Clinical trial NCT03064997: Prebiotic as a Supplement of Gluten-free Diet in the Management of Celiac Disease in Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Celiac Disease
Keywords: prebiotic
pediatric patients
health status
intestine permeability
Lead sponsor: Polish Academy of Sciences
Sponsor class: OTHER
Collaborators: name: University of Warmia and Mazury
First posted: 2017-02-27
Enrollment: 34
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of the intestinal permeability
timeFrame: 6 months
Secondary outcomes:
measure: Assessment of the advers events
timeFrame: 6 months
measure: Analysis of the concentration of the short chain fatty acids (SCFAs)
timeFrame: 6 month
measure: Molecular characteristic of faecal microbiota
timeFrame: 6 month
Other outcomes:
Locations:
city: Olsztyn
country: Poland
facility: Regional Specialized Children'S Hospital
city: Olsztyn
country: Poland
facility: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences in Olsztyn
Study officials:
affiliation: Institute of Animal Reproduction and Food Reseach, Polish Academy of Sciences in Olsztyn
name: Urszula Krupa-Kozak, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Clinical Pediatrics, Faculty of Medical Sciences, University of Warmia and Mazury
name: Elżbieta Jarocka-Cyrta, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drabinska N, Jarocka-Cyrta E, Ratcliffe NM, Krupa-Kozak U. The Profile of Urinary Headspace Volatile Organic Compounds After 12-Week Intake of Oligofructose-Enriched Inulin by Children and Adolescents with Celiac Disease on a Gluten-Free Diet: Results of a Pilot, Randomized, Placebo-Controlled Clinical Trial. Molecules. 2019 Apr 5;24(7):1341. doi: 10.3390/molecules24071341.
citation: Drabinska N, Jarocka-Cyrta E, Zlotkowska D, Abramowicz P, Krupa-Kozak U. Daily oligofructose-enriched inulin intake impacts bone turnover markers but not the cytokine profile in pediatric patients with celiac disease on a gluten-free diet: Results of a randomised, placebo-controlled pilot study. Bone. 2019 May;122:184-192. doi: 10.1016/j.bone.2019.03.001. Epub 2019 Mar 3.
citation: Ferus K, Drabinska N, Krupa-Kozak U, Jarocka-Cyrta E. A Randomized, Placebo-Controlled, Pilot Clinical Trial to Evaluate the Effect of Supplementation with Prebiotic Synergy 1 on Iron Homeostasis in Children and Adolescents with Celiac Disease Treated with a Gluten-Free Diet. Nutrients. 2018 Nov 21;10(11):1818. doi: 10.3390/nu10111818.
citation: Drabinska N, Krupa-Kozak U, Abramowicz P, Jarocka-Cyrta E. Beneficial Effect of Oligofructose-Enriched Inulin on Vitamin D and E Status in Children with Celiac Disease on a Long-Term Gluten-Free Diet: A Preliminary Randomized, Placebo-Controlled Nutritional Intervention Study. Nutrients. 2018 Nov 15;10(11):1768. doi: 10.3390/nu10111768.
citation: Drabinska N, Krupa-Kozak U, Ciska E, Jarocka-Cyrta E. Plasma profile and urine excretion of amino acids in children with celiac disease on gluten-free diet after oligofructose-enriched inulin intervention: results of a randomised placebo-controlled pilot study. Amino Acids. 2018 Oct;50(10):1451-1460. doi: 10.1007/s00726-018-2622-7. Epub 2018 Jul 24.
citation: Drabinska N, Jarocka-Cyrta E, Markiewicz LH, Krupa-Kozak U. The Effect of Oligofructose-Enriched Inulin on Faecal Bacterial Counts and Microbiota-Associated Characteristics in Celiac Disease Children Following a Gluten-Free Diet: Results of a Randomized, Placebo-Controlled Trial. Nutrients. 2018 Feb 12;10(2):201. doi: 10.3390/nu10020201.
citation: Krupa-Kozak U, Drabinska N, Jarocka-Cyrta E. The effect of oligofructose-enriched inulin supplementation on gut microbiota, nutritional status and gastrointestinal symptoms in paediatric coeliac disease patients on a gluten-free diet: study protocol for a pilot randomized controlled trial. Nutr J. 2017 Aug 22;16(1):47. doi: 10.1186/s12937-017-0268-z.