Eczema HerpeticumNCT03038932

Etiology of Eczema Herpeticum (EH)

An observational study of Eczema Herpeticum, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 64 years
Conditions the study is for: Eczema Herpeticum
How many people: 69 participants
Where: 1 siteUnited States
Study dates: 22 Feb 2017to 24 Nov 2020
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 64 years
All sexes
No healthy volunteers
Child, Adult

Study population: 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 protocol will also enroll two independent populations of participants 1) children, 3-17 years of age and 2) adults 18-64 years of age. A minimum of 12 recurrent ADEH+ with ≥3 EH episodes, 12 ADEH- and 12 NA participants will be enrolled in each of the two populations.

Who may be able to join

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.

Who cannot join

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);

Show all 10Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Denver, Colorado, 80206

Other trials in United States

About this study

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

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.

Read the detailed 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.

Conditions: Eczema Herpeticum
Keywords: whole genome sequencing (WGS)
Medical subject headings: Kaposi Varicelliform Eruption

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03038932
Study group	Role	What they receive
Discovery Cohort		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: 1. All Single Nucleotide Variants (SNVs) in ADEH+ 2. ADEH+ specific deleterious SNVs The study will determine the function of: 4. ADEH+ risk variants
Independent populations of participants		Two independent populations of participants: 1. Children, aged 3-17 years and 2. 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 3 years
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.
Measured: 3 years

Secondary outcomes (27)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Feb 201724 Nov 2020

First posted1 Feb 2017 (estimated)
Study start22 Feb 2017
Primary completion24 Nov 2020
Study completion24 Nov 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Eczema HerpeticumStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Prospective
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03038932
Sponsor's protocol ID: DAIT ADRN-06
Status last verified: Jan 2021
First submitted: 25 Jan 2017
Last updated: 14 Jan 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Integrated Extreme Trait Analysis to Understand the Etiology of Eczema Herpeticum (ADRN-06)
ClinicalTrials.gov ID: NCT03038932
Acronym / sponsor ID: DAIT ADRN-06
Conditions: Eczema Herpeticum
Keywords: whole genome sequencing (WGS)
Study type: Observational
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: Atopic Dermatitis Research Network, Rho Federal Systems Division, Inc.
Study start: 22 Feb 2017 (actual)
Primary completion: 24 Nov 2020 (actual)
Study completion: 24 Nov 2020 (actual)
First posted: 1 Feb 2017 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Observational model: Case-control
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Discovery Cohort	–	–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: 1. All Single Nucleotide Variants (SNVs) in ADEH+ 2. ADEH+ specific deleterious SNVs The study will determine the function of: 4. ADEH+ risk variants
Independent populations of participants	–	–Two independent populations of participants: 1. Children, aged 3-17 years and 2. 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.

Who may qualify

Ages: 3 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult
Study population: 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 protocol will also enroll two independent populations of participants 1) children, 3-17 years of age and 2) adults 18-64 years of age. A minimum of 12 recurrent ADEH+ with ≥3 EH episodes, 12 ADEH- and 12 NA participants will be enrolled in each of the two populations.

Key inclusion criteria (8 listed)

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

Key exclusion criteria (10 listed)

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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

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.

27 secondary outcomes

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
Herpes Simplex Virus (HSV) replication in fibroblasts
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in genetically modified cell lines
Time frame: 3 years
Anti-viral responses in primary keratinocytes
Time frame: 3 years
Anti-viral responses in fibroblasts
Time frame: 3 years
Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)
Time frame: 3 years
Anti-viral responses in genetically modified cell lines
Time frame: 3 years
Immune responses in primary keratinocytes
Time frame: 3 years
Immune responses in fibroblasts
Time frame: 3 years
Immune responses in Plasmacytoid Dendritic Cells (pDCs)
Time frame: 3 years
Immune responses in genetically modified cell lines
Time frame: 3 years
Differentiation markers in primary keratinocytes
Time frame: 3 years
Differentiation markers in genetically modified keratinocyte cell lines
Time frame: 3 years
Expression of reporter gene constructs testing non-coding variants
Time frame: 3 years
Exploratory: Viral carriage
Time frame: 3 years
Exploratory: Protein expression of epidermal differentiation complex
Time frame: 3 years
Exploratory: Protein expression of inflammatory genes
Time frame: 3 years
Exploratory: Lipid profiles
Time frame: 3 years
Exploratory: Whole-genome DNA methylation profiles from epidermis
Time frame: 3 years
Exploratory: Whole-genome DNA methylation profiles from dermis
Time frame: 3 Years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
ClinicalTrials.gov Record for Atopic Dermatitis Research Network RegistryLink provided by the sponsor.
National Institute of Allergy and Infectious Diseases (NIAID) websiteLink provided by the sponsor.
Atopic Dermatitis Research Network (ADRN) informationLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Donald Leung, M.D., Ph.D. study chair

National Jewish Health: Division of Pediatric Allergy and Clinical Immunology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Eczema Herpeticum, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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 (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03038932.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2021.