Vitamin A Supplementation With Bacille Calmette Guerin (BCG) Vaccine

NCT ID: NCT00168610

Last Updated: 2013-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

7600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Brief Summary

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In the present study the investigators wish to address the effects of different doses of vitamin A supplementation in low and normal birth weight infants.

Hypotheses:

* Vitamin A supplementation administered at birth together with BCG vaccination is associated with a 30% reduction in infant mortality and morbidity during the first year of life in both normal and low birth weight infants.
* A lower dose of vitamin A may be even more beneficial than a high dose.

Detailed Description

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Vitamin A deficiency is common in low-income countries. Vitamin A supplementation to children above 6 months of age reduces all-cause mortality by 23% to 30%. Studies on vitamin A supplementation in infants younger than 6 months of age have reported inconsistent effects on mortality. Studies providing supplementation between 1 and 5 months of age have found no effect or even a negative effect. However, the only two studies of supplementation at birth, both conducted in Asia, showed substantial significant reductions in infant all-cause mortality.

The beneficial effect of neonatal vitamin A supplementation may be a result of correcting the congenital vitamin A deficiency resulting from maternal vitamin A deficiency. On the other hand, it has been speculated that the beneficial effect of vitamin A supplementation given at birth may in part be explained by a synergistic effect of vitamin A supplementation and BCG vaccination given at the time of birth.

The protective effect on mortality of vitamin A supplementation given at birth needs to be confirmed in an African population. Furthermore, none of the two previous studies have reported data on the vaccination status of the included infants.

In the proposed studies, the effect on mortality and morbidity of giving vitamin A supplementation simultaneously with BCG vaccination at birth to both normal and low birth weight infants will be investigated in an African population. Furthermore, the effects of vitamin A supplementation will be evaluated with respect to effect on growth, the response to BCG vaccination, infant vitamin A status and infant cytokine profile, malaria, measles, rotavirus infection and RSV infection. The mechanisms behind the effects of vitamin A will be evaluated. The potential interactions between vitamin A, sex and vaccines will be taken into account in all analyses.

This will be done in two studies of newborn children. Study A includes 6,000 normal birth weight infants (\> 2500 g) randomized to 50,000 or 25,000 IU vitamin A or placebo given simultaneously with BCG vaccine. Study B includes 1,600 low birth weight infants (\< 2500 g) randomized to vitamin A or placebo and early BCG or late BCG in a two-by-two factorial design. The studies take place in Guinea-Bissau, West Africa. The study area consists of five districts in the capital of Guinea-Bissau. The Bandim Health Project has been working in the study area for almost 25 years, and a demographic surveillance system has been established and has functioned for many years.

Conditions

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Infant Mortality Morbidity

Keywords

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Vitamin A BCG Infant mortality Morbidity Low-income country Mortality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Interventions

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Vitamin A

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Normal birth weight: belonging to the study area
* Low birth weight: being born at the national hospital

Exclusion Criteria

* Overt illness
* Signs of vitamin A deficiency
* Previous BCG vaccination
Maximum Eligible Age

5 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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March of Dimes

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Medical Research Council Unit, The Gambia

OTHER

Sponsor Role collaborator

Bandim Health Project

OTHER

Sponsor Role lead

Principal Investigators

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Peter Aaby

Role: PRINCIPAL_INVESTIGATOR

Bandim Health Project

Locations

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Bandim Health Project, Apartado 861

Bissau, , Guinea-Bissau

Site Status

Countries

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Guinea-Bissau

References

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Schaltz-Buchholzer F, Berendsen M, Roth A, Jensen KJ, Bjerregaard-Andersen M, Kjaer Sorensen M, Monteiro I, Aaby P, Stabell Benn C. BCG skin reactions by 2 months of age are associated with better survival in infancy: a prospective observational study from Guinea-Bissau. BMJ Glob Health. 2020 Sep;5(9):e002993. doi: 10.1136/bmjgh-2020-002993.

Reference Type DERIVED
PMID: 32978212 (View on PubMed)

Schaltz-Buchholzer F, Biering-Sorensen S, Lund N, Monteiro I, Umbasse P, Fisker AB, Andersen A, Rodrigues A, Aaby P, Benn CS. Early BCG Vaccination, Hospitalizations, and Hospital Deaths: Analysis of a Secondary Outcome in 3 Randomized Trials from Guinea-Bissau. J Infect Dis. 2019 Jan 29;219(4):624-632. doi: 10.1093/infdis/jiy544.

Reference Type DERIVED
PMID: 30239767 (View on PubMed)

Benn CS, Martins CL, Fisker AB, Diness BR, Garly ML, Balde I, Rodrigues A, Whittle H, Aaby P. Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau. Vaccine. 2014 Sep 22;32(42):5468-74. doi: 10.1016/j.vaccine.2014.07.090. Epub 2014 Aug 13.

Reference Type DERIVED
PMID: 25131735 (View on PubMed)

Benn CS, Diness BR, Balde I, Rodrigues A, Lausch KR, Martins CL, Fisker AB, Aaby P. Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial. J Nutr. 2014 Sep;144(9):1474-9. doi: 10.3945/jn.114.192674. Epub 2014 Jul 2.

Reference Type DERIVED
PMID: 24991044 (View on PubMed)

Biering-Sorensen S, Fisker AB, Ravn H, Camala L, Monteiro I, Aaby P, Benn CS. The effect of neonatal vitamin A supplementation on growth in the first year of life among low-birth-weight infants in Guinea-Bissau: two by two factorial randomised controlled trial. BMC Pediatr. 2013 May 23;13:87. doi: 10.1186/1471-2431-13-87.

Reference Type DERIVED
PMID: 23702185 (View on PubMed)

Benn CS, Fisker AB, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, Aaby P. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ. 2010 Mar 9;340:c1101. doi: 10.1136/bmj.c1101.

Reference Type DERIVED
PMID: 20215360 (View on PubMed)

Other Identifiers

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6-FY04-51

Identifier Type: -

Identifier Source: secondary_id

6-FY04-51-VITA2

Identifier Type: -

Identifier Source: org_study_id