Clinical trial NCT00378300: The Effects of Probiotics in Atopic Dermatitis
Official title: Probiotics Ameliorate Atopic Dermatitis by Induction of T Regulatory Cells
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
Probiotics
T Regulatory Cells
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2006-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to study the clinical effects of taking probiotics in patients who have moderate to severe atopic dermatitis. There has been several studies showing improvement in the severity of atopic dermatitis after taking probiotics. The mechanism of this improvement is currently unknown. We propose that probiotics improve atopic dermatitis by stimulating, or increasing, the activity of a special type of cell called the T Regulatory cell--which can suppress the activity of allergic disease.

Detailed description: The central hypothesis of this study is that a subset of commercially available probiotic formulations will ameliorate moderate to severe atopic dermatitis in children by inducing the development of T Regulatory (Treg) cells. We specifically hypothesize that the probiotic mixture that induces Treg activity in vitro, will also improve the severity of atopic dermatitis in a specific patient by inducing Treg activity in vivo.

1. We will determine whether probiotic mixtures are better able to ameliorate the severity of atopic dermatitis when compared to patients treated with placebo. We will conduct a 4-week randomized, double-blind, placebo controlled clinical trial designed to evaluate the efficacy of probiotics in reducing the clinical severity of atopic dermatitis as assessed by our primary outcome measure, the SCORing Atopic Dermatitis (SCORAD) index. We specifically hypothesize that probiotics will clinically improve the disease.
2. We will assess whether probiotic mixtures induce the development of T regulatory cells in patients with atopic dermatitis.

A. We will measure the relative levels of Tregs in peripheral blood before and after probiotic or placebo administration in order to assess whether the probiotic mixtures alter Treg development in vivo, and whether these changes correlate with improvement in clinical scores. Primary outcomes will be measurements of gene expression and absolute increases in cell population. We specifically hypothesize that probiotics will increase Treg activity.

B. We will also determine if all patients' Tregs have in vitro responses to probiotics. This data will be used to correlate whether clinical responders in the study also have strong in vitro responses.

Eligibility criteria: Inclusion Criteria:

* Age between 6 months to 3 years
* Physician diagnosis of moderate to severe atopic dermatitis as defined by the Hanifin and Rajka criteria
* Ability to take enterally commercially available probiotics by powder form added to food or drink
* Ability to undergo venipuncture or dermal puncture (if less than 1 year old)

Exclusion Criteria:

* Prior exposure to probiotics
* Current antibiotic administration
* Known history of chronic medical condition such as congenital heart disease, liver or kidney disease, or immune deficiency
* Absence of T regulatory cell induction by probiotic bacteria on initial laboratory assessment
* Any other condition in which the Investigators involved in the study determine potential subject is unsuitable for the study

Primary outcomes:
measure: SCORAD Score change taken at baseline and after 1 month of either probiotic or placebo
measure: T Regulatory cell activity change taken at baseline and after 1 month of either probiotic or placebo
Secondary outcomes:
measure: Dermatitis Family Impact Questionnaire change taken at baseline and after 1 month of either probiotic or placebo
measure: T Regulatory cell activity when exposed to probiotics in vitro
measure: Change in Serum IgE or IgG levels taken at baseline and after 1 month of either probiotic or placebo
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Michael H Land, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Martin G Martin, MD, MPP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Robert L Roberts, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Tatiana Hernandez
role: STUDY_DIRECTOR
References:
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citation: Pessi T, Sutas Y, Hurme M, Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000 Dec;30(12):1804-8. doi: 10.1046/j.1365-2222.2000.00948.x.
citation: Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71. doi: 10.1016/S0140-6736(03)13490-3.
citation: Rosenfeldt V, Benfeldt E, Nielsen SD, Michaelsen KF, Jeppesen DL, Valerius NH, Paerregaard A. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol. 2003 Feb;111(2):389-95. doi: 10.1067/mai.2003.389.
citation: Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child. 2005 Sep;90(9):892-7. doi: 10.1136/adc.2004.060673. Epub 2005 Apr 29.
citation: Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M. Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy. 2005 Apr;60(4):494-500. doi: 10.1111/j.1398-9995.2004.00514.x.
citation: Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, van Capel TM, Zaat BA, Yazdanbakhsh M, Wierenga EA, van Kooyk Y, Kapsenberg ML. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005 Jun;115(6):1260-7. doi: 10.1016/j.jaci.2005.03.036.