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Completed

NCT Number: NCT03288831

Changes in Intestinal Permeability 4 Hours After Gluten Challenge

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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for subjects with Celiac Disease:

  • Biopsy proven celiac disease diagnosed at least 2 years prior to recruitment
  • Attest to following a gluten free diet to the best of their ability
  • Quiescent symptoms on a gluten free diet
  • Negative tissue transglutaminase at time of recruitment (to be collected with baseline blood work)
  • A prior endoscopy with small bowel biopsies reviewed by a gastrointestinal pathologist revealing healing

Inclusion criteria

for subjects with Non-Celiac Gluten Sensitivity:

  • Meet diagnostic consensus criteria as defined by Ludvigsson et al in "The Oslo definitions for coeliac disease and related terms"
  • Attest to following a gluten free diet to the best of their ability
  • Quiescent symptoms on a gluten free diet
  • Prior negative evaluation for celiac disease (including tissue transglutaminase IgA with total IgA or small bowel biopsies)
  • If subjects have had a small bowel biopsies revealing increased intraepithelial lymphocytes (IELs), they will be reviewed as a separate subgroup

Inclusion criteria

for Normal Subjects:

  • No gastrointestinal diagnosis (reflux, eosinophilic esophagitis, inflammatory bowel disease, or irritable bowel syndrome)
  • No gastrointestinal symptoms (diarrhea, abdominal pain, nausea, vomiting, weight loss)
  • No family history of celiac disease
  • Will not be required to have a baseline biopsy

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).

Treatment and study plan

gluten

Dietary Supplement

Six grams of gluten will be mixed with water and Tang flavoring. Subjects will drink the mixture one time.

Placebo

Dietary Supplement

Subjects will drink a mixture of rice water and Tang flavoring one time.

Primary outcomes

  1. Activation of the Mucosal Innate Immune System after Oral Gluten Challenge

    Time frame: 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 outcomes

  1. Changes in Mucosal Permeability after Oral Gluten Challenge

    Time frame: 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.

  2. Detection of Gluten Peptides in Urine and Stool

    Time frame: 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.

  3. Rapid Onset Symptom Development after Gluten Exposure

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Registry information

Official study title

The Innate Response to and Changes in Intestinal Permeability 4 Hours After a Gluten Challenge in Subjects With Celiac Disease and Non Celiac Gluten Sensitivity

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Sep 20, 2017
Registry last updated
Jun 7, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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