Condition category
Neonatal Diseases
Date applied
25/07/2013
Date assigned
03/09/2013
Last edited
03/09/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Bacillus-Calmette Guerin (BCG) vaccination is given to babies at birth to protect them against tuberculosis (TB). There is some evidence that this vaccination might also protect infants against other infections, but it is not known how this might happen. Our aim is to find out whether BCG vaccination might decrease iron levels in the blood stream. As iron is very
important for the growth of many infectious diseases, such a reduction might limit the growth of these organisms. This might therefore provide babies with protection against many serious diseases. This study is a small initial study to compare the levels of iron and its controlling hormone in BCG vaccinated and unvaccinated babies in the first few days of life. The results of this study will be used to design future research.

Who can participate?
Any healthy baby born and registered in the study area (West Kiang, The Gambia) is free to participate. They can only be included in the study if they are seen within the first 24 hours of life and consent is gained from the mother.

What does the study involve?
Babies participating in the study will be randomly assigned to receive BCG vaccination either on the first day of life or delayed to 24-96 hours of age. All infants will have two blood tests taken, one immediately after birth (before any vaccinations are given) and a second at either 24 or 72 hours after the first blood test. Any child receiving delayed BCG vaccination will then be vaccinated following their second blood test. All infants will receive all other routine vaccinations as normal at birth. A medical professional will clinically review all infants at the time of their blood tests. Any child deemed to be unwell will be referred to the research clinic for treatment. Each infant’s study involvement will be complete by 4 days of age. The blood samples taken from each infant will be tested for markers of iron status, as well as for levels of the hormone regulating iron status.

What are the possible benefits and risks of participating?
Participants benefit from early review by trained medical professionals in their homes. Any unwell child will be transferred directly to receive medical attention free of charge. Participants also benefit by receiving vaccinations earlier than they otherwise would. There is a very small increased risk of tuberculosis infection in infants who have delayed BCG vaccination compared to those that receive it on the first day of life. This is minimised by excluding infants born into families with a known case of active TB. The very short delay in vaccination also makes the risk of infection minimal. The taking of two blood samples from participants is likely to cause a small amount of discomfort. This will be minimised by comfort measures such as breast-feeding. Blood sampling also poses a potential risk of introducing infection to the baby. This will be minimised by making sure all procedures are carried out in a sterile way. The volume of blood taken at each of the blood tests is well within recommended guidelines and should not pose any risk to infants.

Where is the study run from?
This study is run from the MRC-Keneba field station in The Gambia.

When is the study starting and how long is it expected to run for?
The study started in June 2013 and is expected to last for 6 months. It will continue until 80 infants (40 male and 40 female) have been recruited.

Who is funding the study?
The study is funded by the Medical Research Council, UK.

Who is the main contact?
Dr Sarah Prentice, Sarah.prentice@lshtm.ac.uk
Dr Sophie Moore, Sophie.moore@lshtm.ac.uk
Dr Rita Wegmuller, rwegmuller@mrc.gm

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sarah Prentice

ORCID ID

Contact details

London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom
sarah.prentice@lshtm.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

SCC 1325v2

Study information

Scientific title

Does neonatal BCG (Bacillus of Calmette and Guerin) vaccination elicit an acute hepcidin-mediated Hypoferremia: a pilot randomised controlled trial

Acronym

BCG-Hypo

Study hypothesis

We hypothesise that the inflammation stimulated by BCG vaccination of neonates causes a reduction in serum iron by enhancing the IL-6 (interleukin-6) driven production of hepcidin. We further hypothesise that this reduction of serum iron produces protection against heterologous pathogens (though this will not be tested in this pilot study).The null hypothesis is that there will be no difference in serum iron status and the inflammatory-iron axis at 24 hours and 72 hours of age between BCG vaccinated and unvaccinated individuals.

Ethics approval

1. Joint Gambia Government/MRC Unit The Gambia Ethics Committee
2. The London School of Hygiene and Tropical Medicine Ethics Committee

Study design

Pilot un-blinded randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

The effect of BCG vaccination on serum iron status in neonates

Intervention

BCG-Danish 0.05ml Intra-dermally. Subjects randomised to receive BCG vaccination on the first day of life (<24 hours of age) or delayed to following their second blood test (24-96 hours of age). Follow-up is until 4 days of age. Children are clinically assessed by a paediatrician/nurse at each blood sample visit during this time (twice). There is no current longer term follow-up.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. Plasma transferrin saturation
2. Plasma hepcidin level: ELISA - Bachem-25
3. Plasma IL-6 level: ELISA

All outcomes will be measured at baseline (cord blood), <24 hours of age and at either 24 (+/- 4 hours) or 72 hours (+/- 4 hours) from the time of the first venous blood sample. The timing of the second sample (24 or 72 hours) is randomly assigned.

Secondary outcome measures

1. Serum iron
2. Serum Unbound Iron Binding Capacity
3. Ferritin
4. Transferrin
5. Red cell parameters (haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscle haemoglobin concentration, haematocrit, red cell distribution width, red blood cell count) measured by Automated Analyser (Medonic)
Iron parameters are measured by Automated Cobas Analyser (Roche).

Overall trial start date

17/06/2013

Overall trial end date

17/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Neonates seen within the first 24 hours of age
2. Neonates resident in West Kiang, The Gambia and enrolled in the West Kiang Demographic Surveillance System

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

80

Participant exclusion criteria

1. Neonates with birth weight less than 2000g
2. Neonates with severe birth asphyxia
3. Neonates with major congenital malformations
4. Neonates born to mothers with known HIV or active tuberculosis
5. Neonates born into families with a known active case of tuberculosis in the same compound
6. Neonates currently enrolled in another research study.

Recruitment start date

17/06/2013

Recruitment end date

17/12/2013

Locations

Countries of recruitment

Gambia

Trial participating centre

London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom

Sponsor information

Organisation

Medical Research Council (UK)

Sponsor details

14th Floor
One Kemble Street
London
WC2B 4AN
United Kingdom
firstname.lastname@mrc.ac.uk

Sponsor type

Research council

Website

http://www.mrc.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC), UK. Grant number: MC-A760-5QX00

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes