Changes in Intestinal Permeability 4 Hours After Gluten Challenge

Celiac Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03288831
• Other study ID #: IRB 17-003596
• Status: Completed
• Phase: N/A
• Start date: October 10, 2017
• Est. completion date: October 30, 2018

Study information

• Verified date: June 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 30, 2018
• Est. primary completion date: October 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Celiac Disease
• Duodenal Diseases
• Gluten Enteropathy
• Gluten Sensitivity
• Hypersensitivity
• Immune System and Related Disorders
• Intestinal Diseases
• Wheat Hypersensitivity

Intervention

Dietary Supplement:
• Gluten
Six grams of gluten will be mixed with water and Tang flavoring. Subjects will drink the mixture one time.
• Placebo
Subjects will drink a mixture of rice water and Tang flavoring one time.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View 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. — View Citation

Beitnes AC, Ráki 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. — View 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. — View 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. — View Citation

Horváth K, Nagy L, Horn G, Simon K, Csiszár K, Bodánszky 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Activation of the Mucosal Innate Immune System after Oral Gluten Challenge	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	Changes in Mucosal Permeability after Oral Gluten Challenge	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
Secondary	Detection of Gluten Peptides in Urine and Stool	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
Secondary	Rapid Onset Symptom Development after Gluten 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

External Links

•   Mayo Clinic Clinical Trials