Clinical trial NCT01494142: Registry for the Atopic Dermatitis Research Network
Official title: Registry for the Atopic Dermatitis Research Network (ADRN-02)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atopic Dermatitis
Eczema Herpeticum
Keywords: Registry
Atopic Dermatitis
Eczema Herpeticum
GWAS
Staphylococcus aureus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Atopic Dermatitis Research Network
First posted: 2011-12-16
Enrollment: 3387
Sex: ALL
Minimum age (years): 8
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A minimum of 1100 ADEH-Staph+ participants and a minimum of 1100 ADEH-Staph- participants 3-80 years of age will be enrolled. In addition, ADEH+, ADEV+, and Non-atopic participants 8 months to 80 years of age will be enrolled.

It is unknown whether Staph colonization status will change as younger participants get older. For this reason, the lower age limit for inclusion of ADEH- participants is 3 years rather than 8 months to ensure that characterization of their Staph+ vs. Staph- state is more accurate

Brief summary: The purpose of this multi-center, clinical registry study is to determine genetic markers associated with susceptibility of AD patients to infections and to also serve as a potential participant database for future studies.

Detailed description: People with atopic dermatitis (AD), also known as eczema, experience hot, dry, scaly skin with severe itching. In addition, people with AD are prone to skin infections and inflammation. Little is known about the causes of AD or why people with AD are more prone to infections. The purpose of this multi-center, clinical registry study is to determine genetic markers associated with susceptibility of AD patients to infections and to also serve as a potential participant database for future studies.

Study procedures will usually be completed in one visit to the clinic; however, participants may need to return for one or more additional visits to provide blood and skin swabs if they do not meet sampling criteria at the initial Screening Visit. A subset of participants from National Jewish Health may be asked to return to clinic for 2 additional visits approximately 7 and 14 days after the original sample collection for collection of skin swabs for assessment of antimicrobial activity. All participants may also be asked to return for an Unscheduled Visit to provide additional blood and/or skin swabs. Atopic Dermatitis with previous or current Eczema Herpeticum (ADEH+), Atopic Dermatitis with previous or current Eczema Vaccinatum (ADEV+) and Methicillin-Resistant S. Aureus (MRSA+) participants will be contacted every 6 months for the duration of the study.

Recruitment emphasis will include Non-Hispanic Caucasian, Non-Hispanic African American, and Mexican American since these constitute the three largest racial/ethnic populations according to the U.S. Census Bureau 2009 data; however, no racial/ethnic groups will be excluded. Our scientific rationale for targeting these three racial/ethnic groups is to ensure that we are able to recruit sufficient numbers of participants in each group to perform meaningful tests for genetic association.

Eligibility criteria: Inclusion Criteria:

Participants who meet all of the following criteria are eligible for enrollment. Participants may be reassessed if not initially eligible.

* ADEH+ and Non-atopic males and females ages 8 months to 80 years, inclusive, at the time of Enrollment, and ADEH- males and females ages 3 years to 80 years, inclusive, at the time of Enrollment.
* Who are willing to sign the informed consent form or whose parent or legal guardian is willing to sign the informed consent form (age appropriate) prior to initiation of any study procedures.
* Who are willing to sign the assent form, if age appropriate.
* Who meet criteria for one of the diagnostic groups (ADEH-Staph+, ADEH-Staph-, ADEH+, ADEV+, Non-atopic) as defined in the ADRN Standard Diagnostic Criteria and the Staphylococcus aureus Colonization Criteria.

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for enrollment.

* Who have an active systemic malignancy; uncomplicated non-melanoma skin cancer and melanoma in situ with documentation of complete excision are not exclusionary.
* Who have any skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous diseases, psoriasis, cutaneous T cell lymphoma \[also called Mycosis Fungoides or Sezary syndrome\], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease).
* Who have a history of systemic immunological illness (e.g., immunodeficiency disorders such as human immunodeficiency virus \[HIV\] or lupus erythematosus) other than the condition being studied.
* Who have a first degree relative already enrolled in the study.
* Who are determined not to be eligible in the opinion of the Investigator.

Primary outcomes:
measure: Genotype and sequence data from ADEH+ and ADEH- participants.
timeFrame: Day 1
measure: Genotype and sequence data from ADEH- participants with and without bacterial colonization with S. aureus.
timeFrame: Day 1
Secondary outcomes:
measure: Single Nucleotide Polymorphism (SNP) and Copy Number Variant (CNV) genotype data for candidate genes, including but not limited to Claudin-1 (CLDN1) and Filaggrin (FLG).
timeFrame: Day 1
measure: SNP genotype data for candidate genes, including but not limited to CLDN1 and FLG, validated in samples from an independent AD population.
timeFrame: Day 1
measure: Targeted deep resequencing of candidate genes, including but not limited to CLDN1.
timeFrame: Day 1
measure: Analysis of S. aureus isolates for antibiotic sensitivity
timeFrame: Day 1
measure: Analysis of S. aureus isolates for staphylococcal cassette chromosome (SCC) mec DNA elements.
timeFrame: Day 1
measure: Analysis of S. aureus isolates for expression of virulence or other factors.
timeFrame: Day 1
measure: Expression of biomarkers, including but not limited to serum biomarkers, among AD sub-phenotypes.
timeFrame: Day 1
measure: Analysis of microbial composition by 16S ribosomal Deoxyribonucleic Acid (rDNA) amplicon sequencing.
timeFrame: Day 1
measure: Analysis of DNA methylation profiles
timeFrame: Day 1
measure: Analysis of messenger Ribonucleic Acid (mRNA) expression profiles in whole blood samples.
timeFrame: Day 1
measure: Frequency of commensal Staphylococcus species producing antimicrobial activity
timeFrame: Day 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: University of Rochester
name: Lisa Beck, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins Asthma and Allergy Center
name: Kathleen Barnes, PhD
role: STUDY_CHAIR
References:
citation: Gao L, Bin L, Rafaels NM, Huang L, Potee J, Ruczinski I, Beaty TH, Paller AS, Schneider LC, Gallo R, Hanifin JM, Beck LA, Geha RS, Mathias RA, Barnes KC, Leung DYM. Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2015 Dec;136(6):1591-1600. doi: 10.1016/j.jaci.2015.06.047. Epub 2015 Sep 3.
citation: Shi B, Bangayan NJ, Curd E, Taylor PA, Gallo RL, Leung DYM, Li H. The skin microbiome is different in pediatric versus adult atopic dermatitis. J Allergy Clin Immunol. 2016 Oct;138(4):1233-1236. doi: 10.1016/j.jaci.2016.04.053. Epub 2016 Jun 29. No abstract available.
citation: Nakatsuji T, Chen TH, Two AM, Chun KA, Narala S, Geha RS, Hata TR, Gallo RL. Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. J Invest Dermatol. 2016 Nov;136(11):2192-2200. doi: 10.1016/j.jid.2016.05.127. Epub 2016 Jul 2.
citation: Merriman JA, Mueller EA, Cahill MP, Beck LA, Paller AS, Hanifin JM, Ong PY, Schneider L, Babineau DC, David G, Lockhart A, Artis K, Leung DY, Schlievert PM. Temporal and Racial Differences Associated with Atopic Dermatitis Staphylococcusaureus and Encoded Virulence Factors. mSphere. 2016 Dec 7;1(6):e00295-16. doi: 10.1128/mSphere.00295-16. eCollection 2016 Nov-Dec.
citation: Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, Shafiq F, Kotol PF, Bouslimani A, Melnik AV, Latif H, Kim JN, Lockhart A, Artis K, David G, Taylor P, Streib J, Dorrestein PC, Grier A, Gill SR, Zengler K, Hata TR, Leung DY, Gallo RL. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med. 2017 Feb 22;9(378):eaah4680. doi: 10.1126/scitranslmed.aah4680.