation Prior gastrointestinal surgery Taking of antiplatelet agents or anticoagulants Family history of celiac disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gluten challenge group<br>Diagnosis of celiac disease by intestinal biopsy and serology for at least 12 months | Dietary Supplement: Gluten containing snack bar<br>* Ingest snack bars containing 3 grams of gluten every day for 7 weeks.<br>|
| No Intervention: Gluten de-challenge group<br>Suspected celiac disease either showing typical symptoms or positive celiac disease serology | |
| No Intervention: Control group<br>No history or symptoms of celiac disease | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gluten challenge group: quantitative analysis of intestinal villus to crypt ratios | villus to crypt ratios will be quantified on small bowel biopsy samples for the histologic quantification of intestinal responses to disease processes. | baseline - 6 weeks | 
| Gluten de-challenge group: quantitative analysis of intestinal villus to crypt ratios | Villus to crypt ratios will be quantified on small bowel biopsy samples for the histologic quantification of intestinal responses to disease processes. | baseline -12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gluten-free diet, HLA-DQ2, HLA-DQ8, microbiome, metagenomics, intestinal epithelial cells