Vitamin A Supplementation With Bacille Calmette Guerin (BCG) Vaccine

Morbidity Clinical Trial

Official title:

Should Infants Receive High-dose Vitamin A Supplementation With BCG Vaccine at Birth in Developing Countries? Randomized Prospective Studies in Guinea-Bissau

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00168610
• Other study ID #: 6-FY04-51-VITA2
• Secondary ID: 6-FY04-51
• Status: Active, not recruiting
• Phase: Phase 4
• First received: September 9, 2005
• Last updated: November 14, 2013
• Start date: November 2004

Study information

• Verified date: November 2013
• Source: Bandim Health Project
• Contact: n/a
• Is FDA regulated: No
• Health authority: Guinea-Bissau: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7600
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 5 Months

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Infant Mortality
• Morbidity

Intervention

Drug:
• Vitamin A

Locations

Country	Name	City	State
Guinea-Bissau	Bandim Health Project, Apartado 861	Bissau

Sponsors (4)

Lead Sponsor	Collaborator
Bandim Health Project	Leiden University Medical Center, March of Dimes, Medical Research Council Unit, The Gambia

Country where clinical trial is conducted

Guinea-Bissau, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality
Primary	Morbidity
Secondary	Adverse effects
Secondary	Tuberculin reaction
Secondary	BCG scarring
Secondary	Growth
Secondary	Vitamin A status
Secondary	Cytokine responses
Secondary	Malaria
Secondary	Measles
Secondary	Rotavirus
Secondary	Respiratory syncytial virus (RSV) infection
Secondary	All primary and secondary outcomes will be analysed for interactions between vitamin A and sex and last vaccine received.