A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses (The neonatal Vitamin A Study ‘NNVAS’) NCT01476358
This trial is being run in collaboration with the infant immunology laboratory (Fajara) and the MRC Sukuta field site, at the MRC Unit, The Gambia. This trial is being conducted in human neonates to determine the effect of vitamin A supplementation on immune responses and is one of two mechanistic studies commissioned by WHO (via BMGF funding) to complement three larger RCTs examining all cause mortality following neonatal vitamin A supplementation. The sister mechanistic trial is being run in Bangladesh (principle investigators: Prof. Charles Stephenson, (University of California, Davis) and Dr. Rubhana Raqib, (International Centre for Diarrhoeal Disease Research (ICDDR), Bangladesh).
We are using a 2-arm double blind RCT to test whether NNVAS modulates the early ontogeny of human immune development. Neonates, recruited through the Sukuta Health Centre (a peri-urban clinic in The Gambia), will receive either 50,000 International Units (IU) vitamin A supplementation orally within 48 hours of birth (intervention group, n=100) or a placebo (control group, n=100). Male and female neonates will be randomized separately at enrolment for later analyses by sex. All infants will be followed up from birth to age 1 year. A broad panel of immunological outcomes will examine whether NNVAS: a). normalises thymic development; b). skews mycobacterial and recall antigen responses towards a Th2 profile; c). diminishes Th1 and Th17 reactivity to mycobacterial and recall antigens; d). diminishes the tuberculin skin test (TST) response; e). causes increased innate immune reactivity; f). increases the frequency of circulating regulatory T cells (Tregs) expressing gut homing receptors; g). enhances B cell immune responses after routine vaccination (increase of B cell numbers and activation status); h). increases circulating IgA in mucosal immune compartment, especially oral polio vaccine (OPV) specific IgA post-vaccination; i). decreases bacterial translocation, by improving mucosal barrier function; and j). decreases markers of infection or inflammation. Growth, morbidity, nutritional status, demographic and social economic status will also be assessed.