Serum Markers in Gluten Challenge

NCT00931892 | Completed Results

• 2 other identifiers: 2007P000280K23DK082619
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.The purpose of this research study is to evaluate non-invasive markers of celiac disease activity in subjects that are on a gluten-free diet, in remission from celiac disease who undergo gluten challenge.
2. 2.The secondary aims of this protocol are to identify novel mediators important in the pathophysiology of celiac disease and to evaluate changes in metabolism with gluten exposure.

Conditions

Celiac Disease

Keywords

celiac disease; gluten challenge

Outcome Measures

Primary Outcomes (1)

• Crypt Depth to Villous Height Ratio

  Histological evaluation of duodenal biopsy samples to evaluate crypt depth to villous height ratio. On the best oriented section of each biopsy fragment, villous height to crypt depth (Vh:Cd) ratio was determined by measuring the mean height /mean depth of adjacent villi/proliferative crypt zones at magnification 100x. Evaluations were considered discrepant Vh:Cd differed by more than 0.5. Overall, there was excellent concordance with the evaluations of the 165 biopsy fragments determined to be optimal for evaluation. The Vh:Cd ratios on individual biopsies from a single averaged to produce a representative Vh:Cd ratio for each endoscopy. Normal Vh:Cd ratio was regarded as 3:1 or greater. Adelman DC, Murray J, Wu TT, Mäki M, Green PH, Kelly CP. Measuring Change In Small Intestinal Histology In Patients With Celiac Disease. Am J Gastroenterol. 2018 Mar;113(3):339-347. doi: 10.1038/ajg.2017.480. Epub 2018 Feb 20. Review. PubMed PMID: 29460921.

  Screening (Day -7 to -14), Day 3, Day 14

Secondary Outcomes (7)

• Count of Intraepithelial Lymphocytes Per 100 Enterocytes in Duodenal Biopsy Samples

  Screening (Day -7 to -14), Day 3, Day 14

• Measures of Intestinal Permeability (Urinary Lactulose to Mannitol Ratio)

  Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28

• Measures of Immune Activation

  Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28

• Assessment of Protein Expression in Intestinal Biopsies

  Screening (Day -7 to -14), Day 3, Day 14

• Symptomatic Response to Gluten Exposure Determined by Celiac Symptom Index Questionnaire

  Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28

Study Arms (2)

Low gluten group

EXPERIMENTAL

Subjects will eat 3g of gluten per day

Dietary Supplement: Gluten

High gluten group

EXPERIMENTAL

Subjects will eat 10g of gluten per day

Dietary Supplement: Gluten

Interventions

Gluten DIETARY_SUPPLEMENT

3g

Low gluten group

Eligibility Criteria

• Age: 17 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 17 and 72 years, inclusive.
• Subject must have been diagnosed with celiac disease by duodenal / jejunal biopsy at least 6 months prior to entrance into the study.
• Subject has Anti-Tissue Transglutaminase (anti-tTG) ≤ 20 EU as measured by serology.
• Subject must be on a gluten-free diet for at least the past 6 months.
• Female subjects should be either post-menopausal (amenorrhea for at least 24 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) with a negative urine beta human chorionic gonadotropin (HCG) pregnancy test prior to entering the study and who are using or agree to use acceptable methods of contraception. Abstinence is an acceptable means of avoiding pregnancy as long as the subject agrees to use contraception if they become sexually active. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depo, patch or injectable) in use for one month prior to screening and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
• Subject must sign an Institutional Review Board approved informed consent and agree to complete required clinic visits.
• BMI between 18.5 and 38, inclusive.

You may not qualify if:

• Subject has Anti-Tissue Transglutaminase (anti-tTG) \> 20 EU as measured by serology.
• Subject has other food intolerances or food allergies (other than celiac disease) that would interfere with the conduct of the study).
• Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion
• Subject has any chronic active GI disease other than celiac disease (e.g. Crohn's disease, IBS).
• Subjects with symptomatic neurological or psychiatric disease(s) that would interfere with the conduct of the study.
• Subject has clinically significant abnormal laboratory test results at the screening visit or as determined by the Principal Investigator
• Subject is pregnant or breast feeding.
• Subject (premenopausal females) is sexually active without contraception.
• Subject should not have been on steroids in the past 3 months.
• Subject is deemed inappropriate by the Principal Investigator.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (4)

• Svedlund J, Sjodin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988 Feb;33(2):129-34. doi: 10.1007/BF01535722.

  PMID: 3123181 BACKGROUND

• Adelman DC, Murray J, Wu TT, Maki M, Green PH, Kelly CP. Measuring Change In Small Intestinal Histology In Patients With Celiac Disease. Am J Gastroenterol. 2018 Mar;113(3):339-347. doi: 10.1038/ajg.2017.480. Epub 2018 Feb 20.

  PMID: 29460921 RESULT

• Leffler DA, Dennis M, Edwards George J, Jamma S, Cook EF, Schuppan D, Kelly CP. A validated disease-specific symptom index for adults with celiac disease. Clin Gastroenterol Hepatol. 2009 Dec;7(12):1328-34, 1334.e1-3. doi: 10.1016/j.cgh.2009.07.031. Epub 2009 Aug 7.

  PMID: 19665584 RESULT

• 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 DERIVED

Related Links

• BIDMC Celiac Center Research website

MeSH Terms

Conditions

Celiac Disease

Interventions

Glutens

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This study did have few limitations. First, the study was only moderate in size and drawn from a single center. Many subjects had significant inflammation on duodenal biopsy at baseline which may have limited the effect of gluten challenge. Finally, the high and low gluten groups were significantly different in a few factors including time since diagnosis, time on a gluten-free diet and GSRS score.

Results Point of Contact

• Title: Dr. Ciaran Kelly
• Organization: Beth Israel Deaconess Medical Center

ckelly2@bidmc.harvard.edu

617-667-1272

Study Officials

• Ciaran P Kelly, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

• Daniel A Leffler, MD, MS

  Beth Israel Deaconess Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 30, 2009
• First Posted: July 2, 2009
• Study Start: April 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 4, 2021
• Results First Posted: June 4, 2021

Record last verified: 2021-05

Locations

US (1)