Prevention of Celiac Disease in Skåne

Study Overview
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Brief Summary
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This study aims to investigate the impact on being on a gluten free diet the first three years of life compared to a daily intake of a probiotic supplementation or placebo on the risk of developing celiac disease autoimmunity or celiac disease in genetically susceptible children. Study participants will be randomly allocated to one of the three study groups before the age of 4 months and will remain in that group with the corresponding intervention during the three first years of life. Regular visits to a study nurse and contact with study dietician will be scheduled. The dietician will support the families in keeping the correct diet intended for each study group.

Detailed Description
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The primary hypothesis to be tested is that a strictly gluten free diet during the first three years of life with a slow introduction of gluten during the follow-up period will induce tolerance to gluten. A similar hypothesis is tested if a daily supply of two different lactobacillus (LB) strains can suppress an inflammatory response to gluten in the intestine by stimulating regulatory T-cells and reduced permeability of gluten peptides in the intestine. The secondary hypothesis tested is that celiac disease can not be prevented, but the onset of the disease will be delayed in children returning to a gluten-containing diet after the intervention period (gluten free diet) or probiotic treatment) during the first three years of life. The intervention period is 3 years and the follow-up period is further 4 years. The primary aim is to study the proportion of children who develop celiac disease autoimmunity and progression to celiac disease by the age of 3 years. Secondary aim is to study the proportion of children who developed celiac disease at the age of 7 years.

Official Title
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Prevention of Celiac Disease in Skåne (in Swedish - Prevention av Celiaki i Skåne)

Conditions
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Celiac Disease in Children

Intervention / Treatment
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* Other: Gluten free diet
* Dietary Supplement: Probiotics
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children screened positive for human leucocyte antigen (HLA) DR3-DQ2/DR3-DQ2 Children must be enrolled to the study by 4 months of age (before gluten consumption has started). Exclusion Criteria: Congenital chronic disorder where intervention with diet or probiotics may be affected. Written consent from both caregivers are missing

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 4 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gluten free diet<br>Gluten free diet | Other: Gluten free diet<br>* Controlled gluten free diet<br>|
| Active Comparator: Probiotics<br>Capsules with a combination of two probiotic bacteria with maize starch as excipient and at a total dose of 10(10) colony forming units (CFU)/capsule. | Dietary Supplement: Probiotics<br>* Capsules<br>|
| Placebo Comparator: Placebo<br>Placebo capsules with maize starch and without any bacteria. | Dietary Supplement: Placebo<br>* Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of children tested positive for persistent tissue transglutaminase (tTG) autoantibodies, defined as celiac disease autoimmunity | Radioligand binding assays (RBA) will be used to measure tTG autoantibodies in serum samples collected every third months up until the age of 3 years and then annually up until the age of 7 years. | from 4 months of age up until 7 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of children diagnosed with celiac disease | A celiac disease diagnose will be defined by an intestinal biopsy showing a Marsh score of 2 or higher or by high levels of tTG autoantibodies (> 100 units) in at least 2 consecutive blood samples. | Up until 7 years of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coeliac disease, celiac disease autoimmunity