Tissue Destruction and Healing in Celiac Disease

Sponsor

University of Chicago (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05680012

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Mayo Clinic (Other), California Institute of Technology (Other)

220

Enrollment

Locations

Arms

53.9

Anticipated Duration (Months)

110

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Celiac Disease	Dietary Supplement: Gluten containing snack bar	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Tissue Destruction and Healing in Celiac Disease

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2027

Anticipated Study Completion Date :

Jun 30, 2027

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Gluten challenge group

Diagnosis of celiac disease by intestinal biopsy and serology for at least 12 months

Dietary Supplement: Gluten containing snack bar

Ingest snack bars containing 3 grams of gluten every day for 7 weeks.

No Intervention: Gluten de-challenge group

Suspected celiac disease either showing typical symptoms or positive celiac disease serology

No Intervention: Control group

No history or symptoms of celiac disease

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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