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Interferon Responses in Eczema Herpeticum (ADRN-01)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01429311
First Posted: September 7, 2011
Last Update Posted: April 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Atopic Dermatitis Research Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
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.

Condition
Atopic Dermatitis Eczema Herpeticum Herpes Simplex Infections Eczema Vaccinatum

Study Type: Observational
Study Design: Observational Model: Other
Time Perspective: Prospective
Official Title: Investigation of Reduced Interferon Responses in Peripheral Blood Mononuclear Cells of Participants With Atopic Dermatitis and a History of Eczema Herpeticum (ADRN-01)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA
Blood samples, RNA, serum, protein and cells will be retained.

Enrollment: 84
Study Start Date: April 2011
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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+.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
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
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01429311


Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Atopic Dermatitis Research Network
Investigators
Principal Investigator: Donald Leung, PhD, M.D National Jewish Health
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01429311     History of Changes
Other Study ID Numbers: DAIT ADRN-01
NIAID Funding Mechanism ( Other Grant/Funding Number: HHSN272201000020C and HHSN272201000017C )
First Submitted: July 19, 2011
First Posted: September 7, 2011
Last Update Posted: April 28, 2017
Last Verified: April 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Atopic Dermatitis
Eczema herpeticum
Interferon gamma
IFNγ

Additional relevant MeSH terms:
Eczema
Dermatitis
Dermatitis, Atopic
Herpes Simplex
Kaposi Varicelliform Eruption
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Interferons
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents