Please select the outcome measures that correspond to the clinical trial below.
Title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
Brief Summary: Vitamin A supplementation (VAS) significantly reduces all-cause mortality when given after 6 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal VAS (NNVAS) have produced conflicting findings. These age-pattern variations might result from immunological interactions between VAS and vaccines. The potential efficacy of NNVAS is being retested in 3 large new intervention trials with mortality as endpoint. Complementary mechanistic studies in animals and in human infants in The Gambia (this proposal) and Bangladesh have been commissioned to run in parallel.

The investigators will use a 2-arm double blind RCT to test whether NNVAS modulates the early ontogeny of human immune development. Neonates, recruited through a peri-urban clinic in The Gambia, will receive either 50,000 International Units (IU) VAS 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 (thymic index by ultrasound); 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 and morbidity will also be assessed.


Options:
A: Frequency of circulating Tregs expressing gut homing receptors in infant participants. (17 week post-supplementation)
B: Thymus size measured by ultrasound (through 15 wk of age); peripheral blood naive T-helper lymphocyte concentration (through 15 wk of age); T-cell receptor excision circle (TREC) level in peripheral blood mononuclear cells (PBMC) (through 15 wk of age); T-cell response to BCG (Bacillus Calmette-Guérin; to protect against tuberculosis) and oral polio virus (OPV) immunization (through 15 wk of age); Antibody response to oral polio virus (OPV) immunization (through 15 wk of age); T-cell and antibody response to tetanus toxoid (TT) and hepatitis B virus (HBV) vaccinations given at 6, 10 and 14 wk of age (through 15 wk of age); bacterial translocation to blood (through 15 wk of age)
C: Primary outcome is reduction in Infant Mortality less than six months of age (2 years)
D: Risk of death (Period between receiving the intervention/placebo and six months of age)

Answer: A