Randomized Clincal Trial on the Effect of a Restricted Gluten Contamination Elimination Diet Among Celiacs [GluCED]

Study Overview
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Brief Summary
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The study assessed whether compete healing of duodenal mucosa in celiac patients with persistent Marsh I-II lesion after 1 year of gluten free diet (GFD): could be achieved by adoption of a diet based exclusively on naturally gluten free products, with the elimination of commercially available processed food (GCED, Gluten Contamination Elimination Diet); may depend upon time of exposure to GFD. Investigators studied two cohorts of celiac patients, both on GFD, for at least one year: cohort A: patients re-biopsied after three months on GCED; cohort B: patients re-biopsied after a minimum of further two years on standard GFD.

Detailed Description
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Despite strict adherence to gluten free diet (GFD), the complete healing of the duodenal mucosa of celiac patients is rarely achieved. The cause of the persistence of the inflammation is not yet understood. It is well known that there is a high degree of variability in individual response to gluten with some patients worsening of duodenal histology upon exposure to very small amount of gluten. This observation suggest that contamination with gluten of commercially available processed food and/or small amount of gluten in processed foods labeled gluten-free (less than 20 ppm) may prevent complete mucosal healing. This explanation is indirectly supported by a study of Hollon et al. (2013) showing that persistence of gastrointestinal symptoms in celiac patients on a GFD is abolished, in 85% of cases, by the adoption of a diet based exclusively on naturally gluten-free products, and on the elimination from the diet of commercially available processed food and products labeled gluten free  (Gluten Contamination Elimination Diet, GCED). The main aim of this study was to assess whether the complete healing of duodenal mucosa in patients with persistent Mars I-II lesions after 1 year on GFD i) could be achieved, as a proof of the concept, by the adoption of a GCED OR ii) may depend upon time of exposure to GFD. To achieve this aim investigators studied 2 cohorts of patients with Marsh I-II lesion after 1 year on GFD: cohort A re-byopsied after 3 month GCED , and cohort B re-biopsied after a minimum of further 2 years on standard GFD.

Official Title
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Randomized Clincal Trial on the Effect of a Restricted Gluten Contamination Elimination Diet in Achieving Complete Mucosal Healing Among Celiac Patients With Persisting Minimal Duodenal Lesions During Gluten Free Diet [GluCED]

Conditions
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Celiac Disease

Intervention / Treatment
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* Behavioral: GCED, Gluten Contamination Elimination Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Marsh I-II lesion at 12-18 months after starting GFD Negative Celiac Disease serology Strict adherence to gluten free diet without digression Exclusion Criteria: presence of Gastrointestinal Symtoms presence of Helicobacter pylori infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A, GCED cohort<br>GCED, Gluten Contamination Elimination Diet | Behavioral: GCED, Gluten Contamination Elimination Diet<br>* A Gluten Free diet based exclusively on naturally gluten-free products and foods, with the elimination from the diet of all commercially available processed food and products labeled gluten free  (Gluten Contamination Elimination Diet, GCED).<br>|
| No Intervention: B, time cohort<br>Cohort B consisted of patients on long term follow-up that accepted a repeated biopsies 60 or more months later the first control biopsy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histologic classification | Assessment of Marsh class (0-I-II-III) on duodenal biopsies in participants from both cohorts | three months in cohort A, at least sixty months in cohort B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Celiac disease serology | IgA t-TG (class A Antibodies anti tissue Transglutaminases) were measured in particiapnts serum at the same time of dudenal biopsy [Eu t-Tg Eurospital, Trieste, Italy] | three months in cohort A, at least sixty months in cohort B | 
| TCR+ T cells count | TCR+ T cells were identified using a commercially available method suitable for formalin fixed paraffin embedded dudenal biopsies. A mean of the count of TCR+T cells was obtained with a cut-off value of 4 out of 100 epithelial cells. | three months in cohort A, sixty months in cohort B | 
| Eosinophils count | Eosinophils were identified and counted on duodenal biopsies with a cut off value of 2 out of 100 epithelial cells. | three months in cohort A, sixty months in cohort B | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Celiac Disease,, Gluten Free Diet, Gluten contamination