Clinical trial NCT03288831: Changes in Intestinal Permeability 4 Hours After Gluten Challenge
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Celiac Disease
Wheat Hypersensitivity
Gluten Sensitivity
Gluten Enteropathy
Immune System and Related Disorders
Duodenal Diseases
Keywords: Randomized, double-blinded, placebo-controlled trial
Oral food challenge
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2017-09-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, placebo-controlled oral gluten challenge
Primary purpose: OTHER

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.

Eligibility 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).

Primary outcomes:
measure: Activation of the Mucosal Innate Immune System after Oral Gluten Challenge
timeFrame: 4 hours
Secondary outcomes:
measure: Changes in Mucosal Permeability after Oral Gluten Challenge
timeFrame: Baseline and up to eight hours after gluten or placebo exposure
measure: Detection of Gluten Peptides in Urine and Stool
timeFrame: Baseline and up to 72 hours after gluten or placebo exposure
measure: Rapid Onset Symptom Development after Gluten Exposure
timeFrame: Baseline and up to 72 hours after gluten or placebo exposure
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Joseph A. Murray, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.