Interferon Responses in Eczema Herpeticum (ADEH) (IFN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01429311
First received: July 19, 2011
Last updated: April 14, 2014
Last verified: April 2014
  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 (IFN)-γ 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 IFN-γ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFN-γ 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: 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 Interferon (IFN) and Interleukin (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 ] [ Designated as safety issue: No ]
    Protein and messenger ribonucleic acid (mRNA) levels of Gamma Interferon (IFN-γ), and the IFN-γ promoting cytokine, IL-12, produced by 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/II and co-stimulatory molecules on CD14+ cells in response to IFN-γ and IFN-α stimulation. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Production of IL-18 and IFN-α protein and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Production of IFN-γ protein by CD8+ T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFN-α. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Protein expression of IFN-γ receptor and IFN- α/β receptor on CD14+ cells. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Immunodominant HSV-1 peptide repertoires. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    IFN family members include IFN-α, IFNβ, and IFN-γ. 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 ] [ Designated as safety issue: No ]
  • Viral titer of VV as determined by plaque assay following incubation of virus with PBMCs. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Gene expression profiles and gene variant profiles of PBMCs stimulated with HSV-1 as assayed by RNA-seq. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood samples, RNA, serum, protein and cells will be retained.


Estimated Enrollment: 120
Study Start Date: April 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
40 ADEH+
Participants with AD and history of previous EH
40 ADEH-
Participants with AD without a history of EH
40 Non-atopic controls

Detailed Description:

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 (IFN)-γ 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 IFN-γ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFN-γ induction leads to susceptibility to HSV infection in ADEH+ patients.

We hypothesize that defective IFN-γ responses in 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 IFN-γ generation. We 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)occuring as frequently as every 3 month for the duration of the study provide an additional blood sample for further characterization of immune mechanisms leading to reduced IFN-γ responses in ADEH+.

  Eligibility

Ages Eligible for Study:   6 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

40 ADEH+, 40 ADEH-, and 40 non-atopic controls 6 to 65 years of age. Initially, 20 ADEH- and 20 non-atopic control participants will be gender- and age-matched (± 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. Participants may be reassessed if not initially eligible.

  1. Who 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 who are non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria.
  2. Who 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.
  3. Who 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.

  1. Who 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.
  2. Who have an active systemic malignancy, excluding uncomplicated non-melanoma skin cancer.
  3. Who 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).
  4. Who have a first degree relative already enrolled in the study.
  5. Who 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.

  1. Who have active eczema herpeticum at the Enrollment Visit.
  2. Who have taken systemic immunosuppressive drugs including cyclosporine or oral steroids within 30 days of the Enrollment Visit.
  3. Who have a fever ≥ 38.5 ºC (101.3 ºF) at the Enrollment Visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01429311

Locations
United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Judy Lairsmith    303-270-2413    lairsmithj@NJHealth.org   
Contact: Gayle Spears, NP    (303) 398-1852    spearsg@njhealth.org   
Sponsors and Collaborators
Investigators
Principal Investigator: Donald Leung, PhD, M.D National Jewish Health
  More Information

Additional Information:
No publications provided

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
Study First Received: July 19, 2011
Last Updated: April 14, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Atopic Dermatitis, Eczema herpecticum, Interferon

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

ClinicalTrials.gov processed this record on September 16, 2014