Back to results

Changes in Intestinal Permeability 4 Hours After Gluten Challenge

Primary Purpose

Celiac Disease, Wheat Hypersensitivity, Gluten Sensitivity

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Gluten

Placebo

About this trial

This is an interventional other trial for Celiac Disease focused on measuring Randomized, double-blinded, placebo-controlled trial, Oral food challenge

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

Normal Subjects, Gluten Drink

Normal Subjects, Placebo Drink

Celiac Subjects, Gluten Drink

Celiac Subjects, Placebo Drink

Gluten Sensitivity, Gluten Drink

Gluten Sensitivity, Placebo Drink

Arm Description

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

Normal subjects will drink a solution without gluten one time.

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

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT03288831

First Posted

September 18, 2017

Last Updated

June 5, 2019

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT03288831

Brief Title

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

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

October 10, 2017 (Actual)

Primary Completion Date

October 30, 2018 (Actual)

Study Completion Date

October 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Randomized, double-blinded, placebo-controlled oral gluten challenge

Masking

ParticipantCare ProviderInvestigator

Masking Description

Subjects will be block randomized to either gluten-containing or placebo challenge.

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Subjects, Gluten Drink

Arm Type

Active Comparator

Arm Description

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

Arm Title

Normal Subjects, Placebo Drink

Arm Type

Placebo Comparator

Arm Description

Normal subjects will drink a solution without gluten one time.

Arm Title

Celiac Subjects, Gluten Drink

Arm Type

Active Comparator

Arm Description

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

Arm Title

Celiac Subjects, Placebo Drink

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Gluten Sensitivity, Gluten Drink

Arm Type

Active Comparator

Arm Description

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

Arm Title

Gluten Sensitivity, Placebo Drink

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Gluten

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Activation of the Mucosal Innate Immune System after Oral Gluten Challenge

Description

Time Frame

4 hours

Secondary Outcome Measure Information:

Title

Changes in Mucosal Permeability after Oral Gluten Challenge

Description

Time Frame

Baseline and up to eight hours after gluten or placebo exposure

Title

Detection of Gluten Peptides in Urine and Stool

Description

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.

Time Frame

Baseline and up to 72 hours after gluten or placebo exposure

Title

Rapid Onset Symptom Development after Gluten Exposure

Description

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.

Time Frame

Baseline and up to 72 hours after gluten or placebo exposure

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph A. Murray, M.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

22619366

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.

Results Reference

background

PubMed Identifier

23289539

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.

Results Reference

background

PubMed Identifier

16099789

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.

Results Reference

background

PubMed Identifier

22774987

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.

Results Reference

background

PubMed Identifier

22438948

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.

Results Reference

background

PubMed Identifier

11275953

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.

Results Reference

background

PubMed Identifier

1863103

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.

Results Reference

background

PubMed Identifier

2614612

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.

Results Reference

background

PubMed Identifier

7672681

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.

Results Reference

background

PubMed Identifier

6826106

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.

Results Reference

background

PubMed Identifier

34797778

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.

Results Reference

derived

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

Learn more about this trial

Changes in Intestinal Permeability 4 Hours After Gluten Challenge

We'll reach out to this number within 24 hrs