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Completed

NCT Number: NCT03038932

Etiology of Eczema Herpeticum (EH)

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.

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Key information

Age range

3 year–64 year

Sex eligibility

All sexes

Study type

Observational

Primary location

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

Denver, Colorado, 80206, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must be a participant already enrolled in the ADRN Registry and provided DNA (ClinicalTrials.gov ID: NCT01494142);
  • Participant and/or parent guardian must be able to understand and provide informed consent;
  • A history of Atopic Dermatitis (AD) with a history of eczema herpeticum (ADEH+), as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria, with ≥3 episodes of Eczema Herpeticum (EH)

OR

A history of AD without a history of eczema herpeticum (ADEH-), as diagnosed using the ADRN Standard Diagnostic Criteria, and no immediate family members (mother, father, full siblings, half-siblings, offspring, aunts, uncles, cousins, or grandparents) with a history of EH

OR

Non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria.

  • Anti-Herpes Simplex Virus (HSV)-1 or Anti-HSV-2 Immunoglobulin G (IgG) seropositive.

Exclusion criteria

  • Inability or unwillingness of a participant and/or parent guardian to give written informed consent or comply with study protocol;
  • Pregnant or lactating women;
  • Known or suspected immunosuppression;
  • Severe concomitant illness(es);
  • History of keloid formation (adults only);
  • History of lidocaine or Novocain allergy (adults only);
  • History of serious life-threatening reaction to latex, tape, or adhesives;
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
  • Use of biologics within 5 half-lives (if known) or 16 weeks of the Screening Visit;
  • Use of an investigational drug within 5 half-lives (if known) or 8 weeks of the Screening Visit.

Treatment and study plan

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. Gene expression profiles in the dermis

    Time frame: 3 years

  2. Gene expression profiles in the epidermis

    Time frame: 3 years

  3. Gene expression profiles in in keratinocytes

    Time frame: 3 years

  4. Gene expression profiles in fibroblasts

    Time frame: 3 years

  5. Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)

    Time frame: 3 years

  6. Gene expression profiles in skin tape strip samples

    Time frame: 3 years

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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])

  12. 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])

  13. 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]).

  14. 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]).

  15. 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]).

  16. 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]).

  17. 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]).

  18. 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])

  19. Differentiation markers in primary keratinocytes

    Time frame: 3 years

    Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).

  20. 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)).

  21. Expression of reporter gene constructs testing non-coding variants

    Time frame: 3 years

  22. Exploratory: Viral carriage

    Time frame: 3 years

    Viral carriage will be assessed by presence of viral sequencing reads.

  23. Exploratory: Protein expression of epidermal differentiation complex

    Time frame: 3 years

    Protein expression of epidermal differentiation complex will be measured by Mass Spectroscopy of skin tape strips.

  24. Exploratory: Protein expression of inflammatory genes

    Time frame: 3 years

    Protein expression of inflammatory genes will be measured by Mass Spectroscopy of skin tape strips.

  25. Exploratory: Lipid profiles

    Time frame: 3 years

    Lipid profiles will be measured by mass spectroscopy of skin tape strips.

  26. Exploratory: Whole-genome DNA methylation profiles from epidermis

    Time frame: 3 years

  27. Exploratory: Whole-genome DNA methylation profiles from dermis

    Time frame: 3 Years

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Collaborators

  • Atopic Dermatitis Research Network
  • Rho Federal Systems Division, Inc.

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Feb 1, 2017
Registry last updated
Jan 14, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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