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A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study (ELVIS)

Primary Purpose

Innate Immune Response

Status

Completed

Phase

Not Applicable

Locations

Australia

Study Type

Interventional

Intervention

BCG Vaccine

Hepatitis B Vaccine

About this trial

This is an interventional basic science trial for Innate Immune Response focused on measuring neonates, BCG, Hepatitis B vaccine, vaccines, immunity, immune response, Bacille- Calmette-Guerin

Eligibility Criteria

undefined - 3 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
Born no earlier than eight weeks before estimated date of delivery
Birth weight >1500g
Delivered vaginally
Singleton pregnancy

Exclusion Criteria:

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
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

Sites / Locations

Mercy Hospital for Women

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

No Intervention

Arm Label

Group 1

Group 2

Group 3

Group 4

Arm Description

BCG vaccine, 0,05ml intradermally at birth

BCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

No birth vaccines

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02444611

First Posted

April 6, 2015

Last Updated

August 29, 2017

Sponsor

Murdoch Childrens Research Institute

Collaborators

Royal Children's Hospital, Mercy Hospital for Women, Australia

1. Study Identification

Unique Protocol Identification Number

NCT02444611

Brief Title

A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study

Acronym

ELVIS

Official Title

A Randomised, Controlled Trial Investigating the Influence of BCG (Bacillus Calmette-Guérin) and Hepatitis B Immunisation at Birth on Neonatal Immune Responses

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Completed

Study Start Date

March 2015 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

Royal Children's Hospital, Mercy Hospital for Women, Australia

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Innate Immune Response

Keywords

neonates, BCG, Hepatitis B vaccine, vaccines, immunity, immune response, Bacille- Calmette-Guerin

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

185 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Active Comparator

Arm Description

BCG vaccine, 0,05ml intradermally at birth

Arm Title

Group 2

Arm Type

Active Comparator

Arm Description

BCG vaccine, 0,05ml intradermally at birth Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Arm Title

Group 3

Arm Type

Active Comparator

Arm Description

Hepatitis B vaccine, 5 micrograms, intramuscularly at birth

Arm Title

Group 4

Arm Type

No Intervention

Arm Description

No birth vaccines

Intervention Type

Drug

Intervention Name(s)

BCG Vaccine

Other Intervention Name(s)

BCG vaccine- Denmark strain, BCG Denmark, Statens Serum institute BCG vaccine, Mycobacterium bovis BCG vaccine, Danish strain, 1331, Bacillus-Calmette-Guerin

Intervention Description

intradermal vaccination

Intervention Type

Drug

Intervention Name(s)

Hepatitis B Vaccine

Other Intervention Name(s)

HB-Vax-II

Intervention Description

intramuscular vaccination

Primary Outcome Measure Information:

Title

Cytokine concentrations (pg/ml) in response to in-vitro stimulation with a range of antigens

Description

Time Frame

7 (+-4) days post randomisation

10. Eligibility

Sex

All

Maximum Age & Unit of Time

3 Days

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Born no earlier than eight weeks before estimated date of delivery Birth weight >1500g Delivered vaginally Singleton pregnancy Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nigel Curtis, MBBS,PHD

Organizational Affiliation

Royal Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mercy Hospital for Women

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

12. IPD Sharing Statement

Learn more about this trial

A Trial Investigating the Influence of BCG and Hepatitis B Immunisation at Birth on Neonatal Immune Responses: The Early Life Vaccines and Immunity Study

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