Clinical trial NCT01476358: Effect of Vitamin A Supplementation on Immune Responses in Human Neonates
Official title: A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Vitamin A Deficiency
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: World Health Organization
First posted: 2011-11-22
Enrollment: 200
Sex: ALL
Minimum age (years): 5
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of circulating Tregs expressing gut homing receptors in infant participants.
timeFrame: 17 week post-supplementation
Secondary outcomes:
measure: Difference in Thymus size in infant participants
timeFrame: 1, 6, 12 and 17 weeks
measure: Difference in B cell immune responses after routine vaccination in infant participants
timeFrame: 6 and 17 weeks
measure: Improved mucosal barrier function in infant participants
timeFrame: 6 and 17 weeks
Other outcomes:
Locations:
city: Fajara
country: Gambia
facility: Medical Research Council, The Gambia Unit
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Suzanna LR McDonald, BSc (Hons) MSc PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McDonald SL, Savy M, Fulford AJ, Kendall L, Flanagan KL, Prentice AM. A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol. BMC Pediatr. 2014 Apr 4;14:92. doi: 10.1186/1471-2431-14-92.