Changes in Intestinal Permeability 4 Hours After Gluten Challenge

NCT03288831 | Completed DMC

• 1 other identifier: IRB 17-003596
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Changes in Mucosal Permeability after Oral Gluten Challenge

  Baseline and up to eight hours after gluten or placebo exposure

• Detection of Gluten Peptides in Urine and Stool

  Baseline and up to 72 hours after gluten or placebo exposure

• Rapid Onset Symptom Development after Gluten Exposure

  Baseline and up to 72 hours after gluten or placebo exposure

Study Arms (6)

Normal Subjects, Gluten Drink

ACTIVE COMPARATOR

Normal subjects will drink a solution containing 6 grams of gluten one time.

Dietary Supplement: Gluten

Normal Subjects, Placebo Drink

PLACEBO COMPARATOR

Normal subjects will drink a solution without gluten one time.

Dietary Supplement: Placebo

Celiac Subjects, Gluten Drink

ACTIVE COMPARATOR

Subjects with celiac disease will drink a solution containing 6 grams of gluten one time.

Dietary Supplement: Gluten

Celiac Subjects, Placebo Drink

PLACEBO COMPARATOR

Subjects with celiac disease will drink a solution without gluten one time.

Dietary Supplement: Placebo

Gluten Sensitivity, Gluten Drink

ACTIVE COMPARATOR

Subjects with non-celiac gluten sensitivity will drink a solution containing 6 grams of gluten one time.

Dietary Supplement: Gluten

Gluten Sensitivity, Placebo Drink

PLACEBO COMPARATOR

Subjects with non-celiac gluten sensitivity will drink a solution without gluten one time.

Dietary Supplement: Placebo

Interventions

Gluten DIETARY_SUPPLEMENT

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

Celiac Subjects, Gluten Drink; Gluten Sensitivity, Gluten Drink; Normal Subjects, Gluten Drink

Placebo DIETARY_SUPPLEMENT

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

Celiac Subjects, Placebo Drink; Gluten Sensitivity, Placebo Drink; Normal Subjects, Placebo Drink

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (11)

• 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.

  PMID: 22619366 BACKGROUND

• 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.

  PMID: 23289539 BACKGROUND

• 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.

  PMID: 16099789 BACKGROUND

• 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.

  PMID: 22774987 BACKGROUND

• 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.

  PMID: 22438948 BACKGROUND

• 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.

  PMID: 11275953 BACKGROUND

• 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.

  PMID: 1863103 BACKGROUND

• 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.

  PMID: 2614612 BACKGROUND

• 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.

  PMID: 7672681 BACKGROUND

• 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.

  PMID: 6826106 BACKGROUND

• 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.

  PMID: 34797778 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Celiac Disease; Wheat Hypersensitivity; Duodenal Diseases

Interventions

Glutens

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Prolamins; Grain Proteins; Plant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Seed Storage Proteins

Study Officials

• Joseph A. Murray, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subjects will be block randomized to either gluten-containing or placebo challenge.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Randomized, double-blinded, placebo-controlled oral gluten challenge

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 20, 2017
• Study Start: October 10, 2017
• Primary Completion: October 30, 2018
• Study Completion: October 30, 2018
• Last Updated: June 7, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)