Registry for the Atopic Dermatitis Research Network

Registry for the Atopic Dermatitis Research Network (ADRN-02)

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 Overview

• Status: Completed
• Conditions: Atopic Dermatitis; Eczema Herpeticum

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.

• Study Type: Observational
• Enrollment (Actual): 3387

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60614
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
ADEH-Staph+; Atopic Dermatitis without a history of Eczema Herpeticum and with S. aureus skin colonization. A minimum of 1100 participants will be enrolled; we will target 500 Non-Hispanic Caucasian, 300 Non-Hispanic African American, and 300 Mexican American Caucasian ADEH-Staph+ participants. Although we will target these three groups, no racial/ethnic groups will be excluded.
ADEH-Staph-; Atopic Dermatitis without a history of Eczema Herpeticum and without S. aureus skin colonization. A minimum of 1100 participants will be enrolled; we will target 500 Non-Hispanic Caucasian, 300 Non-Hispanic African American, and 300 Mexican American Caucasian ADEH-Staph- participants. Although we will target these three groups, no racial/ethnic groups will be excluded.
ADEH+; Atopic Dermatitis with previous or current Eczema Herpeticum.We will try to include a minimum of 150 Non-Hispanic Caucasian ADEH+ participants. ADEH+ participants of other racial/ethnic groups will not be excluded
ADEV+; Atopic Dermatitis with previous or current Eczema Vaccinatum. ADEV+ sub-phenotype is very rare so all eligible participants will be enrolled.
Non-atopic; Non-atopic healthy participants. A minimum of 250 non-atopic participants will be enrolled. Non-atopic participants will serve as a control group for the genetic, biomarker, Staph characterization, and microbiome studies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Genotype and sequence data from ADEH+ and ADEH- participants.	Day 1
Genotype and sequence data from ADEH- participants with and without bacterial colonization with S. aureus.	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
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).	Day 1
SNP genotype data for candidate genes, including but not limited to CLDN1 and FLG, validated in samples from an independent AD population.	Day 1
Targeted deep resequencing of candidate genes, including but not limited to CLDN1.	Day 1
Analysis of S. aureus isolates for antibiotic sensitivity	Day 1
Analysis of S. aureus isolates for staphylococcal cassette chromosome (SCC) mec DNA elements.	Day 1
Analysis of S. aureus isolates for expression of virulence or other factors.	Day 1
Expression of biomarkers, including but not limited to serum biomarkers, among AD sub-phenotypes.	Day 1
Analysis of microbial composition by 16S ribosomal Deoxyribonucleic Acid (rDNA) amplicon sequencing.	Day 1
Analysis of DNA methylation profiles	Day 1
Analysis of messenger Ribonucleic Acid (mRNA) expression profiles in whole blood samples.	Day 1
Frequency of commensal Staphylococcus species producing antimicrobial activity	Day 1

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Atopic Dermatitis Research Network
• Investigators: Study Chair: Lisa Beck, MD, University of Rochester; Study Chair: Kathleen Barnes, PhD, Johns Hopkins Asthma and Allergy Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Atopic Dermatitis Research Network (ADRN)

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 7, 2018
• Study Completion (Actual): February 7, 2018

Study Registration Dates

• First Submitted: October 31, 2011
• First Submitted That Met QC Criteria: December 14, 2011
• First Posted (Estimate): December 16, 2011

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; Registry; Atopic Dermatitis; GWAS; Eczema Herpeticum
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; DNA Virus Infections; Skin Diseases, Genetic; Skin Diseases, Infectious; Hypersensitivity; Skin Diseases, Viral; Skin Diseases, Eczematous; Herpesviridae Infections; Herpes Simplex; Dermatitis; Eczema; Dermatitis, Atopic; Kaposi Varicelliform Eruption
• Other Study ID Numbers: DAIT ADRN-02