Prebiotic as a Supplement of Gluten-free Diet in the Management of Celiac Disease in Children

Study Overview
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Brief Summary
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Prebiotics are known as substances affecting beneficially the organism by restoring the intestinal microbiota balance, stabilizing the intestinal barrier and modulating the endocrine and immune functions. In many persons suffering from celiac disease (CD), despite a gluten-free diet (GFD), an impaired intestinal barrier functionality, accompanied by altered intestinal microbiota and ongoing intestinal inflammation is observed. For these reasons, prebiotic could be a promising and low-risk adjuvant in the dietetic management of CD. It was hypothesize that prebiotic preparation Synergy 1 consumed by CD children as a supplement of a GFD will affect beneficial the intestinal permeability and intestinal microbiota without side effects.

Detailed Description
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Prebiotics, including inulin-type fructans (ITFs) are a group of the naturally occurring plant carbohydrates stored in various amounts in tubers, bulbs and tuberous roots of several edible fruits and vegetables and in particularly large amounts in the tubers of Helianthus tuberosus (Jerusalem artichoke) and Cichorium intybus (chicory). Because of their unique structural properties, they are not hydrolyzed by the enzymes of the upper intestinal digestive tract and reach the colon unchanged, therefore are classified as prebiotics. Prebiotics are defined as selectively fermented ingredients that allow specific changes in the composition and/or balance of the microbiota. ITFs, particularly the mixture of short- and long-chain polymers, indicate several beneficial effects, including the positive changes in the histological picture of the intestine (proliferation in the crypts and Goblet cells, longer intestinal villi) and modulation of the endocrine and immune functions. Moreover, they have a great potential as agents improving or maintaining a balanced intestinal microbiota both in the lumen and at the mucosal surface, to one in which bifidobacteria and lactobacilli come to greater prominence. This, so-called healthier flora, should provide increased resistance to gut infections and may also have immuno-modulatory properties. Until now, inulin and fructooligosaccharide (FOS) have been tested mainly in animal models of inflammatory bowel diseases (IBD). Reports on animal colitis model suggests that prebiotics have the anti-inflammatory properties as they reduce the inflammation symptoms, along with the increase in bifidobacteria or lactobacilli number, and in some reports, the increase in the concentration of butyrate in the gut. Prebiotics are known as substances affecting beneficially the organism by restoring the intestinal microbiota balance, stabilizing the intestinal barrier and modulating the endocrine and immune functions. In many persons suffering from celiac disease (CD), despite a gluten-free diet (GFD), an impaired intestinal barrier functionality, accompanied by altered intestinal microbiota and ongoing intestinal inflammation is observed. For these reasons, prebiotics could be a promising and low-risk adjuvant in the dietetic management of CD. It was hypothesized that Synergy 1 consumed by CD children as a supplement of a GFD will affect beneficial the intestinal permeability and intestinal microbiota without side effects. The primary objective of this randomized placebo-controlled study was to determine the effect of 3-months consumption of Synergy 1 versus placebo, as the supplements of a GFD, on the intestinal permeability in CD children, in particular on the concentration of the intestinal fatty acid binding protein (iFABP) as a biomarker of intestinal permeability. The secondary objective was to determine the effect of Synergy 1 versus placebo applied in GFD on the changes in the gut microbiota quantity and metabolism in CD children.

Official Title
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Assessment of the Impact of Prebiotic Synergy 1 on the Intestine Permeability, Clinical Symptoms, and Selected Biochemical and Nutritional Parameters in the Children With Celiac Disease on a Gluten-free Diet

Conditions
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Celiac Disease

Intervention / Treatment
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* Dietary Supplement: Synergy 1
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: celiac disease treatment with gluten-free diet for at least 6 months general good health the written informed consent to participate the study Exclusion Criteria: participation in another study involving prebiotic and/or probiotic preparations, or intention to use such products during the course of the study other gastrointestinal diseases received antibiotics in the previous month use of dietary supplements containing prebiotic or/and probiotic within the previous month bad or average overall health

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prebiotic Synergy 1-supplemented GFD<br>The application of a prebiotic Synergy 1 together with a strict gluten-free diet | Dietary Supplement: Synergy 1<br>* a daily dose: 7 g/day of Synergy1 (oligofructose enriched inulin) consumed for 12 weeks together with a strict gluten-free diet<br>|
| Placebo Comparator: Placebo-supplemented GFD<br>The application of a placebo together with a strict gluten-free diet | Dietary Supplement: Placebo<br>* a daily dose: 7 g/day of placebo (maltodextrin) consumed for 12 weeks together with a strict gluten-free diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the intestinal permeability | Changes in the concentration of intestinal fatty acid binding protein (iFABP) as a biomarker of intestinal permeability will be determined | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the advers events | A number of participants with adverse events related to the treatment will be recorded | 6 months | 
| Analysis of the concentration of the short chain fatty acids (SCFAs) | Changes in the concentration and a profile of the short chain fatty acids (SCFAs) using gas chromatography | 6 month | 
| Molecular characteristic of faecal microbiota | Quantitative characteristics of faecal bacteria will be conducted with the real-time polymerase chain reaction (RT-PCR) technique and group-specific primers. Population level of Bifidobacterium, Bacteroides, Clostridium coccoides, C. leptum and E. coli groups will be determined among others. | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prebiotic, pediatric patients, health status, intestine permeability