Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00407069
First received: November 30, 2006
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. Recent studies have demonstrated that the skin of people with AD my have decreased antimicrobial peptide (AMP) expression. The purpose of this study is to compare smallpox virus replication and the number of AMPs and other antiviral molecules in people with AD, as compared to those seen in people with psoriasis or asthma, or healthy individuals.


Condition
Atopic Dermatitis

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Role of Antimicrobial Peptides in Host Defense Against Vaccinia Virus (ADVN AMP01)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Expression of vaccinia virus mRNA in non-lesional skin following inoculation with untreated vaccinia virus will be evaluated using real-time RT-PCR (Reverse transcription polymerase chain reaction). [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Expression of cytokines, AMPs, other antiviral molecules, or epidermal differentiation proteins in non-lesional skin prior to and after inoculation with vaccinia virus will be evaluated using real-time RT-PCR. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Keratinocytes will be stimulated with vaccinia virus in the presence and absence of Th1 or Th2 cytokines. Non-lesional AD skin will be stimulated with vaccinia virus in the presence of antibodies that neutralize Th2 cytokines. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Vaccinia virus replication will be evaluated using a standard viral plaque assay in BS-C-1 cells and by analyzing vaccinia virus mRNA expression using real-time RT-PCR in keratinocytes and BS-C-1 cells. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Expression of over 20,000 genes will be evaluated by GeneChip microarrays in non-lesional skin, and PBMCs stimulated with vaccinia virus. Real-time RT-PCR of skin and PBMC will be used to confirm gene alterations found in GeneChip microarrays. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Ability of structural analogues of CSAs (Cyclosporine) to kill purified vaccinia virus as well as keratinocytes infected with vaccinia virus in vitro. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood and skin samples will be retained


Enrollment: 286
Study Start Date: June 2005
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
Active Atopic Dermatitis (AD)
Pediatric and adult subjects who fulfill the criteria for AD, a chronic inflammatory skin disease.
Inactive Atopic Dermatitis (AD)
Adult subjects with a prior history of active AD that has been quiescent for at least 1 year.
Psoriatics
Adult subjects who fulfill the criteria for plaque psoriasis, a chronic inflammatory skin disease.
Asthmatics (without a history of AD)
Adult subjects who fulfill the criteria for asthma (reactive airway disease) and have a negative history of skin disease.
Eczema Herpeticum (EH
Pediatric and adult AD subjects with a history of EH.
Healthy Volunteers
Healthy individuals with no history of skin or respiratory disease.

Detailed Description:

AD is a chronic inflammatory skin disease characterized by frequent viral skin infections. Recent studies have found that components in the skin of people with AD may block AMP expression. AMPs are responsible for preventing infection from viruses. The purpose of this study is to examine smallpox virus replication and AMP expression in the skin of patients with AD as well as identify other antiviral molecules involved in immune response. These findings will be compared with those of people with psoriasis or asthma, or healthy individuals. This study will consist of one study visit at which skin and blood samples will be taken.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

People of good general health

Criteria

Inclusion Criteria for Participants With AD:

  • 2 years of age or older
  • History of active or inactive AD OR eczema herpeticum, as defined by the ADVN standardized diagnostic criteria
  • Parent or guardian willing to provide informed consent, if applicable
  • Male or female of any race and ethnicity

Inclusion Criteria for Participants With Asthma or Psoriasis, and for non-atopic controls:

  • 18 years or older
  • History of psoriasis OR history of asthma not requiring systemic medications
  • Parent or guardian willing to provide informed consent, if applicable
  • Male or female of any race and ethnicity

Exclusion Criteria:

  • Oral corticosteroids or any systemic immunosuppressive or immunomodulatory medication within 28 days prior to study entry
  • Immunotherapy within 3 months prior to study entry
  • History of bleeding disorder
  • Aspirin, oral antihistamines, oral antibiotics, oral cyclosporine, or topical medications within 7 days of screening visit including, but not restricted to, Protopic, Elidel, topical corticosteroids, and topical antibiotics
  • Anxiolytic agents and antidepressants within 2 days of screening visit
  • Diabetic requiring medication
  • Autoimmune or immunodeficiency
  • Active fungal, bacterial, or viral infections within 7 days prior to study entry
  • Active systemic cancer. Participants with uncomplicated nonmelanoma skin cancer are not excluded.
  • Theophylline or leukotriene antagonists within 24 hours of screening visit
  • Received any vaccination within 30 days prior to study entry
  • Known lidocaine allergy
  • Previously vaccinated for smallpox
  • Pregnant or breastfeeding
  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: NCT00407069

Locations
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80207
Sponsors and Collaborators
Investigators
Principal Investigator: Donald Leung MD, PhD National Jewish Health
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00407069     History of Changes
Other Study ID Numbers: DAIT ADVN AMP 01
Study First Received: November 30, 2006
Last Updated: April 1, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Dermatitis
Dermatitis, Atopic
Vaccinia
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014