Serum Markers in Gluten Challenge

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00931892
First received: June 30, 2009
Last updated: July 22, 2014
Last verified: July 2014
  Purpose
  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. 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.

Condition Intervention
Celiac Disease
Dietary Supplement: Gluten

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Circulating Markers of Celiac Disease Activity During Gluten Challenge - a Pilot Study.

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Histological evaluation of duodenal biopsy samples to evaluate crypt depth to villous height ratio [ Time Frame: Screening (Day -7 to -14), Day 3, Day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Histological evaluation of duodenal biopsy samples to determine the number of intraepithelial lymphocytes per 100 enterocytes [ Time Frame: Screening (Day -7 to -14), Day 3, Day 14 ] [ Designated as safety issue: No ]
  • Measures of intestinal permeability (urinary lactulose to mannitol ratio) and malabsorption (plasma prealbumin) [ Time Frame: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28 ] [ Designated as safety issue: No ]
  • Measures of immune activation (tTG, cytokines) [ Time Frame: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28 ] [ Designated as safety issue: No ]
  • Assessment of protein expression in intestinal biopsies [ Time Frame: Screening (Day -7 to -14), Day 3, Day 14 ] [ Designated as safety issue: No ]
  • Symptomatic response to gluten exposure determined by questionnaire [ Time Frame: Screening (Day -7 to -14), Day 0, Day 3, Day 7, Day 14, Day 28 ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: April 2009
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low gluten group
Subjects will eat 3g of gluten per day
Dietary Supplement: Gluten
3g
Experimental: High gluten group
Subjects will eat 10g of gluten per day
Dietary Supplement: Gluten
10g

Detailed Description:

The diagnosis of celiac disease carries with it important ramifications. Celiac disease is a systemic immunologic disorder in which the sentinel lesion is an enteropathy triggered by polypeptides derived primarily from the gliadin proteins found in wheat, rye and barley. Ingestion of the offending proteins leads to inflammation and intestinal mucosal damage, which results in a spectrum of abdominal symptoms, increased intestinal permeability, malabsorption, occult gastrointestinal bleeding and diarrhea. Systemic manifestations of celiac disease include a myriad of conditions including malignancy and autoimmune disease.

The only accepted treatment for celiac disease is lifelong adherence to a gluten free diet. Adherence to this diet, simply put avoiding all foods containing even small amounts of wheat, rye and barley, has been shown to lead to improvement in the majority of related problems and normalization of all standard diagnostic tests. Because of this many individuals who present for evaluation of possible celiac disease but who are already on a gluten free diet cannot be tested accurately as there is currently no way of differentiating between healthy individuals and individuals with well treated celiac disease. The standard practice in such cases is to perform a 'Gluten Challenge' whereby the patient eats the equivalent of 2 slices of bread per day for six to eight weeks before returning for evaluation with serologic testing and endoscopy with duodenal biopsy. The use of the gluten challenge in clinical practice is limited by patient symptoms and resistance to such a long test period, after which it may take a number of weeks for the intestine to heal and the symptoms to resolve. Autoantibodies to tissue transglutaminase or antibodies to deamidated gliadin, while being excellent tools to predict celiac disease in patients who have been on a long-term gluten containing diet, display low sensitivities to detect short-term and/or recent gluten exposure. For this reason, it would be very useful if novel circulating markers could be identified that indicate the presence of celiac disease and in particular would provide an early and less invasive marker of a positive response to gluten challenge.

  Eligibility

Ages Eligible for Study:   17 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 17 and 72 years, inclusive.
  2. Subject must have been diagnosed with celiac disease by duodenal / jejunal biopsy at least 6 months prior to entrance into the study.
  3. Subject has Anti-Tissue Transglutaminase (anti-tTG) ≤ 20 EU as measured by serology.
  4. Subject must be on a gluten-free diet for at least the past 6 months.
  5. 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.
  6. Subject must sign an Institutional Review Board approved informed consent and agree to complete required clinic visits.
  7. BMI between 18.5 and 38, inclusive.

Exclusion Criteria:

  1. Subject has Anti-Tissue Transglutaminase (anti-tTG) > 20 EU as measured by serology.
  2. Subject has other food intolerances or food allergies (other than celiac disease) that would interfere with the conduct of the study).
  3. Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion
  4. Subject has any chronic active GI disease other than celiac disease (e.g. Crohn's disease, IBS).
  5. Subjects with symptomatic neurological or psychiatric disease(s) that would interfere with the conduct of the study.
  6. Subject has clinically significant abnormal laboratory test results at the screening visit or as determined by the Principal Investigator
  7. Subject is pregnant or breast feeding.
  8. Subject (premenopausal females) is sexually active without contraception.
  9. Subject should not have been on steroids in the past 3 months.
  10. Subject is deemed inappropriate by the Principal Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931892

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Ciaran P Kelly, MD Beth Israel Deaconess Medical Center
Study Director: Daniel A Leffler, MD, MS Beth Israel Deaconess Medical Center
  More Information

No publications provided by Beth Israel Deaconess Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00931892     History of Changes
Other Study ID Numbers: 2007-P-000280
Study First Received: June 30, 2009
Last Updated: July 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
celiac disease
gluten challenge

Additional relevant MeSH terms:
Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on July 23, 2014