- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00168610
Vitamin A Supplementation With Bacille Calmette Guerin (BCG) Vaccine
Should Infants Receive High-dose Vitamin A Supplementation With BCG Vaccine at Birth in Developing Countries? Randomized Prospective Studies in Guinea-Bissau
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Bissau, Guinea-Bissau
- Bandim Health Project, Apartado 861
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Mortality
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Morbidity
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Secondary Outcome Measures
Outcome Measure |
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Growth
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Adverse effects
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Tuberculin reaction
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BCG scarring
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Vitamin A status
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Cytokine responses
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Malaria
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Measles
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Rotavirus
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Respiratory syncytial virus (RSV) infection
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All primary and secondary outcomes will be analysed for interactions between vitamin A and sex and last vaccine received.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Peter Aaby, Bandim Health Project
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 6-FY04-51-VITA2
- 6-FY04-51
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