Clinical Trial: Effect of Vitamin A Supplementation on Immune Responses in Human Neonates

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official 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 mucosa

Detailed Summary:
Sponsor: London School of Hygiene and Tropical Medicine

Current Primary Outcome: Frequency of circulating Tregs expressing gut homing receptors in infant participants. [ Time Frame: 17 week post-supplementation ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Difference in Thymus size in infant participants [ Time Frame: 1, 6, 12 and 17 weeks ]
    Assessed by ultrasonic analysis.
  • Difference in B cell immune responses after routine vaccination in infant participants [ Time Frame: 6 and 17 weeks ]
    Assessed as an increase in B cell numbers and activation status.
  • Improved mucosal barrier function in infant participants [ Time Frame: 6 and 17 weeks ]
    Assessed by quantifying bacterial translocation into the blood.


Original Secondary Outcome: Same as current

Information By: London School of Hygiene and Tropical Medicine

Dates:
Date Received: November 9, 2011
Date Started: November 2011
Date Completion:
Last Updated: November 12, 2012
Last Verified: November 2012