Changes in Intestinal Permeability 4 Hours After Gluten Challenge

Not Applicable

Completed

• Conditions: Wheat Hypersensitivity; Gluten Enteropathy; Duodenal Diseases; Celiac Disease; Gluten Sensitivity; Immune System and Related Disorders
• Interventions: Dietary Supplement: Gluten; Dietary Supplement: Placebo

• Registration Number: NCT03288831
• Lead Sponsor: Mayo Clinic

Brief Summary

This study evaluates why people with celiac disease and non-celiac gluten/wheat sensitivity develop rapid onset symptoms within hours of gluten exposure. Half of subjects will be given gluten and half will not.

Detailed Description

When a person with celiac disease is exposed to gluten, their immune system attacks their bowel and causes abdominal pain, bloating, and diarrhea. This process takes 24-72 hours to occur. Some people without celiac disease develop similar symptoms when they eat gluten or wheat. Doctors and scientists do not know what causes this sensitivity to gluten. People with celiac disease and non-celiac gluten sensitivity report symptoms within hours of being exposed to gluten. This study evaluates why this occurs by looking at changes in blood, urine, stool, and the bowel after being given gluten.

Study Timeline

• Study First Submitted: 2017-09-18
• Study First Submitted QC: 2017-09-18
• Study First Posted: 2017-09-20
• Study Start: 2017-10-10
• Primary Completion: 2018-10-30
• Study Completion: 2018-10-30
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-05
• Last Update Posted: 2019-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

• Tobacco use
• Symptomatic coronary disease
• Active, severe pulmonary disease
• Baseline oxygen requirement
• Coagulopathy (INR>1.5)
• Mastocytosis
• Active H. pylori infection
• Treated celiac disease with neutrophilia or eosinophilia secondary to infection
• Diabetes (type 1 and type 2)
• Crohn's disease or Ulcerative colitis
• Microscopic colitis
• Dermatitis herpetiformis
• Gastroparesis
• Pregnant women

Subjects exposed to the following medications during their respective time frames will be excluded:

• NSAIDs (24 hours)
• Leukotriene inhibitors (24 hours)
• Mast cell stabilizers (24 hours)
• Benzodiazepines (24 hours)
• H2 blockers (2 days)
• H1 blockers (7 days)
• Steroids (systemic or topically active within gastrointestinal tract) (30 days)
• Topical steroids (14 days)
• Intermittent (up to once weekly) tranquilizer (trazodone, doxepin) use (7 days)
• Chronic tricyclic antidepressant or tranquilizer use (trazodone, doxepin) Use of these medications will also be prohibited during the study duration (AAAAI and AAOA).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Celiac Subjects, Gluten Drink	Gluten	Subjects with celiac disease will drink a solution containing 6 grams of gluten one time.
Normal Subjects, Gluten Drink	Gluten	Normal subjects will drink a solution containing 6 grams of gluten one time.
Gluten Sensitivity, Placebo Drink	Placebo	Subjects with non-celiac gluten sensitivity will drink a solution without gluten one time.
Normal Subjects, Placebo Drink	Placebo	Normal subjects will drink a solution without gluten one time.
Celiac Subjects, Placebo Drink	Placebo	Subjects with celiac disease will drink a solution without gluten one time.
Gluten Sensitivity, Gluten Drink	Gluten	Subjects with non-celiac gluten sensitivity will drink a solution containing 6 grams of gluten one time.

Primary Outcome Measures

Name	Time	Method
Activation of the Mucosal Innate Immune System after Oral Gluten Challenge	4 hours	Small bowel biopsies will be assessed for markers of innate immune system activation: presence of granulocytes, granulocyte degranulation, products of degranulation, interleukins and cytokines involved in the innate immune system response, inflammatory mediators.

Secondary Outcome Measures

Name	Time	Method
Changes in Mucosal Permeability after Oral Gluten Challenge	Baseline and up to eight hours after gluten or placebo exposure	Mucosal permeability will be measure before and after oral gluten or placebo challenge with C13-mannitol lactulose urinary excretion testing. In addition, mucosal permeability will also be measured along the duodenum with a mucosal impedance probe.
Detection of Gluten Peptides in Urine and Stool	Baseline and up to 72 hours after gluten or placebo exposure	Urine and stool samples will be assessed for the presence of gluten peptides. This will help assess how long these tests are positive after a known gluten exposure.
Rapid Onset Symptom Development after Gluten Exposure	Baseline and up to 72 hours after gluten or placebo exposure	Subjects will record the symptoms they experience after gluten or placebo exposure. The will complete a simple symptom diary every 30 minutes for the first 2 hours.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States