Probiotic Lactobacillus Rhamnosus GG for Pediatric Atopic Dermatitis (PROPAD)

The Use of Probiotic Lactobacillus Rhamnosus GG for Treatment of Atopic Dermatitis in Children

Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder that results in areas of dry, itchy skin. AD affects up to 20% of children in Western societies and represents a prevalent, burdensome, and psychologically important pediatric concern.

It often appears in infancy and may persist into adolescence and adulthood. This complex disease is typified by defective skin barrier function with activation of abnormal immunological and inflammatory pathways upon exposure to ubiquitous environmental allergens.

It often appears in infancy and may persist into adolescence and adulthood. This complex disease is typified by defective skin barrier function with activation of abnormal immunological and inflammatory pathways upon exposure to ubiquitous environmental allergens.

This complex disease is typified by defective skin barrier function with activation of abnormal immunological and inflammatory pathways upon exposure to ubiquitous environmental allergens. This phenomenon may be primarily related to mutations in important barrier proteins, in the same fashion as filaggrin in the atopic skin, or may be secondary, reflecting the intestinal mucosal damage caused by local hypersensitivity reactions to food antigens or to microbial components as in inflammatory bowel disease. Conventional therapy for AD consists of elimination of exacerbating factors, moisturizers to maintain skin hydration, antihistamines to alleviate pruritus, topically applied corticosteroids, or topical calcineurin inhibitors to control inflammation. Severe forms of atopic dermatitis may need systemic corticosteroids, oral cyclosporine, and/or phototherapy.

Probiotics have been suggested as a novel treatment approach for atopic dermatitis. Specific probiotics have been shown to normalize intestinal permeability, to counteract intestinal immune dysfunction and to normalize gut dysbiosis. Hence, their clinical benefit may reside in the control of gut inflammation induced by various intraluminal antigens and enhancement of adaptive and especially innate immune responses.

Indeed, above and beyond balancing the gut microecology and promoting host immune defences, specific probiotics might further aid in controlling the microbial colonization of the skin, thereby reducing proneness to secondary infections which typically cause sustained symptoms. However, there are conflicting evidence on the utility of selected probiotic strains for atopic dermatitis, and major problems are due to dose and viability of strain used, duration of treatment, study population.

The aim of this randomized, double-blind, placebo-controlled study is to evaluate the efficacy of the most studied probiotic in the pediatric allergy field - Lactobacillus rhamnosus GG (LGG) - in children affected by atopic dermatitis.

Study Overview

• Status: Unknown
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Other: placebo; Dietary supplement: Lactobacillus rhamnosus GG

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • University of Naples Federico II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children aged 6-36 months
• diagnosis of Atopic Dermatitis according to SCORAD index

Exclusion Criteria

• Age < 6 months
• age > 36 months,
• skin infections,
• ichthyosis,
• food allergies,
• other allergic diseases,
• chronic systemic diseases,
• congenital cardiac defects,
• active tuberculosis,
• autoimmune diseases,
• immunodeficiency,
• chronic inflammatory bowel diseases,
• celiac disease,
• cystic fibrosis,
• metabolic diseases,
• malignancy,
• chronic pulmonary diseases,
• malformations of the gastrointestinal and/or respiratory tract,
• administration of prebiotics/ probiotics/symbiotic/systemic immunomodulators during the 4 weeks before enrolment,
• treatments with topical immunomodulators (Tacrolimus or Pimecrolimus) over the three months prior to enrolment;
• use of corticosteroids or calcineurin antagonists or phototherapy in the previous 4 weeks,
• use of systemic antibiotics or anti-mycotic drugs during 4 weeks before study entry;
• investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements;
• participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study;
• hypersensitivity to components contained in study product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; maltodextrin	Other: placebo; placebo
Experimental: Lactobacillus rhamnosus GG; Lactobacillus rhamnosus GG (10 billion Colony Forming Units/CAPSULE)	Dietary supplement: Lactobacillus rhamnosus GG; PROBIOTIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of SCORing Atopic Dermatitis (SCORAD)	The efficacy of LGG supplementation on clinical course of children in terms of reduction of SCORAD index (score minimum 0 - maximum 60)	after 12-week treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of gut microbiota	gut microbiota metagenomic in term of total genomic DNA	after 12-week treatment
Composition of gut microbiota metabolomic feature	Determination of short chain fatty acids	after 12-week treatment
evaluation acquired immunity	evaluation acquired immunity by determining fecal Immunoglobulin A levels	after 12-week treatment
evaluation of quality of life	evaluation of Infant Dermatitis Quality of Life Questionnaire (IDQOL) (score minimum 0 - maximum 30)	after 12-week treatment

Collaborators and Investigators

• Sponsor: Federico II University

Publications and helpful links

General Publications

• Carucci L, Nocerino R, Paparo L, De Filippis F, Coppola S, Giglio V, Cozzolino T, Valentino V, Sequino G, Bedogni G, Russo R, Ercolini D, Berni Canani R. Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial. Pediatr Allergy Immunol. 2022 Aug;33(8):e13836. doi: 10.1111/pai.13836.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 15, 2019
• Primary Completion (Anticipated): May 15, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: March 3, 2019
• First Submitted That Met QC Criteria: March 3, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 400/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No