Clinical Trial: Etiology of Eczema Herpeticum (EH)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Integrated Extreme Trait Analysis to Understand the Etiology of Eczema Herpeticum (ADRN-06)

Brief Summary:

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.

Detailed Summary:

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.

Current Primary Outcome:

• 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 ]
  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.
• 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 ]
  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.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Gene expression profiles in the dermis [ Time Frame: 3 years ]
• Gene expression profiles in the epidermis [ Time Frame: 3 years ]
• Gene expression profiles in in keratinocytes [ Time Frame: 3 years ]
• Gene expression profiles in fibroblasts [ Time Frame: 3 years ]
• Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs) [ Time Frame: 3 years ]
• Gene expression profiles in skin tape strip samples [ Time Frame: 3 years ]
• Herpes Simplex Virus (HSV) replication in primary keratinocytes [ Time Frame: 3 years ]
  HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
• Herpes Simplex Virus (HSV) replication in fibroblasts [ Time Frame: 3 years ]
  HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
• Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs) [ Time Frame: 3 years ]
  HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
• Herpes Simplex Virus (HSV) replication in genetically modified cell lines [ Time Frame: 3 years ]
  HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
• Anti-viral responses in primary keratinocytes [ Time Frame: 3 years ]
  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])
• Anti-viral responses in fibroblasts [ Time Frame: 3 years ]
  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])
• Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs) [ Time Frame: 3 years ]
  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]).
• Anti-viral responses in genetically modified cell lines [ Time Frame: 3 years ]
  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]).
• Immune responses in primary keratinocytes [ Time Frame: 3 years ]
  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]).
• Immune responses in fibroblasts [ Time Frame: 3 years ]
  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]).
• Immune responses in Plasmacytoid Dendritic Cells (pDCs) [ Time Frame: 3 years ]
  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]).
• Immune responses in genetically modified cell lines [ Time Frame: 3 years ]
  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])
• Differentiation markers in primary keratinocytes [ Time Frame: 3 years ]
  Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
• Differentiation markers in genetically modified keratinocyte cell lines [ Time Frame: 3 years ]
  Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
• Expression of reporter gene constructs testing non-coding variants [ Time Frame: 3 years ]
• Exploratory: Viral carriage [ Time Frame: 3 years ]
  Viral carriage will be assessed by presence of viral sequencing reads.
• Exploratory: Protein expression of epidermal differentiation complex [ Ti
  
  

  Original Secondary Outcome: Same as current
  
  Information By: National Institute of Allergy and Infectious Diseases (NIAID)
  

  Dates:
  Date Received: January 25, 2017
  Date Started: February 22, 2017
  Date Completion: November 2020
  Last Updated: March 2, 2017
  Last Verified: March 2017