Vitamin A Deficiency Clinical Trial
— NNVASOfficial title:
A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
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.
Status | Active, not recruiting |
Enrollment | 200 |
Est. completion date | |
Est. primary completion date | June 2013 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | N/A to 48 Hours |
Eligibility |
Inclusion Criteria: - singleton birth, - birth weight =1,500g, - mother over 18 years willing to participate and residency within the study area. - Birth vaccinations and vitamin A supplement must be administered within 48 hours of birth. Exclusion Criteria: - Infants having a congenital disease, - a serious infection at birth - an inability to feed (initially assessed by the lack of the suck reflex), - mothers who are seriously ill at time of enrolment (defined as bed bound for more than 24 hours), - mother participating in other studies, - mothers who are HIV positive. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Country | Name | City | State |
---|---|---|---|
Gambia | Medical Research Council, The Gambia Unit | Fajara |
Lead Sponsor | Collaborator |
---|---|
London School of Hygiene and Tropical Medicine | World Health Organization |
Gambia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Frequency of circulating Tregs expressing gut homing receptors in infant participants. | 17 week post-supplementation | No | |
Secondary | Difference in Thymus size in infant participants | Assessed by ultrasonic analysis. | 1, 6, 12 and 17 weeks | No |
Secondary | Difference in B cell immune responses after routine vaccination in infant participants | Assessed as an increase in B cell numbers and activation status. | 6 and 17 weeks | No |
Secondary | Improved mucosal barrier function in infant participants | Assessed by quantifying bacterial translocation into the blood. | 6 and 17 weeks | No |
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