Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Immune Response to Yellow Fever Vaccination in Adults With Atopic Dermatitis

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.
 
ClinicalTrials.gov Identifier: NCT00723489
Recruitment Status : Completed
First Posted : July 28, 2008
Results First Posted : September 30, 2013
Last Update Posted : January 13, 2014
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The main objective of the Atopic Dermatitis and Vaccinia Immunization Network (ADVN) is to reduce the risk of the fatal reaction, eczema vaccinatum (EV), to the smallpox vaccination in those with atopic dermatitis (AD). Since vaccination with live vaccinia virus (VV) in individuals with AD increases the risk of EV, a yellow fever vaccine was chosen. The purpose of this study is to determine the immune response to a yellow fever vaccine in adults with AD.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Biological: Live Yellow Fever Vaccine (YFV-17D) Drug: YFV-17D Placebo Phase 1 Phase 2

Detailed Description:

AD is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. The purpose of this study is to understand the immune response to a yellow fever vaccine in adults with AD. This study will provide substantial information about normal and defective cutaneous immunity in participants with AD in response to a live virus vaccine, which is critical for understanding the EV reaction.

An individual's participation in the study will last up to 13 weeks. Participants will be randomized into one of two arms. The first experimental arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D by subcutaneous administration in the right deltoid and receive one dose of YFV-17D placebo by transcutaneous administration in the left deltoid. The second arm will consist of 20 adults with AD and 20 healthy adults. They will receive one dose of YFV-17D placebo by subcutaneous administration in the right deltoid and receive one dose of YFV-17D vaccine transcutaneously in the left deltoid.

This study will consist of 6 follow-up visits over a 35 day period after study entry.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Study of the Systemic and Cutaneous Immune Responses to Yellow Fever Vaccination in Atopic Dermatitis Subjects
Study Start Date : August 2008
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema Fever Vaccines

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: YFV-17D (Right Deltoid)
Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccine administration. In this arm, participants will receive a standard vaccine dose (5.5x10^4 Plaque Forming Units) of YFV-17D administered subcutaneously in the right deltoid and placebo vaccination transcutaneously (then covered with a semi-occlusive dressing) in the left deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administer assigned treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial.
 Biological: Live Yellow Fever Vaccine (YFV-17D)
Drug: YFV-17D Placebo
Experimental: YFV-17D (Left Deltoid)
Participants will be randomized within each atopic dermatitis (AD) severity subgroup or as non-atopic controls to either subcutaneous (SC) or transcutaneous (TC) vaccination. In this arm, participants will receive YFV-17D vaccination (1x10^3 Plaque Forming Units) by transcutaneous administration (then covered with a semi-occlusive dressing to optimize YFV-17D absorption) in the left deltoid and placebo by subcutaneous administration in the right deltoid. The site pharmacist will maintain the blind and an unblinded (i.e., masked) site coordinator will administered treatment: investigators, participants and assessors remain blinded to treatment assignments throughout the duration of the trial.
 Biological: Live Yellow Fever Vaccine (YFV-17D)
Drug: YFV-17D Placebo


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D TC- (AD) Participants Compared to YFV-17D TC- (Non-AD) Participants [ Time Frame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) ]
    Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.

  2. Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralization Index (LNI): YFV-17D SC - (AD) Participants Compared to YFV-17D SC- (Non-AD) Participants [ Time Frame: 30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization) ]
    Log10 Neutralization Index (LNI) is the Log10 difference in virus titer (measurement of amount of virus) between pre-vaccination and post-vaccination. An LNI greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.

  3. Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D TC - (AD) Participants Compared to YFV-17D TC - (Non - AD) Participants [ Time Frame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) ]
    Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus.

  4. Comparison of Anti-YF Antibody Levels by Measurement of Log10 Neutralizing Titer 50 (NT50): YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants [ Time Frame: 30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization) ]
    Neutralization titer (NT50) is the dilution of serum (antibody) that results in a 50% reduction in the amount of virus. A higher NT50 number reflects the presence of more protective antibody levels against the Yellow Fever virus. Some studies have used an NT50 titer of 1:10 or 1:20 as the minimum level to suggest that a person has active immunity against the Yellow Fever virus.


Secondary Outcome Measures :
  1. Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants [ Time Frame: Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35) ]
    Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.

  2. Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants [ Time Frame: Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35) ]
    Seroconversion is defined as a Log10 Neutralization Index (LNI) of 0.7 or higher. A value greater than or equal to 0.7 suggests that a person has active immunity against Yellow Fever virus.

  3. Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD4 Positive T-cells, YFV-17D SC - (AD) Compared to YFV-17D SC - (Non- AD) Participants [ Time Frame: Day 30 (Day 28-35) ]
    Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD4 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T-cells on Day 30 (acceptable blood draw window: Day 28 - 35).

  4. Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive , CD4 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants [ Time Frame: Day 30 (Day 28-35) ]
    Comparison by designated reporting groups: the Log10 transformed count of CD4 Positive T-cells that express IFN-gamma and TNF-alpha in every 10^6 CD4 Positive T- Cells (Day 30). A higher count reflects a better immune response to Yellow Fever virus.

  5. Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D SC -(AD) Compared to YFV-17D SC - (Non-AD) Participants [ Time Frame: Day 30 (Day 28-35) ]
    Comparison by designated reporting groups: the Log10 transformed lymphocyte count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells.

  6. Comparison in Log10 Transformed Lymphocyte Count on Day 30 Post YF Immunization: IFN-gamma Positive, Tumor Necrosis Factor- Alpha (TNF Alpha) Positive, CD8 Positive T-cells, YFV-17D TC - (AD) Compared to YFV-17D TC - (Non-AD) Participants [ Time Frame: Day 30 (Day 28-35) ]
    Comparison by designated reporting groups: the Log10 transformed count of CD8 Positive T-cells expressing IFN-gamma and TNF-alpha in every 10^6 CD8 Positive T-cells.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   27 Years to 43 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Diagnosis of Atopic Dermatitis or Non-atopic control
  • Born and currently residing in the United States
  • Weight of at least 110 lbs at the Screening Visit
  • Not previously vaccinated for YFV, tick-borne encephalitis (TBEV), Japanese encephalitis virus (JEV), or dengue fever
  • Agree to use adequate contraception 30 days prior to and until their participation in the study is completed. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • AD subjects with exfoliative erythroderma or lacking a minimum 10 cm diameter area of normal appearing skin on the deltoid or thigh vaccination sites
  • Have a body mass index (BMI) of 30 or greater at the Screening Visit
  • Known history of infection with YFV, dengue fever, TBEV, JEV, or West Nile Virus (WNV)
  • A family history of severe reactions to the yellow fever vaccine
  • Traveled to Africa or South America (including participants who plan to travel to these areas prior to completion of the study)
  • History of egg allergy or have a positive egg allergy skin prick test that is administered at the Screening visit
  • History of acute hypersensitivity reaction to any components of the yellow fever vaccine (including gelatin)
  • Have latex allergy
  • Have lidocaine allergy
  • Are allergic or hypersensitive to TegadermTM
  • Received systemic immunosuppressants within 30 days prior to receiving the vaccination
  • Received systemic corticosteroids, anti inflammatory biologics (e.g., alefacept, etanercept, etc.), or calcineurin inhibitors within 30 days prior to receiving the vaccination
  • Received systemic antibiotics or antivirals within 7 days of receiving the vaccination
  • Received greater than 440 mcg of inhaled steroids per day within 6 months prior to receiving the vaccination
  • Received Xolair (Omalizumab) within 1 year prior to receiving the vaccination
  • Received immunotherapy within 30 days prior to receiving the vaccination
  • Received any vaccine within 30 days prior to randomization or expected receipt 30 days after randomization
  • Received topical antibiotics, antivirals, immune enhancers (e.g., imiquimod), or calcineurin inhibitors within 7 days prior to receiving the vaccination
  • Received topical corticosteroids within 7 days prior to receiving the vaccination
  • Received phototherapy (e.g., ultraviolet light B [UVB], psoralen plus ultraviolet light A [PUVA]) within 30 days prior to receiving the vaccination
  • Acute febrile illness or active fungal, bacterial, or viral infections (subjects may be reconsidered for enrollment once the condition has resolved)
  • Skin disease other than AD that might compromise the stratum corneum barrier (e.g., clinically evident ichthyosis, bullous disease, psoriasis)
  • Current or past history of malignancy or of autoimmune or immunodeficiency diseases. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding
  • Have an anti-nuclear antibody (ANA) titer that is equal to or greater than 1/160 at the Screening Visit
  • Have a serum immunoglobulin (Ig)G, IgM, IgA, C3, or C4 level below the normal range at the Screening Visit
  • Have a manual lymphocyte count that is less than 1000 lymphocytes per microliter
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT00723489


Locations
Layout table for location information
United States, California
University of California, San Diego
San Diego, California, United States, 92037
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Layout table for investigator information
Study Chair: Jon Hanifin, M.D. Oregon Health and Science University
Principal Investigator: Mark Slifka, Ph.D. Oregon Health and Science University
Principal Investigator: Eric Simpson, M.D. Oregon Health and Science University
Principal Investigator: Henry Milgrom, M.D. National Jewish Health
Principal Investigator: Richard Gallo, M.D., Ph.D. University of California, San Diego
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00723489    
Other Study ID Numbers: DAIT ADVN YF08
HHSN266200400029C
First Posted: July 28, 2008    Key Record Dates
Results First Posted: September 30, 2013
Last Update Posted: January 13, 2014
Last Verified: December 2013
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Yellow Fever Vaccine
Scarification Method
Atopic Dermatitis
IgG antibodies
Additional relevant MeSH terms:
Layout table for MeSH terms
Yellow Fever
Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
 Immune System Diseases
Arbovirus Infections
Vector Borne Diseases
Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral