NCT00723489

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2008

Typical duration for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 25, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

July 28, 2008

Completed
4 days until next milestone

Study Start

First participant enrolled

August 1, 2008

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2011

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

September 30, 2013

Completed
Last Updated

January 13, 2014

Status Verified

December 1, 2013

Enrollment Period

2.7 years

First QC Date

July 25, 2008

Results QC Date

July 16, 2013

Last Update Submit

December 11, 2013

Conditions

Atopic Dermatitis

Keywords

Yellow Fever VaccineScarification MethodAtopic DermatitisIgG antibodies

Outcome Measures

Primary Outcomes (4)

  • 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

    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.

    30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

  • 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

    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.

    30 days after YF immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after Yellow Fever immunization)

  • 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

    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.

    30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

  • 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

    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.

    30 days after Yellow Fever (YF) immunization (Acceptable Blood Draw Range: Day 28 - Day 35 after YF immunization)

Secondary Outcomes (6)

  • Comparison of Count of Seroconverters: YFV-17D TC- (AD) Participants Compared to YFV-17D TC - (Non-AD) Participants

    Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)

  • Comparison of Count of Seroconverters: YFV-17D SC - (AD) Participants Compared to YFV-17D SC - (Non-AD) Participants

    Day 0 to Day 30 (Acceptable Post-Vaccination Blood Draw Range: Day 28 - Day 35)

  • 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

    Day 30 (Day 28-35)

  • 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

    Day 30 (Day 28-35)

  • 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

    Day 30 (Day 28-35)

  • +1 more secondary outcomes

Study Arms (2)

YFV-17D (Right Deltoid)

EXPERIMENTAL

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

YFV-17D (Left Deltoid)

EXPERIMENTAL

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

Interventions

Live Yellow Fever Vaccine (YFV-17D)BIOLOGICAL
YFV-17D (Left Deltoid)YFV-17D (Right Deltoid)
YFV-17D PlaceboDRUG
YFV-17D (Left Deltoid)YFV-17D (Right Deltoid)

Eligibility Criteria

Age27 Years - 43 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of California, San Diego

San Diego, California, 92037, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

  • Slifka MK, Leung DY, Hammarlund E, Raue HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis. J Allergy Clin Immunol. 2014 Feb;133(2):439-47. doi: 10.1016/j.jaci.2013.10.037. Epub 2013 Dec 10.

    PMID: 24331381DERIVED

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, GeneticGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesDermatitisSkin DiseasesSkin and Connective Tissue DiseasesSkin Diseases, EczematousHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Results Point of Contact

Title
Associate Director, Clinical Research Operations Program
Organization
DAIT/NIAID
DAITClinicalTrialsGov@niaid.nih.gov
301-594-7669

Study Officials

  • Jon Hanifin, M.D.

    Oregon Health and Science University

    STUDY CHAIR

  • 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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 25, 2008

First Posted

July 28, 2008

Study Start

August 1, 2008

Primary Completion

April 1, 2011

Study Completion

April 1, 2011

Last Updated

January 13, 2014

Results First Posted

September 30, 2013

Record last verified: 2013-12

Locations

US(3)