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Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders

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ClinicalTrials.gov Identifier: NCT01451801
Recruitment Status : Unknown
Verified October 2012 by University of Aarhus.
Recruitment status was:  Active, not recruiting
First Posted : October 14, 2011
Last Update Posted : October 26, 2012
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Previous studies have shown that 5-10% of Hepatitis B Virus vaccine recipients produce none or to few antibodies after a standard immunization with 3 vaccines. These individuals are defined as non-responders. The investigators wish to investigate if mounting another kind of immune response, called the cellular immune (CMI) response, protects these non-responders.

Aim/Hypothesis

Primary aims:

  1. To estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization

    Secondary aims:

  2. To establish the prevalence of serological non-responders after a standard course of HBV vaccination.
  3. To assess the safety of the vaccine.
  4. Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization
  5. To compare the immunological profile before and after a standard HBV vaccination regimen on non-responders and responders
  6. Establish a rapid test for measuring CMI after being HBV vaccinated.

A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months. Blood is drawn at 0 and 8 months from all participants. The blood will be analysed to see if there is antibodies or/and if there is mounted a cellular immune response by measuring on parameters called cytokines.


Condition or disease Intervention/treatment Phase
Hepatitis B Biological: Twinrix Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Cellular Immunity in Adult Hepatitis B-vaccinated Serologic Non-responders
Study Start Date : October 2011
Estimated Primary Completion Date : July 2013
Estimated Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
HBsAg Biological: Twinrix

A total of 400 healthy volunteers receive a standard course of immunization with a combined hepatitis A and B vaccine (Twinrix®) at 0, 1, and 6 months.

Twinrix ® Adult suspension for injection. 1 ml contains 720 ELISA units of hepatitis A virus antigen adsorbed to aluminum hydroxide and 20 micrograms hepatitis B surface antigen (HBsAg) adsorbed to aluminum phosphate in sterile water. Excipient: sodium chloride. Contains traces of neomycin.



Outcome Measures

Primary Outcome Measures :
  1. Estimate the CMI response in serologic non-responders after receiving a standard course of HBV immunization [ Time Frame: within 9. month from 1. vaccination ]
    Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells


Secondary Outcome Measures :
  1. Establish the prevalence of serological non-responders after a standard course of HBV vaccination defined by anti-HBs <10 mIU / ml [ Time Frame: Within 9 month from 1. vaccination ]
    Antibodies to Hepatitis B surface antigen are detected by use of a comercially available kit at the department of Clinical Immunology, Aarhus University Hospital, Skejby

  2. Assess the safety of the vaccine by evaluating the numbers and intensity of adverse and Serious adverse events [ Time Frame: Within 9 month from 1. vaccination ]
    By evaluating adverse events described in Case Report Forms

  3. Evaluate predictors of serologic non-response in young, healthy individuals receiving a standard course of HBV immunization [ Time Frame: within 9 month from 1. vaccination ]
    Questionnaire and *Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells *HBsAg-specific T cell proliferation is quantified*The difference in phenotypic T cell profiles is getting compared at baseline*HBsAg-specific B cells measured by flow cytometry with staining for surface markers*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .

  4. Compare the immunological profile before and after a standard HBV vaccination regimen, with com-parison of serological non-responders and serological responders [ Time Frame: Within 9. month from 1. vaccination ]
    Magnitude of HBsAg-specific cell-mediated immune response.The presence of antigen specifik single, double or triple cytokine-producing T cells. Numbers and fractions of antigen-specific CD4 and CD8 T cells *HBsAg-specific T cell proliferation is quantified*The difference in phenotypic T cell profiles is getting compared at baseline*HBsAg-specific B cells measured by flow cytometry with staining for surface markers*Supernatant from HBsAg-stimulated PBMC is analysed regarding cytokines* Production of pro- og antiinflammatory cytokines is assesed by RT-PCR .

  5. Establish a rapid test for measuring HBsAg specific CMI by use of an IFN-gamma based assay. [ Time Frame: 18 month after 1. vaccination ]
    Preparation of peripheral blood mononuclear cells (PBMC) Optimisation of antigen-specific cytokine flow cytometry Quantification of IFN-γ producing CD4+ T cells


Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed participant information and consent
  • Age over 18 years
  • Women of childbearing potential must use effective contraceptives

Exclusion Criteria:

  • previous HBV infection
  • previous HBV immunization
  • pregnancy (or planned pregnancy within 6 months)
  • allergy to contents in the vaccine (formaldehyde).
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): NCT01451801


Locations
Denmark
Department of Infectious Diseases, Aarhus University Hospital
Aarhus N, Denmark, 8200
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital
Monash Medical Centre
Investigators
Study Chair: Lars Østergaard, Head Department of Infectious Diseases, Aarhus University Hospital
Study Director: Søren Jensen-Fangel, MD Department of Infectious Diseases, Aarhus University Hospital
Study Director: Martin Tolstrup, MSc Department of Infectious Diseases, Aarhus University Hospital
Principal Investigator: Maria B Pedersen, Bach.Med Department of Infectious Diseases, Aarhus University Hospital
More Information

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01451801     History of Changes
Other Study ID Numbers: SJF0001
First Posted: October 14, 2011    Key Record Dates
Last Update Posted: October 26, 2012
Last Verified: October 2012

Keywords provided by University of Aarhus:
Hepatitis B
non responders
cellular immune response
cytokines
predictors
HBsAg

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections