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

October 25, 2012 updated by: University of Aarhus

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • Department of Infectious Diseases, Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
within 9. month from 1. vaccination

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Within 9 month from 1. vaccination
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
Within 9 month from 1. vaccination
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 .
within 9 month from 1. vaccination
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 .
Within 9. month from 1. vaccination
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
18 month after 1. vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Aarhus University Hospital
Monash Medical Centre

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2011

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2013

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 14, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SJF0001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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