<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03038932</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT ADRN-06</org_study_id>
    <nct_id>NCT03038932</nct_id>
  </id_info>
  <brief_title>Etiology of Eczema Herpeticum (EH)</brief_title>
  <official_title>Integrated Extreme Trait Analysis to Understand the Etiology of Eczema Herpeticum (ADRN-06)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Atopic Dermatitis Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rho Federal Systems Division, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Atopic dermatitis, also called eczema, is a disease with dry, scaly, itchy skin. Those with&#xD;
      atopic dermatitis may have complications from skin infections such as eczema herpeticum after&#xD;
      herpes simplex virus (HSV) infection. Symptoms of eczema herpeticum include fever and&#xD;
      clusters of itchy blisters which crust over and form sores. Although exposure to HSV is&#xD;
      widespread, most people clear the virus and only a subset of individuals with atopic&#xD;
      dermatitis develop eczema herpeticum.&#xD;
&#xD;
      The purpose of this study is to determine why some individuals with atopic dermatitis are at&#xD;
      higher risk for recurrent skin infections with HSV. The study team will compare how people&#xD;
      with atopic dermatitis with a history of recurrent eczema herpeticum, people with atopic&#xD;
      dermatitis without a history of eczema herpeticum, and people without atopic dermatitis&#xD;
      respond to HSV.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study uses whole genome sequencing (WGS) technology to identify genetic variants that&#xD;
      confer risk of recurrent atopic dermatitis with a history of eczema herpeticum (ADEH+), with&#xD;
      ≥3 eczema herpeticum (EH) episodes.&#xD;
&#xD;
      A small subgroup of individuals with atopic dermatitis (AD) suffer from life-threatening&#xD;
      disseminated herpes simplex virus (HSV) skin infections, termed eczema herpeticum (ADEH+).&#xD;
      The manifestation of ADEH+ however is not simply a consequence of herpes simplex virus type 1&#xD;
      (HSV-1) infections, since the majority of the US population is latently infected with HSV-1&#xD;
      from an early age. Most importantly, there is a bimodality in the recurrence of eczema&#xD;
      herpeticum (EH) episodes; most individuals have only a single episode but a subgroup of ADEH+&#xD;
      individuals has 3 or more episodes.&#xD;
&#xD;
      This study aims to conduct an extreme trait investigation of ADEH+ with recurrent EH, ≥3&#xD;
      episodes, compared to AD without a history of eczema herpeticum (ADEH-), using whole genome&#xD;
      sequencing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 22, 2017</start_date>
  <completion_date type="Actual">November 24, 2020</completion_date>
  <primary_completion_date type="Actual">November 24, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The Difference in Frequency of Rare Deleterious Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing</measure>
    <time_frame>3 years</time_frame>
    <description>Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious coding genetic variants between recurrent Atopic Dermatitis (AD) subjects with a history of Eczema Herpeticum (ADEH+) and ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Difference in Frequency of Rare Deleterious Non-Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing</measure>
    <time_frame>3 years</time_frame>
    <description>Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious non-coding genetic variants between subjects with recurrent Atopic Dermatitis (AD) subjects and a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in the dermis</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in the epidermis</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in in keratinocytes</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in fibroblasts</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression profiles in skin tape strip samples</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Herpes Simplex Virus (HSV) replication in primary keratinocytes</measure>
    <time_frame>3 years</time_frame>
    <description>HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Herpes Simplex Virus (HSV) replication in fibroblasts</measure>
    <time_frame>3 years</time_frame>
    <description>HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)</measure>
    <time_frame>3 years</time_frame>
    <description>HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Herpes Simplex Virus (HSV) replication in genetically modified cell lines</measure>
    <time_frame>3 years</time_frame>
    <description>HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-viral responses in primary keratinocytes</measure>
    <time_frame>3 years</time_frame>
    <description>Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-viral responses in fibroblasts</measure>
    <time_frame>3 years</time_frame>
    <description>Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)</measure>
    <time_frame>3 years</time_frame>
    <description>Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-viral responses in genetically modified cell lines</measure>
    <time_frame>3 years</time_frame>
    <description>Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune responses in primary keratinocytes</measure>
    <time_frame>3 years</time_frame>
    <description>Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune responses in fibroblasts</measure>
    <time_frame>3 years</time_frame>
    <description>Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune responses in Plasmacytoid Dendritic Cells (pDCs)</measure>
    <time_frame>3 years</time_frame>
    <description>Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune responses in genetically modified cell lines</measure>
    <time_frame>3 years</time_frame>
    <description>Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differentiation markers in primary keratinocytes</measure>
    <time_frame>3 years</time_frame>
    <description>Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differentiation markers in genetically modified keratinocyte cell lines</measure>
    <time_frame>3 years</time_frame>
    <description>Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of reporter gene constructs testing non-coding variants</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Viral carriage</measure>
    <time_frame>3 years</time_frame>
    <description>Viral carriage will be assessed by presence of viral sequencing reads.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Protein expression of epidermal differentiation complex</measure>
    <time_frame>3 years</time_frame>
    <description>Protein expression of epidermal differentiation complex will be measured by Mass Spectroscopy of skin tape strips.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Protein expression of inflammatory genes</measure>
    <time_frame>3 years</time_frame>
    <description>Protein expression of inflammatory genes will be measured by Mass Spectroscopy of skin tape strips.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Lipid profiles</measure>
    <time_frame>3 years</time_frame>
    <description>Lipid profiles will be measured by mass spectroscopy of skin tape strips.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Whole-genome DNA methylation profiles from epidermis</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory: Whole-genome DNA methylation profiles from dermis</measure>
    <time_frame>3 Years</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">69</enrollment>
  <condition>Eczema Herpeticum</condition>
  <arm_group>
    <arm_group_label>Discovery Cohort</arm_group_label>
    <description>A minimum of 50 recurrent Atopic Dermatitis with a history of Eczema Herpeticum(ADEH+), 500 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-), and 237 Non-Atopic (NA) European American participants from the Atopic Dermatitis Research Network (ADRN) DNA Repository.&#xD;
The study will learn from this cohort:&#xD;
All Single Nucleotide Variants (SNVs) in ADEH+&#xD;
ADEH+ specific deleterious SNVs&#xD;
The study will determine the function of:&#xD;
4. ADEH+ risk variants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Independent populations of participants</arm_group_label>
    <description>Two independent populations of participants:&#xD;
Children, aged 3-17 years and&#xD;
Adults 18-64 years of age.&#xD;
A minimum of 12 recurrent Atopic Dermatitis with a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, 12 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-) and 12 Non-Atopic (NA) participants will be enrolled in each of the two populations.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood and Skin Tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A minimum of 50 recurrent Atopic Dermatitis with a history of Eczema Herpeticum(ADEH+), 500&#xD;
        Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-), and 237 Non-Atopic (NA)&#xD;
        European American participants from the Atopic Dermatitis Research Network (ADRN) DNA&#xD;
        Repository. The protocol will also enroll two independent populations of participants 1)&#xD;
        children, 3-17 years of age and 2) adults 18-64 years of age. A minimum of 12 recurrent&#xD;
        ADEH+ with ≥3 EH episodes, 12 ADEH- and 12 NA participants will be enrolled in each of the&#xD;
        two populations.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must be a participant already enrolled in the ADRN Registry and provided DNA&#xD;
             (ClinicalTrials.gov ID: NCT01494142);&#xD;
&#xD;
          2. Participant and/or parent guardian must be able to understand and provide informed&#xD;
             consent;&#xD;
&#xD;
          3. A history of Atopic Dermatitis (AD) with a history of eczema herpeticum (ADEH+), as&#xD;
             diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic&#xD;
             Criteria, with ≥3 episodes of Eczema Herpeticum (EH)&#xD;
&#xD;
             OR&#xD;
&#xD;
             A history of AD without a history of eczema herpeticum (ADEH-), as diagnosed using the&#xD;
             ADRN Standard Diagnostic Criteria, and no immediate family members (mother, father,&#xD;
             full siblings, half-siblings, offspring, aunts, uncles, cousins, or grandparents) with&#xD;
             a history of EH&#xD;
&#xD;
             OR&#xD;
&#xD;
             Non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria.&#xD;
&#xD;
          4. Anti-Herpes Simplex Virus (HSV)-1 or Anti-HSV-2 Immunoglobulin G (IgG) seropositive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability or unwillingness of a participant and/or parent guardian to give written&#xD;
             informed consent or comply with study protocol;&#xD;
&#xD;
          2. Pregnant or lactating women;&#xD;
&#xD;
          3. Known or suspected immunosuppression;&#xD;
&#xD;
          4. Severe concomitant illness(es);&#xD;
&#xD;
          5. History of keloid formation (adults only);&#xD;
&#xD;
          6. History of lidocaine or Novocain allergy (adults only);&#xD;
&#xD;
          7. History of serious life-threatening reaction to latex, tape, or adhesives;&#xD;
&#xD;
          8. Past or current medical problems or findings from physical examination or laboratory&#xD;
             testing that are not listed above, which, in the opinion of the investigator, may pose&#xD;
             additional risks from participation in the study, may interfere with the participant's&#xD;
             ability to comply with study requirements or that may impact the quality or&#xD;
             interpretation of the data obtained from the study.&#xD;
&#xD;
          9. Use of biologics within 5 half-lives (if known) or 16 weeks of the Screening Visit;&#xD;
&#xD;
         10. Use of an investigational drug within 5 half-lives (if known) or 8 weeks of the&#xD;
             Screening Visit.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Donald Leung, M.D., Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>National Jewish Health: Division of Pediatric Allergy and Clinical Immunology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Jewish Health: Division of Pediatric Allergy and Clinical Immunology</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.gov/ct2/show/NCT01494142</url>
    <description>ClinicalTrials.gov Record for Atopic Dermatitis Research Network Registry</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID) website</description>
  </link>
  <link>
    <url>https://www.niaid.nih.gov/research/atopic-dermatitis-research-network</url>
    <description>Atopic Dermatitis Research Network (ADRN) information</description>
  </link>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>January 13, 2021</last_update_submitted>
  <last_update_submitted_qc>January 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>whole genome sequencing (WGS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kaposi Varicelliform Eruption</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03038932
org study id: DAIT ADRN-06
nct id: NCT03038932
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Atopic dermatitis, also called eczema, is a disease with dry, scaly, itchy skin. Those with
      atopic dermatitis may have complications from skin infections such as eczema herpeticum after
      herpes simplex virus (HSV) infection. Symptoms of eczema herpeticum include fever and
      clusters of itchy blisters which crust over and form sores. Although exposure to HSV is
      widespread, most people clear the virus and only a subset of individuals with atopic
      dermatitis develop eczema herpeticum.

      The purpose of this study is to determine why some individuals with atopic dermatitis are at
      higher risk for recurrent skin infections with HSV. The study team will compare how people
      with atopic dermatitis with a history of recurrent eczema herpeticum, people with atopic
      dermatitis without a history of eczema herpeticum, and people without atopic dermatitis
      respond to HSV.
This study uses whole genome sequencing (WGS) technology to identify genetic variants that
      confer risk of recurrent atopic dermatitis with a history of eczema herpeticum (ADEH+), with
      ≥3 eczema herpeticum (EH) episodes.

      A small subgroup of individuals with atopic dermatitis (AD) suffer from life-threatening
      disseminated herpes simplex virus (HSV) skin infections, termed eczema herpeticum (ADEH+).
      The manifestation of ADEH+ however is not simply a consequence of herpes simplex virus type 1
      (HSV-1) infections, since the majority of the US population is latently infected with HSV-1
      from an early age. Most importantly, there is a bimodality in the recurrence of eczema
      herpeticum (EH) episodes; most individuals have only a single episode but a subgroup of ADEH+
      individuals has 3 or more episodes.

      This study aims to conduct an extreme trait investigation of ADEH+ with recurrent EH, ≥3
      episodes, compared to AD without a history of eczema herpeticum (ADEH-), using whole genome
      sequencing.
observational model: Case-Control
time perspective: Prospective
measure: The Difference in Frequency of Rare Deleterious Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing
time frame: 3 years
description: Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious coding genetic variants between recurrent Atopic Dermatitis (AD) subjects with a history of Eczema Herpeticum (ADEH+) and ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.
measure: The Difference in Frequency of Rare Deleterious Non-Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing
time frame: 3 years
description: Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious non-coding genetic variants between subjects with recurrent Atopic Dermatitis (AD) subjects and a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.
measure: Gene expression profiles in the dermis
time frame: 3 years
measure: Gene expression profiles in the epidermis
time frame: 3 years
measure: Gene expression profiles in in keratinocytes
time frame: 3 years
measure: Gene expression profiles in fibroblasts
time frame: 3 years
measure: Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)
time frame: 3 years
measure: Gene expression profiles in skin tape strip samples
time frame: 3 years
measure: Herpes Simplex Virus (HSV) replication in primary keratinocytes
time frame: 3 years
description: HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
measure: Herpes Simplex Virus (HSV) replication in fibroblasts
time frame: 3 years
description: HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
measure: Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)
time frame: 3 years
description: HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
measure: Herpes Simplex Virus (HSV) replication in genetically modified cell lines
time frame: 3 years
description: HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
measure: Anti-viral responses in primary keratinocytes
time frame: 3 years
description: Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])
measure: Anti-viral responses in fibroblasts
time frame: 3 years
description: Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])
measure: Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)
time frame: 3 years
description: Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).
measure: Anti-viral responses in genetically modified cell lines
time frame: 3 years
description: Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).
measure: Immune responses in primary keratinocytes
time frame: 3 years
description: Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).
measure: Immune responses in fibroblasts
time frame: 3 years
description: Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).
measure: Immune responses in Plasmacytoid Dendritic Cells (pDCs)
time frame: 3 years
description: Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs]).
measure: Immune responses in genetically modified cell lines
time frame: 3 years
description: Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons [IFNs], tumor necrosis factor alpha [TNFalpha], LL-37, human beta-defensins [HBDs])
measure: Differentiation markers in primary keratinocytes
time frame: 3 years
description: Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
measure: Differentiation markers in genetically modified keratinocyte cell lines
time frame: 3 years
description: Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
measure: Expression of reporter gene constructs testing non-coding variants
time frame: 3 years
measure: Exploratory: Viral carriage
time frame: 3 years
description: Viral carriage will be assessed by presence of viral sequencing reads.
measure: Exploratory: Protein expression of epidermal differentiation complex
time frame: 3 years
description: Protein expression of epidermal differentiation complex will be measured by Mass Spectroscopy of skin tape strips.
measure: Exploratory: Protein expression of inflammatory genes
time frame: 3 years
description: Protein expression of inflammatory genes will be measured by Mass Spectroscopy of skin tape strips.
measure: Exploratory: Lipid profiles
time frame: 3 years
description: Lipid profiles will be measured by mass spectroscopy of skin tape strips.
measure: Exploratory: Whole-genome DNA methylation profiles from epidermis
time frame: 3 years
measure: Exploratory: Whole-genome DNA methylation profiles from dermis
time frame: 3 Years
arm group label: Discovery Cohort
description: A minimum of 50 recurrent Atopic Dermatitis with a history of Eczema Herpeticum(ADEH+), 500 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-), and 237 Non-Atopic (NA) European American participants from the Atopic Dermatitis Research Network (ADRN) DNA Repository.
The study will learn from this cohort:
All Single Nucleotide Variants (SNVs) in ADEH+
ADEH+ specific deleterious SNVs
The study will determine the function of:
4. ADEH+ risk variants
arm group label: Independent populations of participants
description: Two independent populations of participants:
Children, aged 3-17 years and
Adults 18-64 years of age.
A minimum of 12 recurrent Atopic Dermatitis with a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, 12 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-) and 12 Non-Atopic (NA) participants will be enrolled in each of the two populations.
Blood and Skin Tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 3 Years
maximum age: 64 Years
healthy volunteers: No
last name: Donald Leung, M.D., Ph.D.
role: Study Chair
affiliation: National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
facility: 
country: United States
url: https://clinicaltrials.gov/ct2/show/NCT01494142
description: ClinicalTrials.gov Record for Atopic Dermatitis Research Network Registry
url: https://www.niaid.nih.gov/
description: National Institute of Allergy and Infectious Diseases (NIAID) website
url: https://www.niaid.nih.gov/research/atopic-dermatitis-research-network
description: Atopic Dermatitis Research Network (ADRN) information
responsible party type: Sponsor
mesh term: Kaposi Varicelliform Eruption
mesh term: Eczema