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Changes in Intestinal Permeability 4 Hours After Gluten Challenge

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ClinicalTrials.gov Identifier: NCT03288831
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : November 22, 2017
Sponsor:
Information provided by (Responsible Party):
Joseph A. Murray, M.D., 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.

Condition or disease Intervention/treatment Phase
Celiac Disease Wheat Hypersensitivity Gluten Sensitivity Gluten Enteropathy Immune System and Related Disorders Duodenal Diseases Dietary Supplement: Gluten Dietary Supplement: Placebo Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blinded, placebo-controlled oral gluten challenge
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Subjects will be block randomized to either gluten-containing or placebo challenge.
Primary Purpose: Other
Official 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
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : October 15, 2018
Estimated Study Completion Date : December 15, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Active Comparator: Normal Subjects, Gluten Drink
Normal subjects will drink a solution containing 6 grams of gluten one time.
Dietary Supplement: Gluten
Six grams of gluten will be mixed with water and Tang flavoring. Subjects will drink the mixture one time.

Placebo Comparator: Normal Subjects, Placebo Drink
Normal subjects will drink a solution without gluten one time.
Dietary Supplement: Placebo
Subjects will drink a mixture of rice water and Tang flavoring one time.

Active Comparator: Celiac Subjects, Gluten Drink
Subjects with celiac disease will drink a solution containing 6 grams of gluten one time.
Dietary Supplement: Gluten
Six grams of gluten will be mixed with water and Tang flavoring. Subjects will drink the mixture one time.

Placebo Comparator: Celiac Subjects, Placebo Drink
Subjects with celiac disease will drink a solution without gluten one time.
Dietary Supplement: Placebo
Subjects will drink a mixture of rice water and Tang flavoring one time.

Active Comparator: Gluten Sensitivity, Gluten Drink
Subjects with non-celiac gluten sensitivity will drink a solution containing 6 grams of gluten one time.
Dietary Supplement: Gluten
Six grams of gluten will be mixed with water and Tang flavoring. Subjects will drink the mixture one time.

Placebo Comparator: Gluten Sensitivity, Placebo Drink
Subjects with non-celiac gluten sensitivity will drink a solution without gluten one time.
Dietary Supplement: Placebo
Subjects will drink a mixture of rice water and Tang flavoring one time.




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288831


Contacts
Contact: Carol Van Dyke, CCRP 507-266-7842 VanDyke.Carol@mayo.edu
Contact: Amanda K Cartee, M.D. 507-255-6930 cartee.amanda@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Carol Van Dyke, CCRP    507-266-7842    VanDyke.Carol@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Joseph A. Murray, M.D. Mayo Clinic

Publications:

Responsible Party: Joseph A. Murray, M.D., Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03288831     History of Changes
Other Study ID Numbers: IRB 17-003596
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: November 22, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joseph A. Murray, M.D., Mayo Clinic:
Randomized, double-blinded, placebo-controlled trial
Oral food challenge

Additional relevant MeSH terms:
Celiac Disease
Intestinal Diseases
Duodenal Diseases
Immune System Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases
Hypersensitivity
Wheat Hypersensitivity
Malabsorption Syndromes
Food Hypersensitivity
Hypersensitivity, Immediate