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Interferon Responses in Eczema Herpeticum (ADRN-01)

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ClinicalTrials.gov Identifier: NCT01429311
Recruitment Status : Completed
First Posted : September 7, 2011
Last Update Posted : April 28, 2017
Sponsor:
Collaborator:
Atopic Dermatitis Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

July 19, 2011
September 7, 2011
April 28, 2017
April 2011
January 2016   (Final data collection date for primary outcome measure)
Expression of IFNγ and Interleukin-12 (IL-12), in response to stimulation with Herpes Simplex Virus 1 (HSV-1), Vaccinia Virus (VV), and Pattern Recognition Receptors (PRR) agonists [ Time Frame: Day 1 ]
Protein and messenger ribonucleic acid (mRNA) levels of IFNγ, and the IFN-γ promoting cytokine, IL-12, produced by Cluster of Differentiation 14 (CD14+) monocytes in response to stimulation with HSV-1, VV, and various PRR agonists
Expression of IFN and IL-12, in response to stimulation with HSV-1, VV, and PRR agonists. [ Time Frame: Day 1 ]
Messenger ribonucleic acid (mRNA) levels of IFN, and the IFN promoting cytokine, IL-12, produced by CD14+ monocytes in response to stimulation with HSV-1, VV, and various PRR agonists.
Complete list of historical versions of study NCT01429311 on ClinicalTrials.gov Archive Site
  • Cell surface expression of Major Histocompatibility complex (MHC) class I and class II and co-stimulatory molecules on CD14+ cells in response to IFNγ and Interferon-alpha (IFNα) stimulation [ Time Frame: Day 1 ]
  • Production of IL-18 and IFNα protein and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists [ Time Frame: Day 1 ]
  • Production of IFNγ protein by Cluster of Differentiation 8 (CD8+) T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFNα [ Time Frame: Day 1 ]
  • Protein expression of IFNγ receptor and IFNα/β receptor on CD14+ cells [ Time Frame: Day 1 ]
  • Immunodominant HSV-1 peptide repertoires [ Time Frame: Day 1 ]
    Analysis of immunodominant HSV-1 peptide repertoires with related Human Leukocyte Antigen (HLA) in ADEH+, ADEH-, and non-atopic participants
  • High-throughput gene expression profiling to analyze ribonucleic acid (RNA) from HSV-1 stimulated and sham stimulated CD14+ monocytes [ Time Frame: Day 1 ]
    Global transcriptional response of CD14+ monocytes to stimulation with HSV-1 as evaluated by GeneChip Profiling
  • Production of protein and RNA of IFN family members and any related pro- or anti-inflammatory cytokines/chemokines in response to stimulation of PBMCs or purified monocytes [ Time Frame: Day 1 ]
    IFN family members include IFNα, Interferon beta (IFNβ), and IFNγ. Related pro- or anti-inflammatory cytokines/chemokines include, but are not limited to IL-29 and IL-10
  • Expression of MHC and co-stimulatory molecules on CD14+ cells in response to stimulation with HSV-1, VV, or PRR agonists [ Time Frame: Day 1 ]
  • Viral titer of VV as determined by plaque assay following incubation of virus with PBMCs [ Time Frame: Day 1 ]
  • Gene expression profiles and gene variant profiles of PBMCs stimulated with HSV-1 as assayed by RNA-seq [ Time Frame: Day 1 ]
  • Cell surface expression of MHC class I/II and co-stimulatory molecules on CD14+ cells in response to IFN-gamma and IFN-alpha. [ Time Frame: Day 1 ]
    Expression of MHC class I/II and co-stimulatory molecules on CD14+ monocytes in response to IFN-gamma and IFN-alpha stimulation.
  • IL-18 and IFN-α by CD14+ cells following stimulation with HSV-1, VV, and PRR agonists. [ Time Frame: Day 1 ]
    Production of IL-18 and IFN-α and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists.
  • IFN-γ production by CD8+ T cells, in response to stimulation with cytokines IL-12, IL-18, and IFN-α. [ Time Frame: Day 1 ]
    Production of IFN-γ by CD8+ T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFN-α.
  • Expression of IFN-γ receptor and IFN- α/β receptor on CD14+ cells. [ Time Frame: Day 1 ]
    Expression of IFN-γ receptor and IFN- α/β receptor on CD14+ cells.
  • Immunodominant HSV-1 peptide repertoires. [ Time Frame: Day 1 ]
    Analysis of immunodominant HSV-1 peptide repertoires with related HLA in ADEH+, ADEH-, and non-atopic participants.
  • High-throughput gene expression profiling to analyze ribonucleic acid (RNA) from HSV-1 stimulated and sham stimulated CD14+ monocytes. [ Time Frame: Day 1 ]
    Global transcriptional response of CD14+ monocytes to stimulation with HSV-1 as evaluated by GeneChip Profiling.
Not Provided
Not Provided
 
Interferon Responses in Eczema Herpeticum
Investigation of Reduced Interferon Responses in Peripheral Blood Mononuclear Cells of Participants With Atopic Dermatitis and a History of Eczema Herpeticum (ADRN-01)
Atopic dermatitis (AD) is a chronic skin disorder characterized by recurrent viral skin infections. A small subset of patients with AD suffer from disseminated viral infections, e.g., eczema herpeticum (ADEH+), after herpes simplex infection (HSV) or eczema vaccinatum (EV) after smallpox vaccination. Interferon gamma (IFNγ) plays a critical role in the innate and acquired immune responses by activating macrophages, enhancing natural killer cell activation, and promoting T cell differentiation, as well as regulating B cell isotype switching to immunoglobulin (Ig) G2a. Recent studies have demonstrated that IFNγ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFNγ induction leads to susceptibility to HSV infection in ADEH+ patients.

The investigators hypothesize that defective IFNγ responses in peripheral blood mononuclear cells (PBMCs) from ADEH+ patients results from aberrant pattern recognition receptors (PRR) signaling in antigen-presenting cells (APCs) resulting in low level production of IL-12, an essential cytokine for IFNγ generation. This study will compare results from 40 ADEH+, 40 ADEH-, and 40 non-atopic participants.

Study procedures will typically be completed in one visit; however, participants may be asked to return for additional unscheduled visit(s) occurring as frequently as every 3 months for the duration of the study to provide an additional blood sample for further characterization of immune mechanisms leading to reduced IFNγ responses in ADEH+.

Observational
Observational Model: Other
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
Blood samples, RNA, serum, protein and cells will be retained.
Non-Probability Sample
40 ADEH+, 40 ADEH-, and 40 non-atopic controls ages 6 to 65 years. Initially, 20 ADEH- and 20 non-atopic control participants will be gender- and age-matched (plus or minus 10 years) to 20 ADEH+ participants. Afterwards, additional participants will be enrolled such that the gender ratio and the age distribution of the ADEH+ participants will be similar to that of the ADEH- and non-atopic control participants
  • Atopic Dermatitis
  • Eczema Herpeticum
  • Herpes Simplex Infections
  • Eczema Vaccinatum
Not Provided
  • ADEH+
    Subjects classified as Atopic Dermatitis (AD) and history of previous Eczema Herpeticum (EH) as defined by the ADRN Standard Diagnostic Criteria
  • ADEH-
    Subjects classified as AD without a history of EH as defined by the ADRN Standard Diagnostic Criteria
  • Non-atopic Controls
    Subjects classified as "Non-Atopic controls" as defined by the ADRN Standard Diagnostic Criteria

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
84
60
January 2016
January 2016   (Final data collection date for primary outcome measure)

Participant Inclusion Criteria:

Participants who meet all of the following criteria are eligible for enrollment:

  • have a history of AD with or without a history of Eczema Herpeticum (EH) as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria OR

    --are non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria

  • are willing to sign the informed consent form or whose parent or legal guardian is willing to sign the informed consent form (age appropriate) prior to initiation of any study procedure
  • are willing to sign the assent form, if age appropriate.

Participant Exclusion Criteria:

Participants who meet any of the following criteria are not eligible for enrollment:

  • have a history of any systemic illness (e.g., immunodeficiency disorders such as human immunodeficiency virus [HIV] or lupus erythematosus) other than the condition being studied
  • have an active systemic malignancy, excluding uncomplicated non-melanoma skin cancer
  • have any skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous disease, psoriasis, cutaneous T cell lymphoma [also called Mycosis Fungoides or Sezary syndrome], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease)
  • have a first degree relative already enrolled in the study
  • are determined not to be eligible in the opinion of the Investigator.

Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed:

  • have active eczema herpeticum at the Enrollment Visit
  • have taken systemic immunosuppressive drugs including cyclosporine or oral steroids within 30 days of the Enrollment Visit
  • have a fever ≥ 38.5 degrees Centigrade (ºC) (101.3 ºF) at the Enrollment Visit.
Sexes Eligible for Study: All
6 Years to 65 Years   (Child, Adult, Older Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01429311
DAIT ADRN-01
NIAID Funding Mechanism ( Other Grant/Funding Number: HHSN272201000020C and HHSN272201000017C )
No
Not Provided
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Atopic Dermatitis Research Network
Principal Investigator: Donald Leung, PhD, M.D National Jewish Health
National Institute of Allergy and Infectious Diseases (NIAID)
April 2017