Trial record 12 of 29 for:    Open Studies | "Malabsorption Syndromes" | United States

Noninvasive Markers of Gluten Ingestion in Celiac Disease Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Thomas Jefferson University
Sponsor:
Information provided by (Responsible Party):
Jeff GI, Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT02389062
First received: February 12, 2015
Last updated: March 9, 2015
Last verified: March 2015
  Purpose
This is a clinical trial to evaluate the sensitivity of noninvasive, novel markers of gluten ingestion in celiac disease patients who are following gluten free diet for at least a period of one year. These noninvasive markers may be helpful to monitor the silent intestinal damage, possibly resulting from the accidental consumption of gluten due to cross contamination of gluten free diet.

Condition Intervention
Adult Form of Celiac Disease
Other: Administration of gluten( food /wheat protein) capsules or placebo(cornstarch) capsules and tests for novel markers will be done at intervals.

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Noninvasive Markers of Gluten Ingestion in Celiac Disease Patients: Prospective, Randomized,Placebo Controlled, Double Blind Clinical Trial

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • 1) Change in the patient estimated gluten intake after administration of study pills using the Celiac Dietary Adherence Test (CDAT), to be assessed at the end of follow up week 12 [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 2) Change in the Celiac disease symptoms, using the Celiac Symptom Index (CSI) after administration of study pills; to be assessed at the end of follow up week 12 [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 3)Change in IgA antibody to tissue transglutaminase (IgA-TTG) levels after administration of study pills, to be assessed at the end of follow up week 12. [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 4) Change in Intestinal fatty acid binding protein (I-FABP) levels after administration of study pills, to be assessed at the end of follow up week 12. [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 5)Change in stool gluten intestinal peptide (GIP) level after administration of study pills, to be assessed at the end of follow up week 12 [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 6)Change in urine gluten intestinal peptide (GIP) level after administration of study pills,to be assessed at the end of follow up week 12 [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]
  • 7)Change in patient estimated gluten intake(PEGI) after administration of study pills, using separate questionnaire, to be assessed at the end of follow up week 12 [ Time Frame: up to follow up week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: February 2015
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo controlled group
This is a group of same number of subjects as in other arms, who will be given equivalent dose of placebo- cornstarch capsules i.e 5 capsules containing neutral substance- cornstarch(placebo) to be taken daily by mouth for a period of 12 weeks.
Other: Administration of gluten( food /wheat protein) capsules or placebo(cornstarch) capsules and tests for novel markers will be done at intervals.
After administering the capsules for 16 weeks during study periods, patients's blood will be tested for novel markers- Intestinal fatty acid binding protein(I-FABP), stool for gluten intestinal peptide (GIP), urine for gluten intestinal peptide(GIP), patient estimated gluten intake(PEGI), celiac severity index(CSI), Celiac dietary adherence test(CDAT) by standard questionnaire provided during the visits. These tests will be done over a period of 16 weeks and at a follow up 3 months later.
Experimental: High dose gluten capsules
This group of subjects will be given high dose i.e 2.5 g of gluten containing capsules, 5 capsules to be taken daily by mouth, for a period of 12 weeks.
Other: Administration of gluten( food /wheat protein) capsules or placebo(cornstarch) capsules and tests for novel markers will be done at intervals.
After administering the capsules for 16 weeks during study periods, patients's blood will be tested for novel markers- Intestinal fatty acid binding protein(I-FABP), stool for gluten intestinal peptide (GIP), urine for gluten intestinal peptide(GIP), patient estimated gluten intake(PEGI), celiac severity index(CSI), Celiac dietary adherence test(CDAT) by standard questionnaire provided during the visits. These tests will be done over a period of 16 weeks and at a follow up 3 months later.
Experimental: Low dose gluten capsules
This group of subjects will be given low dose i.e 0.5 g of gluten containing capsules, 5 capsules to be taken daily by mouth, for a period of 12 weeks.
Other: Administration of gluten( food /wheat protein) capsules or placebo(cornstarch) capsules and tests for novel markers will be done at intervals.
After administering the capsules for 16 weeks during study periods, patients's blood will be tested for novel markers- Intestinal fatty acid binding protein(I-FABP), stool for gluten intestinal peptide (GIP), urine for gluten intestinal peptide(GIP), patient estimated gluten intake(PEGI), celiac severity index(CSI), Celiac dietary adherence test(CDAT) by standard questionnaire provided during the visits. These tests will be done over a period of 16 weeks and at a follow up 3 months later.

Detailed Description:

The gold-standard for monitoring of dietary adherence is consultation with an expert dietitian, but this may be time-consuming for patients and local expertise may not be available. Intestinal biopsy is the only direct method to document mucosal healing and can be considered in all adults with celiac disease. Non-invasive assessment of compliance with a gluten free diet(GFD) can be achieved with monitoring of IgA antibodies to tissue transglutaminase (IgA-tTG) or deamidated gliadin peptides, as these markers improve with gluten elimination. However, intestinal mucosal damage is present in a significant number of patients who report compliance with a gluten free diet and have normalized serology, potentially due to dietary lapses or unrecognized contamination with gluten. Furthermore, serologic testing may be normal in patients with partial adherence. Patient reported surveys show promise for assessing gluten free diet adherence, but further studies are needed.

Intestinal fatty acid-binding protein (I-FABP), a small (15 kD) cytosolic protein found exclusively in the small bowel enterocytes, has been studied as a marker of intestinal epithelial damage in septic shock and mesenteric ischemia. More recently, elevated levels of intestinal fatty acid-binding protein( I-FABP) have been described as a marker of intestinal injury in both adults and children with celiac disease. Intestinal fatty acid binding protein, (I-FABP) levels have been shown to significantly correlate with the degree of villous atrophy and IgA antibody to tissue transglutaminase (IgA-tTG), as well as decrease upon treatment with a gluten free diet(GFD). Incomplete normalization of intestinal fatty acid binding protein(I-FABP) on a gluten free diet points to ongoing intestinal injury, even in the absence of circulating antibodies, thus suggesting its potential as a non-invasive marker for gluten free diet adherence and intestinal damage in celiac disease.

The measurement of gluten immunogenic peptides (GIP) in stool is a novel method to monitor gluten free diet compliance. Recently, a technique to detect gliadin 33-mer equivalent peptide epitopes (33EPs) in the stool of pediatric patients has been described. These peptides show significant resistance to digestion and were detected in healthy individuals after normal gluten-containing diet ingestion. Importantly, these peptides are not detected in patients on a gluten free diet, and there appears to be a correlation between the amount of gluten intake and the peptide levels. A similar test has been developed for gluten intestinal peptide(GIP) detection in urine, although there are currently no peer-reviewed studies examining this technique. Further research on the utility of stool and urine gluten intestinal peptide (GIP)for monitoring of gluten free diet (GFD) adherence is warranted.

Given the lack of a non-invasive and accurate measure of gluten intake in celiac disease (CD), the investigators will investigate the effect of gluten intake in celiac disease (CD) patients using a variety of markers. Patients who are symptom-free on a gluten free diet (GFD) will be exposed to various amounts of gluten. Factors that will be studied include the effect on patient estimated gluten intake, Celiac disease symptoms, IgA-tTG level,intestinal fatty acid binding protein( I-FABP) level, and both stool and urine gluten peptide levels.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • This study population will consist of patients with a prior diagnosis of celiac disease based on intestinal biopsy (Marsh score of 1-4) who report control of symptoms with adherence to gluten free diet(GFD) for at least one year and have a baseline IgA antibody to tissue transglutaminase(IgA-tTG) within the normal range.

Exclusion Criteria:

  • Patients < 18 years of age
  • Patients with refractory celiac disease (RFD), defined as persisting or recurring symptoms and mucosal villous atrophy, despite strict adherence to a gluten free diet (GFD) for >12 months and a negative IgA antibody to tissue transglutaminase (IgA-tTG)
  • Patients with enteropathy-associated T-cell lymphoma
  • Patients with IgA deficiency
  • Patients with a diagnosis of inflammatory bowel disease, irritable bowel symptoms, or acute gastroenteritis
  • Patients taking immunosuppressive medications
  • Patients who are pregnant
  • Patients who are breast feeding/lactating
  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: NCT02389062

Contacts
Contact: CYNTHIA MILLER, RN 215-955-8108 Cynthia.L.Miller.3@jefferson.edu

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Cynthia L Miller, RN    215-955-8108    Cynthia.L.Miller.3@jefferson.edu   
Contact: Ajini Cherian, RN    215-955-7979    Ajini.Cherian@jefferson.edu   
Principal Investigator: Anthony DiMarino, MD         
Sub-Investigator: Stephanie Moleski, MD         
Sub-Investigator: Colin Smith, MD         
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Anthony J. DiMarino, MD Thomas Jefferson University, Philadelphia, PA 19107
  More Information

Publications:
Rodriguez-Herrera A, Comino I, Real A, et al, Monitoring of gluten-free diet compliance in pediatric patients by fecal check; (Abstract #F613). Presented at the 15th International Celiac Disease Symposium. September, 2013. Chicago.

Responsible Party: Jeff GI, Professor, Chair, Division of Gastroenterology, Director, celiac disease center, Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT02389062     History of Changes
Other Study ID Numbers: 14D.389 
Study First Received: February 12, 2015
Last Updated: March 9, 2015
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on July 27, 2016