Efficacy of Fermented Rice Flour for the Treatment of Atopic Dermatitis

Study Overview
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Brief Summary
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This Study Evaluate the efficacy of the subministration of fermented rice flour (7 g/day) on the clinical course of patients with moderate or severe Atopic Dermatitis, in terms of a reduction in the SCORAD score, during the study period and four weeks after the suspension of the treatment.

Detailed Description
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It is scientifically recognised that some probiotic effects can be obtained from inactivated bacteria or isolated bacterial components (e.g. bacterial DNA) or factors produced during fermentation (short-chain fatty acids, bacterial proteins, etc.) (7). This category also includes the ingredient which forms the focus of this trial: fermented rice flour, prepared from rice flour fermented by a probiotic (Lactobacillus paracasei CBA L74) which was heat-inactivated at the end of the fermentation process. The finished product, therefore, does not contain live bacteria. The bacterium used - owned by the sponsor and filed with the BCCM/LMG bacteria collection - belongs to the species Lactobacillus paracasei, and is included in the Qualified Presumption of Safety (QPS) list of microorganisms compiled by the European Food Safety Authority's Panel on Biological Hazards (8). The bacterium has been tested for its sensitivity to antibiotics on the basis of the relevant criteria drawn up by the EFSA (9) and its genomic sequence is known. Pre-clinical studies have shown anti-inflammatory effects of food matrices fermented with Lactobacillus paracasei CBA L74 (stimulating the production of IL-10 and the reduction of IL-12), and in response to stimulation with Salmonella typhimurium (10). Recently, the clinical effects of the consumption of rice flour fermented with Lactobacillus paracasei CBA L74 for 12 weeks were tested in a pilot study conducted on children with moderate/severe AD (defined using the SCORAD index) (11). In this study, all the children reported an improvement in the severity of the AD and reduced topical steroid application frequency. Considering the rationale for the use of live or inactivated probiotics or isolated bacterial components for the treatment of AD as well as the clinical studies in the paediatric population that have shown encouraging results (11), this randomised, double-blind, placebo-controlled trial aims to evaluate the efficacy of rice flour fermented with Lactobacillus paracasei CBA L74 in subjects with AD; in particular, this trial will evaluate the clinical response in terms of the severity of the AD during and at the end of a 12-week treatment period and four weeks after the suspension of the treatment.

Official Title
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Efficacy of Fermented Rice Flour for the Treatment of Atopic Dermatitis : Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Dietary Supplement: Rice Flour
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children between 6 and 36 months old, gradually enrolled from among patients attending the Paediatric Dermatology and Allergy Clinic Diagnosis of moderate or severe Atopic Dermatitis, evaluated using the SCORAD index Exclusion Criteria: Rhinitis and/or acute asthma Chronic diseases (autoimmune diseases, Cronic Obstructive Pulmunary Disease, heart disease, Congenital Nephrotic diseases, diabetes, acquired or congenital immunodeficiency) Treatment with prebiotics and/or probiotics in the month prior to enrolment Ongoing antibiotic therapy Treatment with systemic immunomodulators in the month prior to enrolment Treatment with topical immunomodulators (tacrolimus or pimecrolimus) in the three months prior to enrolment

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Group will receive 7gr Maltodextrin | Dietary Supplement: Placebo<br>* For 12 weeks a group of children will receive a 7gr of a placebo (maltodextrin), according to a randomised, double-blind design.<br>|
| Experimental: Intervention Rice Flour<br>The Intervention Group will receive 7gr of the experimental ingredient fermented Rice Flour | Dietary Supplement: Rice Flour<br>* For 12 weeks, a group of children will receive 7gr fermented rice flour according to a randomised, double-blind design.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in the SCORAD score | Standardised questionnaire for calculating the SCORAD score: Evaluate the efficacy of the administration of fermented rice flour (7 g/day) on the clinical course of patients with moderate or severe Atopic Dermatitis, in terms of a reduction in the SCORAD score, during the study period and four weeks after the suspension of the treatment | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory response :Peripheral immunophenotype analysis and Cytokine profile | Evaluate the inflammatory response at baseline (T0) and at the end of treatment (T12) in terms of inflammation markers (cytokine profile) and peripheral immunophenotype compared to the placebo group.Peripheral cytokine assay (IFNγ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-18, IL-31) at baseline and after specific stimulation (anti-CD3/CD28) or non-specific stimulation (PHA) on all enrolled children. | 12 weeks | 
| Allergic sensitisation:Total and specific IgE (sIgE) assay | Evaluate allergic sensitisation by total and specific IgE (sIgE) assay at baseline (T0) and at the end of treatment (T12) compared to the placebo group | 12 weeks | 
| Steroids prescription | Evaluate the prescription of topical steroid therapy in the group of children treated with fermented rice flour compared to the placebo group. | 16 weeks | 
| Faecal microbiota analysis | Evaluate the change in intestinal microbial flora between T0 and T12 | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lactobacillus, Probiotics