- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03288831
Changes in Intestinal Permeability 4 Hours After Gluten Challenge
June 5, 2019 updated by: Joseph A. Murray, M.D., Mayo Clinic
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
60
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Normal Subjects, Gluten Drink
Normal subjects will drink a solution containing 6 grams of gluten one time.
|
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.
|
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.
|
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.
|
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.
|
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.
|
Subjects will drink a mixture of rice water and Tang flavoring one time.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
4 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and up to eight hours after gluten or placebo exposure
|
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.
|
Baseline and up to 72 hours after gluten or placebo exposure
|
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.
|
Baseline and up to 72 hours after gluten or placebo exposure
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Joseph A. Murray, M.D., Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Leffler D, Schuppan D, Pallav K, Najarian R, Goldsmith JD, Hansen J, Kabbani T, Dennis M, Kelly CP. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut. 2013 Jul;62(7):996-1004. doi: 10.1136/gutjnl-2012-302196. Epub 2012 May 22.
- Adriaanse MP, Tack GJ, Passos VL, Damoiseaux JG, Schreurs MW, van Wijck K, Riedl RG, Masclee AA, Buurman WA, Mulder CJ, Vreugdenhil AC. Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies. Aliment Pharmacol Ther. 2013 Feb;37(4):482-90. doi: 10.1111/apt.12194. Epub 2013 Jan 7.
- Anderson RP, van Heel DA, Tye-Din JA, Barnardo M, Salio M, Jewell DP, Hill AV. T cells in peripheral blood after gluten challenge in coeliac disease. Gut. 2005 Sep;54(9):1217-23. doi: 10.1136/gut.2004.059998.
- Camarca A, Radano G, Di Mase R, Terrone G, Maurano F, Auricchio S, Troncone R, Greco L, Gianfrani C. Short wheat challenge is a reproducible in-vivo assay to detect immune response to gluten. Clin Exp Immunol. 2012 Aug;169(2):129-36. doi: 10.1111/j.1365-2249.2012.04597.x.
- Beitnes AC, Raki M, Brottveit M, Lundin KE, Jahnsen FL, Sollid LM. Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge. PLoS One. 2012;7(3):e33556. doi: 10.1371/journal.pone.0033556. Epub 2012 Mar 16.
- Jansson UH, Kristiansson B, Magnusson P, Larsson L, Albertsson-Wikland K, Bjarnason R. The decrease of IGF-I, IGF-binding protein-3 and bone alkaline phosphatase isoforms during gluten challenge correlates with small intestinal inflammation in children with coeliac disease. Eur J Endocrinol. 2001 Apr;144(4):417-23. doi: 10.1530/eje.0.1440417.
- Greco L, D'Adamo G, Truscelli A, Parrilli G, Mayer M, Budillon G. Intestinal permeability after single dose gluten challenge in coeliac disease. Arch Dis Child. 1991 Jul;66(7):870-2. doi: 10.1136/adc.66.7.870.
- Horvath K, Nagy L, Horn G, Simon K, Csiszar K, Bodanszky H. Intestinal mast cells and neutrophil chemotactic activity of serum following a single challenge with gluten in celiac children on a gluten-free diet. J Pediatr Gastroenterol Nutr. 1989 Oct;9(3):276-80. doi: 10.1097/00005176-198910000-00003.
- Kontakou M, Przemioslo RT, Sturgess RP, Limb GA, Ellis HJ, Day P, Ciclitira PJ. Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge. Gut. 1995 Jul;37(1):52-7. doi: 10.1136/gut.37.1.52.
- Strobel S, Busuttil A, Ferguson A. Human intestinal mucosal mast cells: expanded population in untreated coeliac disease. Gut. 1983 Mar;24(3):222-7. doi: 10.1136/gut.24.3.222.
- Cartee AK, Choung RS, King KS, Wang S, Dzuris JL, Anderson RP, Van Dyke CT, Hinson CA, Marietta E, Katzka DA, Nehra V, Grover M, Murray JA. Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity. Am J Gastroenterol. 2022 Feb 1;117(2):319-326. doi: 10.14309/ajg.0000000000001565.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
October 10, 2017
Primary Completion (ACTUAL)
October 30, 2018
Study Completion (ACTUAL)
October 30, 2018
Study Registration Dates
First Submitted
September 18, 2017
First Submitted That Met QC Criteria
September 18, 2017
First Posted (ACTUAL)
September 20, 2017
Study Record Updates
Last Update Posted (ACTUAL)
June 7, 2019
Last Update Submitted That Met QC Criteria
June 5, 2019
Last Verified
June 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB 17-003596
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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