Effect of Vitamin A Supplementation on Immune Responses in Human Neonates
Information source: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Vitamin A Deficiency
Intervention: Vitamin A (retinyl palmitate). (Dietary Supplement)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: London School of Hygiene and Tropical Medicine
Official(s) and/or principal investigator(s):
Suzanna LR McDonald, BSc (Hons) MSc PhD, Principal Investigator, Affiliation: London School of Hygiene and Tropical Medicine
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.
Official title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary outcome: Frequency of circulating Tregs expressing gut homing receptors in infant participants.
Difference in Thymus size in infant participants
Difference in B cell immune responses after routine vaccination in infant participants
Improved mucosal barrier function in infant participants
Minimum age: N/A.
Maximum age: 48 Hours.
- 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
- 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.
Locations and Contacts
Medical Research Council, The Gambia Unit, Fajara, Gambia
Starting date: November 2011
Last updated: November 12, 2012