Etiology of Eczema Herpeticum (EH)

Eczema Herpeticum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03038932
• Other study ID #: DAIT ADRN-06
• Status: Completed
• Start date: February 22, 2017
• Est. completion date: November 24, 2020

Study information

• Verified date: January 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: November 24, 2020
• Est. primary completion date: November 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 64 Years

Eligibility

Inclusion Criteria:

1. Must be a participant already enrolled in the ADRN Registry and provided DNA (ClinicalTrials.gov ID: NCT01494142);

2. Participant and/or parent guardian must be able to understand and provide informed consent;

3. 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.

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

Exclusion Criteria:

1. Inability or unwillingness of a participant and/or parent guardian to give written informed consent or comply with study protocol;

2. Pregnant or lactating women;

3. Known or suspected immunosuppression;

4. Severe concomitant illness(es);

5. History of keloid formation (adults only);

6. History of lidocaine or Novocain allergy (adults only);

7. History of serious life-threatening reaction to latex, tape, or adhesives;

8. 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.

9. Use of biologics within 5 half-lives (if known) or 16 weeks of the Screening Visit;

10. Use of an investigational drug within 5 half-lives (if known) or 8 weeks of the Screening Visit.

Related Conditions & MeSH terms

• Eczema
• Eczema Herpeticum

Locations

Country	Name	City	State
United States	National Jewish Health: Division of Pediatric Allergy and Clinical Immunology	Denver	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Atopic Dermatitis Research Network, Rho Federal Systems Division, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	3 years
Primary	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	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.	3 years
Secondary	Gene expression profiles in the dermis		3 years
Secondary	Gene expression profiles in the epidermis		3 years
Secondary	Gene expression profiles in in keratinocytes		3 years
Secondary	Gene expression profiles in fibroblasts		3 years
Secondary	Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)		3 years
Secondary	Gene expression profiles in skin tape strip samples		3 years
Secondary	Herpes Simplex Virus (HSV) replication in primary keratinocytes	HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.	3 years
Secondary	Herpes Simplex Virus (HSV) replication in fibroblasts	HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.	3 years
Secondary	Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)	HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.	3 years
Secondary	Herpes Simplex Virus (HSV) replication in genetically modified cell lines	HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.	3 years
Secondary	Anti-viral responses in primary keratinocytes	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])	3 years
Secondary	Anti-viral responses in fibroblasts	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])	3 years
Secondary	Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)	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]).	3 years
Secondary	Anti-viral responses in genetically modified cell lines	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]).	3 years
Secondary	Immune responses in primary keratinocytes	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]).	3 years
Secondary	Immune responses in fibroblasts	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]).	3 years
Secondary	Immune responses in Plasmacytoid Dendritic Cells (pDCs)	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]).	3 years
Secondary	Immune responses in genetically modified cell lines	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])	3 years
Secondary	Differentiation markers in primary keratinocytes	Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).	3 years
Secondary	Differentiation markers in genetically modified keratinocyte cell lines	Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).	3 years
Secondary	Expression of reporter gene constructs testing non-coding variants		3 years
Secondary	Exploratory: Viral carriage	Viral carriage will be assessed by presence of viral sequencing reads.	3 years
Secondary	Exploratory: Protein expression of epidermal differentiation complex	Protein expression of epidermal differentiation complex will be measured by Mass Spectroscopy of skin tape strips.	3 years
Secondary	Exploratory: Protein expression of inflammatory genes	Protein expression of inflammatory genes will be measured by Mass Spectroscopy of skin tape strips.	3 years
Secondary	Exploratory: Lipid profiles	Lipid profiles will be measured by mass spectroscopy of skin tape strips.	3 years
Secondary	Exploratory: Whole-genome DNA methylation profiles from epidermis		3 years
Secondary	Exploratory: Whole-genome DNA methylation profiles from dermis		3 Years

External Links

•   Atopic Dermatitis Research Network (ADRN) information
•   ClinicalTrials.gov Record for Atopic Dermatitis Research Network Registry
•   National Institute of Allergy and Infectious Diseases (NIAID) website