Innate Immune ResponseELVISNCT02444611
A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study
A study testing BCG Vaccine and Hepatitis B Vaccine in people with Innate Immune Response, run by Murdoch Childrens Research Institute at 1 site in Australia.
Trial summary
Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood disease-specific immunisation is irrefutably linked to the decline in deaths from these targeted infections over the last century. Read more about this study
- Who is it for?
- Ages Up to 3 days
- Conditions the study is for
- Innate Immune Response
- What is being tested?
- BCG Vaccine and Hepatitis B Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2015to Jun 2016
- Phase
- Interventional
- 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 Up to 3 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- English speaking parent
- Planned travel to a TB (Tuberculosis) endemic country within the infant's first 5 years of life
- An informed consent form must be signed and dated by the infant's mother after the nature of the study has been explained and prior to any study assessments/procedures
- The infant's mother has screened negative for HIV during this pregnancy
- The infant's mother has screened negative for Hepatitis B during this pregnancy
- There is no known household contact infected with Hepatitis B
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- Born no earlier than eight weeks before estimated date of delivery
- Birth weight >1500g
- Delivered vaginally
- Singleton pregnancy
Who cannot join
- Known or suspected HIV infection
- Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor---alpha (TNF---alpha) (e.g. infliximab, etanercept, adalimumab).
- Born to a mother treated with bDMARDs (biological Disease- Modifying Anti-Rheumatic drugs) (e.g. TNF---alpha blocking monoclonal antibodies) in the 3rd trimester
- Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway
- Malignancies involving bone marrow or lymphoid systems
- Serious underlying illness including severe malnutrition
Show all 16Show fewer
- Medically unstable
- Generalised septic skin disease and skin conditions such as eczema, dermatitis and psoriasis
- Significant febrile illness
- Also excluded are infants with:
- A mother who is immunosuppressed;
- A mother who has received Intravenous immunoglobulins during her pregnancy
- A family history of immunodeficiency;
- Consanguineous parents.
- Mother who is having a planned Caesarean Section
- A home address more than 40 minutes drive from the Mercy hospital for Women and are unwilling to return to hospital for infant blood sampling
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Controlled Trial Investigating the Influence of BCG (Bacillus Calmette-Guérin) and Hepatitis B Immunisation at Birth on Neonatal Immune Responses
Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood disease-specific immunisation is irrefutably linked to the decline in deaths from these targeted infections over the last century. However, neonatal immunisation is limited, in part, by the impaired adaptive immune function in this age group.
There is now an expanding body of evidence for heterologous ('non-specific') effects of various vaccines used in childhood. This refers to the immunomodulatory capabilities of vaccines to influence immune outcomes beyond the vaccine's specific targeted disease. The underlying immunological mechanisms responsible for these effects are incompletely understood, but evidence is mounting that the innate immune system is central to these observed effects.
Read more
This study is a randomised controlled trial designed to determine the influence of two commonly administered neonatal immunisations, BCG and Hepatitis B vaccine, given at birth, on the neonatal immune responses to non-specific antigens.
The investigators will recruit 200 newborns at the Mercy Hospital for Women in Melbourne, Australia over a 1-year period. These babies will be allocated randomly to one of 4 groups, receiving these 2 vaccines in different combinations, at 2 set time points. (at birth and 1 week post randomisation) A blood sample will be taken at 1-week post randomisation for in vitro immunological analyses.
This study will improve current understanding of the influence of vaccines on neonatal immunity and will help develop strategies exploiting beneficial heterologous ('non-specific') effects to improve protection against infection in the very young.
- Conditions
- Innate Immune Response
- Being tested
- BCG Vaccine, Hepatitis B Vaccine
- Keywords
- neonates, BCG, Hepatitis B vaccine, vaccines, immunity, immune response, Bacille- Calmette-Guerin
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG VaccineDrug
Also called BCG vaccine- Denmark strain, BCG Denmark, Statens Serum institute BCG vaccine, Mycobacterium bovis BCG vaccine, Danish strain, 1331
intradermal vaccination
Hepatitis B VaccineDrug
Also called HB-Vax-II
intramuscular vaccination
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | BCG vaccine, 0,05ml intradermally at birth Receives: Drug: BCG Vaccine |
| Group 2 | Active comparator | BCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth Receives: Drug: BCG Vaccine; Drug: Hepatitis B Vaccine |
| Group 3 | Active comparator | Hepatitis B vaccine, 5 micrograms, intramuscularly at birth Receives: Drug: Hepatitis B Vaccine |
| Group 4 | No intervention | No birth vaccines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens
Four hours after blood samples are collected, they will be stimulated with different concentrations of infective antigens for 20hrs. (eg killed S.aureus, S. pneumoniae, E. Coli, Haemophilus Influenza B, Group B streptococcus, C. albicans), BCG, Hepatitis B sAg). Cytokine expression will be analysed in supernatants by Luminex -based multiplex assays.
The cytokines that will be measured:
Interleukin-1 beta, Interleukin-1ra, Interleukin-6, Interleukin-8, Macrophage/Monocyte Chemoattractant Protein-1(MCP-1), Macrophage Inflammatory Protein (MIP) -1 alpha, MIP-1 beta, Interferon(IFN) gamma, Interleukin-10, Macrophage migration inhibitory factor (MIF), Monokine induced by interferon (MIG), Tumour necrosis factor (TNF) alpha
Measured: 7 (+-4) days post randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2015 (estimated)
- Study startMar 2015
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Innate Immune ResponseStudies of the same condition, open and under way.
- More trials run by Murdoch Childrens Research InstituteThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- Murdoch Childrens Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Children's Hospital, Mercy Hospital for Women, Australia
- Responsible party
- Principal investigator, Prof Nigel Curtis, Murdoch Childrens Research Institute
- Investigators
- Nigel Curtis, MBBS,PHD, Principal investigator, Royal Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02444611
- Sponsor's protocol ID
- VAC/01 ELVIS
- Acronym
- ELVIS
- Status last verified
- Aug 2017
- First submitted
- 6 Apr 2015
- Last updated
- 31 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Controlled Trial Investigating the Influence of BCG (Bacillus Calmette-Guérin) and Hepatitis B Immunisation at Birth on Neonatal Immune Responses
- ClinicalTrials.gov ID
- NCT02444611
- Acronym / sponsor ID
- ELVIS / VAC/01 ELVIS
- Conditions
- Innate Immune Response
- Keywords
- neonates, BCG, Hepatitis B vaccine, vaccines, immunity, immune response, Bacille- Calmette-Guerin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- Murdoch Childrens Research InstituteUniversity, hospital or other
- Collaborators
- Royal Children's Hospital, Mercy Hospital for Women, Australia
- Study start
- Mar 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 14 May 2015 (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.
Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood disease-specific immunisation is irrefutably linked to the decline in deaths from these targeted infections over the last century. However, neonatal immunisation is limited, in part, by the impaired adaptive immune function in this age group.
There is now an expanding body of evidence for heterologous ('non-specific') effects of various vaccines used in childhood. This refers to the immunomodulatory capabilities of vaccines to influence immune outcomes beyond the vaccine's specific targeted disease. The underlying immunological mechanisms responsible for these effects are incompletely understood, but evidence is mounting that the innate immune system is central to these observed effects.
This study is a randomised controlled trial designed to determine the influence of two commonly administered neonatal immunisations, BCG and Hepatitis B vaccine, given at birth, on the neonatal immune responses to non-specific antigens.
The investigators will recruit 200 newborns at the Mercy Hospital for Women in Melbourne, Australia over a 1-year period. These babies will be allocated randomly to one of 4 groups, receiving these 2 vaccines in different combinations, at 2 set time points. (at birth and 1 week post randomisation) A blood sample will be taken at 1-week post randomisation for in vitro immunological analyses.
This study will improve current understanding of the influence of vaccines on neonatal immunity and will help develop strategies exploiting beneficial heterologous ('non-specific') effects to improve protection against infection in the very young.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: BCG VaccineBCG vaccine, 0,05ml intradermally at birth |
| Group 2 | Active comparator | Drug: BCG Vaccine, Drug: Hepatitis B VaccineBCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth |
| Group 3 | Active comparator | Drug: Hepatitis B VaccineHepatitis B vaccine, 5 micrograms, intramuscularly at birth |
| Group 4 | No intervention | –No birth vaccines |
Who may qualify
- Ages
- Up to 3 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- English speaking parent
- Planned travel to a TB (Tuberculosis) endemic country within the infant's first 5 years of life
- An informed consent form must be signed and dated by the infant's mother after the nature of the study has been explained and prior to any study assessments/procedures
- The infant's mother has screened negative for HIV during this pregnancy
- The infant's mother has screened negative for Hepatitis B during this pregnancy
Key exclusion criteria (16 listed)
- Known or suspected HIV infection
- Treatment with corticosteroids or other immunosuppressive therapy, including monoclonal antibodies against tumour necrosis factor---alpha (TNF---alpha) (e.g. infliximab, etanercept, adalimumab).
- Born to a mother treated with bDMARDs (biological Disease- Modifying Anti-Rheumatic drugs) (e.g. TNF---alpha blocking monoclonal antibodies) in the 3rd trimester
- Congenital cellular immunodeficiencies including specific deficiencies of the interferon gamma pathway
- Malignancies involving bone marrow or lymphoid systems
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG VaccineAlso: BCG vaccine- Denmark strain, BCG Denmark, Statens Serum institute BCG vaccine, Mycobacterium bovis BCG vaccine, Danish strain, 1331intradermal vaccination | Drug | Group 1, Group 2 |
| Hepatitis B VaccineAlso: HB-Vax-IIintramuscular vaccination | Drug | Group 2, Group 3 |
Primary outcome
Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens
Time frame: 7 (+-4) days post randomisation
Four hours after blood samples are collected, they will be stimulated with different concentrations of infective antigens for 20hrs. (eg killed S.aureus, S. pneumoniae, E. Coli, Haemophilus Influenza B, Group B streptococcus, C. albicans), BCG, Hepatitis B sAg). Cytokine expression will be analysed in supernatants by Luminex -based multiplex assays. The cytokines that will be measured: Interleukin-1 beta, Interleukin-1ra, Interleukin-6, Interleukin-8, Macrophage/Monocyte Chemoattractant Protein-1(MCP-1), Macrophage Inflammatory Protein (MIP) -1 alpha, MIP-1 beta, Interferon(IFN) gamma, Interleukin-10, Macrophage migration inhibitory factor (MIF), Monokine induced by interferon (MIG), Tumour necrosis factor (TNF) alpha
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 31 Aug 2017.
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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.
Nigel Curtis, MBBS,PHD principal investigator
Royal Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BCG Vaccine and Hepatitis B Vaccine in people with Innate Immune Response, run by Murdoch Childrens Research Institute at 1 site in Australia.
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 10 inclusion and 16 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 31 Aug 2017. 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 Australia. 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?
Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens (time frame: 7 (+-4) days post randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Aug 2017.