Hepatitis BNCT01182311
Duration of Long-term Immunity After Hepatitis B Virus Immunization
An observational study of Hepatitis B, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: The hepatitis B vaccine has been shown to be safe and effective in preventing transmission of the hepatitis B virus. Response rates to the initial three doses of the vaccine are high, with significant or even complete immune response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B
- Type of treatment
- Vaccines
- How many people
- 205 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2010to 9 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hospital employees
Who may be able to join
- Age 18 years or above and < 60 years when the first dose of hepatitis B vaccine was administered
- Male or female
- Vaccination with 3 doses of either plasma-derived or recombinant HBV vaccine within one year (with the exception of the 10 patients who were never vaccinated and never infected with the hepatitis B virus)
- Vaccinated subjects must be able to provide written documentation indicating the dates of their hepatitis B immunization series. In the absence of written documentation, subjects will be asked to sign a written affidavit obtained either from themselves or their physician stating the date of vaccination accurate to one year and that they did not receive a booster dose to the best of their knowledge.
- For recovered patients, spontaneous recovery from acute hepatitis B must have occurred prior to the year 2000
- Willing and able to provide written, informed consent
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- Additional Inclusion Criteria for HIV positive cohort
- CD4 count of great than or equal to 250 /mm3 at time of vaccination
- Known HIV infection at time of vaccination
Who cannot join
- History of chronic HBV infection
- Incomplete HBV vaccine doses (with the exception of the 10 patients who were never vaccinated and never infected with the hepatitis B virus)
- Known non-response to an adequate course of hepatitis B vaccine
- Received a booster dose of HBV vaccine
- Current or recent (within the last 1 year) use of immunosuppressive/immuno-modifying agents
- Use of immunosuppressive/immuno-modifying agents at the time of vaccination
Show all 14Show fewer
- Renal failure with requirement for dialysis
- Anti-HIV positive (Except for HIV positive cohort)
- Anti-HCV positive
- History of bone marrow or stem cell transplant
- History of organ transplant
- Known underlying immune suppressive condition
- Subjects with clinically significant anemia, hemoglobin <10g/dL will be excluded from participating in the assessment of response to a booster dose of HBV vaccine until their hemoglobin is greater than or equal to12g/dL.
- Anti-HBc positivity for the 10 patients who were never vaccinated and never infected with the hepatitis B virus.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Duration of Long-Term Immunity After Hepatitis B Virus Immunization
Background:
- The hepatitis B vaccine has been shown to be safe and effective in preventing transmission of the hepatitis B virus. Response rates to the initial three doses of the vaccine are high, with significant or even complete immune response. However, this level has been reported to decline rapidly within the first year and more slowly thereafter. There is little data on the durability and long-term protection provided by the hepatitis B vaccine administered to adults in the United States.
- Vaccinated individuals are believed to be protected against hepatitis B virus infection because of a memory immune response. Even if antibody levels are low, the immune system will still be able to produce enough antibody to neutralize the hepatitis B virus. Therefore, booster doses of the vaccine are not recommended, except for some high-risk individuals such as patients on dialysis. Researchers are interested in determining the durability of the immune response of the hepatitis B vaccine in adults with low or intermediate risk for hepatitis B virus infection.
Read more
Objectives:
- To examine the long-term immune status of human immunodeficiency virus (HIV) positive and negative individuals who received the hepatitis B vaccine during adulthood, compared with the immune status of individuals who acquired natural immunity by recovering from acute hepatitis B during adulthood.
Eligibility:
- Individuals at least 18 years of age who were vaccinated against hepatitis B at least 10 years ago.
- Individuals at least 18 years of age who contracted and recovered from acute hepatitis B at least 10 years ago.
- Individuals at least 18 years of age who have well-controlled HIV and were vaccinated against hepatitis B at least 10 years ago.
Design:
- Participants will have a single outpatient study visit and potential follow-up visits as part of this protocol.
- Participants will complete a questionnaire assessing possible risk factors for hepatitis B infection, and will provide blood samples to test for hepatitis B antibodies and other immune system studies.
- Participants will receive a letter or phone call with the results of the blood tests:
- Those who no longer have protective levels of antibody against the hepatitis B virus will be offered a booster dose of the hepatitis B vaccine. To monitor immune response to the booster vaccine, additional study visits will be scheduled at 1 and 3 weeks following the booster.
- Those who have chronic infection with the hepatitis B virus will be advised to follow up with their primary care physician, and may be eligible to participate in ongoing treatment trials for chronic hepatitis B.
- Those who have abnormal blood tests will be referred back to their primary care physician for investigation of the abnormal tests results, and may also be referred to other National Institutes of Health protocols.
- Additional tests will evaluate immune response to the measles, mumps, and rubella (German measles) viruses. Some participants may be advised to have an additional MMR vaccine through their primary care physician.
Read the detailed description
Hepatitis B vaccine is very effective at preventing infection with the hepatitis B virus (HBV). Several studies have reported on the long-term efficacy of the HBV vaccine and indicate a decline in titers of antibody against hepatitis B surface antigen (anti-HBs) over time. However, most of these studies were performed in persons vaccinated as infants or children. This protocol is designed to examine the long-term immune status of HIV positive and negative individuals who were vaccinated during adulthood, and to compare it to the immune status of individuals who acquired natural immunity by recovering from acute hepatitis B during adulthood. Individuals who lost the vaccine-induced humoral immune response, will be offered a booster vaccination and their immune response to the booster vaccination will be assessed. In this study, we will recruit 150 subjects who were vaccinated secondary to their job-related risk of acquiring HBV infection. An additional 50 subjects who had spontaneously recovered from acute hepatitis B (Bullet) 10 years ago, 50 patients with well-compensated HIV infection who received HBV vaccine (Bullet) 10 years ago and 10 subjects who were never vaccinated and never infected with the hepatitis B virus will be enrolled as comparison groups. All subjects will be asked to complete a questionnaire to assess their HBV exposure risk as well as factors that may affect their immune response. Immunological assays include the quantitation of HBV-specific antibodies and the qualitative and quantitative assessment of HBV-specific memory B cells and T cells at the indicated time intervals after vaccination or after recovery from acute hepatitis B. Additional immunological assays include testing for antibody to measles, mumps and rubella (German measles) viruses to compare the longevity of antibody response to these vaccines or natural infection to the antibody response to the hepatitis B vaccine or natural infection. The results of this study will help to answer the question whether a booster vaccination is required and at which time after the primary vaccination course it should be considered.
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B Virus, Hepatitis B Vaccine, Immunity, B-Cell Response, T-Cell Response, Hepatitis B Immunity, Hepatitis B Virus Vaccine
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Controls | Never received HBV vaccine and never had HBV | |
| HIV vaccinated >= 10 years | Well compensated HIV disease, vaccinated HBV >= 10 years ago | |
| Spontaneously recovered >= 10 years | Spintaneously recovered from acute HBV >= 10 years ago | |
| Vaccinated >= 20 years | Vaccinated against HBV >= 20 years ago | |
| Vaccinated 10 < 15 years | Vaccinated against HBV 10 < 15 years ago | |
| Vaccinated 15 < 20 years | Vaccinated against HBV 15 < 20 years ago |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protective Anti-HBs
Anti-HBs levels >12 mIU/mL
Measured: At start of study
Secondary outcomes (2)
HBV-specific antibodies
Measured: At start of study
Quantitative assessment of HBV-specific memory B cells and T
Measured: At start of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2010 (estimated)
- Study start8 Sep 2010
- Primary completion1 May 2013
- Study completion9 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marc G Ghany, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182311
- Sponsor's protocol ID
- 100187
- Other IDs
- 10-DK-0187
- Status last verified
- Dec 2020
- First submitted
- 13 Aug 2010
- Last updated
- 11 Dec 2020
- Results posted
- No
Publications
Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008 Oct 2;359(14):1486-500. doi: 10.1056/NEJMra0801644. No abstract available.
PubMed 18832247Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009 May;49(5 Suppl):S28-34. doi: 10.1002/hep.22975.
PubMed 19399791McQuillan GM, Coleman PJ, Kruszon-Moran D, Moyer LA, Lambert SB, Margolis HS. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health. 1999 Jan;89(1):14-8. doi: 10.2105/ajph.89.1.14.
PubMed 9987458Gara N, Abdalla A, Rivera E, Zhao X, Werner JM, Liang TJ, Hoofnagle JH, Rehermann B, Ghany MG. Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults. Clin Infect Dis. 2015 Feb 15;60(4):505-13. doi: 10.1093/cid/ciu867. Epub 2014 Nov 10.
PubMed 25389254
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Duration of Long-Term Immunity After Hepatitis B Virus Immunization
- ClinicalTrials.gov ID
- NCT01182311
- Acronym / sponsor ID
- 100187
- Conditions
- Hepatitis B
- Keywords
- Hepatitis B Virus, Hepatitis B Vaccine, Immunity, B-Cell Response, T-Cell Response, Hepatitis B Immunity, Hepatitis B Virus Vaccine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 8 Sep 2010 (actual)
- Primary completion
- 1 May 2013 (actual)
- Study completion
- 9 Dec 2020 (actual)
- First posted
- 16 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- The hepatitis B vaccine has been shown to be safe and effective in preventing transmission of the hepatitis B virus. Response rates to the initial three doses of the vaccine are high, with significant or even complete immune response. However, this level has been reported to decline rapidly within the first year and more slowly thereafter. There is little data on the durability and long-term protection provided by the hepatitis B vaccine administered to adults in the United States.
- Vaccinated individuals are believed to be protected against hepatitis B virus infection because of a memory immune response. Even if antibody levels are low, the immune system will still be able to produce enough antibody to neutralize the hepatitis B virus. Therefore, booster doses of the vaccine are not recommended, except for some high-risk individuals such as patients on dialysis. Researchers are interested in determining the durability of the immune response of the hepatitis B vaccine in adults with low or intermediate risk for hepatitis B virus infection.
Objectives:
- To examine the long-term immune status of human immunodeficiency virus (HIV) positive and negative individuals who received the hepatitis B vaccine during adulthood, compared with the immune status of individuals who acquired natural immunity by recovering from acute hepatitis B during adulthood.
Eligibility:
- Individuals at least 18 years of age who were vaccinated against hepatitis B at least 10 years ago.
- Individuals at least 18 years of age who contracted and recovered from acute hepatitis B at least 10 years ago.
- Individuals at least 18 years of age who have well-controlled HIV and were vaccinated against hepatitis B at least 10 years ago.
Design:
- Participants will have a single outpatient study visit and potential follow-up visits as part of this protocol.
- Participants will complete a questionnaire assessing possible risk factors for hepatitis B infection, and will provide blood samples to test for hepatitis B antibodies and other immune system studies.
- Participants will receive a letter or phone call with the results of the blood tests:
- Those who no longer have protective levels of antibody against the hepatitis B virus will be offered a booster dose of the hepatitis B vaccine. To monitor immune response to the booster vaccine, additional study visits will be scheduled at 1 and 3 weeks following the booster.
- Those who have chronic infection with the hepatitis B virus will be advised to follow up with their primary care physician, and may be eligible to participate in ongoing treatment trials for chronic hepatitis B.
- Those who have abnormal blood tests will be referred back to their primary care physician for investigation of the abnormal tests results, and may also be referred to other National Institutes of Health protocols.
- Additional tests will evaluate immune response to the measles, mumps, and rubella (German measles) viruses. Some participants may be advised to have an additional MMR vaccine through their primary care physician.
Detailed description
Hepatitis B vaccine is very effective at preventing infection with the hepatitis B virus (HBV). Several studies have reported on the long-term efficacy of the HBV vaccine and indicate a decline in titers of antibody against hepatitis B surface antigen (anti-HBs) over time. However, most of these studies were performed in persons vaccinated as infants or children. This protocol is designed to examine the long-term immune status of HIV positive and negative individuals who were vaccinated during adulthood, and to compare it to the immune status of individuals who acquired natural immunity by recovering from acute hepatitis B during adulthood. Individuals who lost the vaccine-induced humoral immune response, will be offered a booster vaccination and their immune response to the booster vaccination will be assessed. In this study, we will recruit 150 subjects who were vaccinated secondary to their job-related risk of acquiring HBV infection. An additional 50 subjects who had spontaneously recovered from acute hepatitis B (Bullet) 10 years ago, 50 patients with well-compensated HIV infection who received HBV vaccine (Bullet) 10 years ago and 10 subjects who were never vaccinated and never infected with the hepatitis B virus will be enrolled as comparison groups. All subjects will be asked to complete a questionnaire to assess their HBV exposure risk as well as factors that may affect their immune response. Immunological assays include the quantitation of HBV-specific antibodies and the qualitative and quantitative assessment of HBV-specific memory B cells and T cells at the indicated time intervals after vaccination or after recovery from acute hepatitis B. Additional immunological assays include testing for antibody to measles, mumps and rubella (German measles) viruses to compare the longevity of antibody response to these vaccines or natural infection to the antibody response to the hepatitis B vaccine or natural infection. The results of this study will help to answer the question whether a booster vaccination is required and at which time after the primary vaccination course it should be considered.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Controls | – | –Never received HBV vaccine and never had HBV |
| HIV vaccinated >= 10 years | – | –Well compensated HIV disease, vaccinated HBV >= 10 years ago |
| Spontaneously recovered >= 10 years | – | –Spintaneously recovered from acute HBV >= 10 years ago |
| Vaccinated >= 20 years | – | –Vaccinated against HBV >= 20 years ago |
| Vaccinated 10 < 15 years | – | –Vaccinated against HBV 10 < 15 years ago |
| Vaccinated 15 < 20 years | – | –Vaccinated against HBV 15 < 20 years ago |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospital employees
Key inclusion criteria (9 listed)
- Additional Inclusion Criteria for HIV positive cohort
- CD4 count of great than or equal to 250 /mm3 at time of vaccination
- Known HIV infection at time of vaccination
Key exclusion criteria (14 listed)
- History of chronic HBV infection
- Incomplete HBV vaccine doses (with the exception of the 10 patients who were never vaccinated and never infected with the hepatitis B virus)
- Known non-response to an adequate course of hepatitis B vaccine
- Received a booster dose of HBV vaccine
- Current or recent (within the last 1 year) use of immunosuppressive/immuno-modifying agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Protective Anti-HBs
Time frame: At start of study
Anti-HBs levels >12 mIU/mL
2 secondary outcomes
HBV-specific antibodies
Time frame: At start of study
Quantitative assessment of HBV-specific memory B cells and T
Time frame: At start of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2020.
- Background: PubMed 18832247Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008 Oct 2;359(14):1486-500. doi: 10.1056/NEJMra0801644. No abstract available.
- Background: PubMed 19399791Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009 May;49(5 Suppl):S28-34. doi: 10.1002/hep.22975.
- Background: PubMed 9987458McQuillan GM, Coleman PJ, Kruszon-Moran D, Moyer LA, Lambert SB, Margolis HS. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health. 1999 Jan;89(1):14-8. doi: 10.2105/ajph.89.1.14.
- Derived from this study: PubMed 25389254Gara N, Abdalla A, Rivera E, Zhao X, Werner JM, Liang TJ, Hoofnagle JH, Rehermann B, Ghany MG. Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults. Clin Infect Dis. 2015 Feb 15;60(4):505-13. doi: 10.1093/cid/ciu867. Epub 2014 Nov 10.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc G Ghany, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Protective Anti-HBs (time frame: At start of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01182311, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2020.