Integrated Extreme Trait Analysis to Understand the Etiology of Eczema Herpeticum (ADRN-06)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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
- •Non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria.
- •Anti-Herpes Simplex Virus (HSV)-1 or Anti-HSV-2 Immunoglobulin G (IgG) seropositive.
排除标准
- •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.
结局指标
主要结局
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
时间窗: 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.
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
时间窗: 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.
次要结局
- Gene expression profiles in the dermis(3 years)
- Gene expression profiles in the epidermis(3 years)
- Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)(3 years)
- Herpes Simplex Virus (HSV) replication in genetically modified cell lines(3 years)
- Herpes Simplex Virus (HSV) replication in primary keratinocytes(3 years)
- Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)(3 years)
- Exploratory: Viral carriage(3 years)
- Exploratory: Protein expression of epidermal differentiation complex(3 years)
- Exploratory: Protein expression of inflammatory genes(3 years)
- Gene expression profiles in skin tape strip samples(3 years)
- Herpes Simplex Virus (HSV) replication in fibroblasts(3 years)
- Immune responses in fibroblasts(3 years)
- Immune responses in Plasmacytoid Dendritic Cells (pDCs)(3 years)
- Exploratory: Whole-genome DNA methylation profiles from epidermis(3 years)
- Gene expression profiles in in keratinocytes(3 years)
- Gene expression profiles in fibroblasts(3 years)
- Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)(3 years)
- Anti-viral responses in primary keratinocytes(3 years)
- Differentiation markers in genetically modified keratinocyte cell lines(3 years)
- Expression of reporter gene constructs testing non-coding variants(3 years)
- Anti-viral responses in fibroblasts(3 years)
- Immune responses in primary keratinocytes(3 years)
- Immune responses in genetically modified cell lines(3 years)
- Differentiation markers in primary keratinocytes(3 years)
- Exploratory: Whole-genome DNA methylation profiles from dermis(3 Years)
- Anti-viral responses in genetically modified cell lines(3 years)
- Exploratory: Lipid profiles(3 years)