Noninvasive Markers of Gluten Ingestion in Celiac Disease Patients
Condition: Adult Form of Celiac Disease
MeSH terms: Celiac Disease
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Administration of gluten( food /wheat protein) capsules or placebo(cornstarch) capsules and tests for novel markers will be done at intervals.
Intervention type(s): Other
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic