Effect of Vitamin A Supplementation on Immune Responses in Human Neonates
NNVAS
A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
1 other identifier
interventional
200
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2011
CompletedFirst Submitted
Initial submission to the registry
November 9, 2011
CompletedFirst Posted
Study publicly available on registry
November 22, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedNovember 14, 2012
November 1, 2012
1.6 years
November 9, 2011
November 12, 2012
Conditions
Outcome Measures
Primary Outcomes (1)
Frequency of circulating Tregs expressing gut homing receptors in infant participants.
17 week post-supplementation
Secondary Outcomes (3)
Difference in Thymus size in infant participants
1, 6, 12 and 17 weeks
Difference in B cell immune responses after routine vaccination in infant participants
6 and 17 weeks
Improved mucosal barrier function in infant participants
6 and 17 weeks
Study Arms (2)
Vitamin A
ACTIVE COMPARATORCapsule containing oil vehicle with Vitamin A (retinyl palmitate). Capsules are prepared by the manufacturer (Strides Arcolab Limited, India) and assigned blinded codes by World Health Organization officials.
Placebo
PLACEBO COMPARATORCapsule containing oil vehicle withOUT Vitamin A (retinyl palmitate). Capsules are prepared by the manufacturer (Strides Arcolab Limited, India) and assigned blinded codes by World Health Organization officials.
Interventions
Active Comparator (Vitamin A): 1 capsule containing oil carrier and 50,000IU Vitamin A, within 48hs of birth Placebo Comparator: 1 capsule containing oil carrier and 0IU Vitamin A, within 48hs of birth
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Medical Research Council, The Gambia Unit
Fajara, The Gambia
Related Publications (1)
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.
PMID: 24708735DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Suzanna LR McDonald, BSc (Hons) MSc PhD
London School of Hygiene and Tropical Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2011
First Posted
November 22, 2011
Study Start
November 1, 2011
Primary Completion
June 1, 2013
Last Updated
November 14, 2012
Record last verified: 2012-11