Overview

This trial is active, not recruiting.

Condition vitamin a deficiency
Treatment vitamin a (retinyl palmitate).
Phase phase 2
Sponsor London School of Hygiene and Tropical Medicine
Collaborator World Health Organization
Start date November 2011
End date June 2013
Trial size 200 participants
Trial identifier NCT01476358, RPC389

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Arm
(Active Comparator)
Capsule 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.
vitamin a (retinyl palmitate).
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
(Placebo Comparator)
Capsule 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.
vitamin a (retinyl palmitate).
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

Primary Outcomes

Measure
Frequency of circulating Tregs expressing gut homing receptors in infant participants.
time frame: 17 week post-supplementation

Secondary Outcomes

Measure
Difference in Thymus size in infant participants
time frame: 1, 6, 12 and 17 weeks
Difference in B cell immune responses after routine vaccination in infant participants
time frame: 6 and 17 weeks
Improved mucosal barrier function in infant participants
time frame: 6 and 17 weeks

Eligibility Criteria

Male or female participants up to 48 hours old.

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.

Additional Information

Official title A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses
Principal investigator Suzanna LR McDonald, BSc (Hons) MSc PhD
Trial information was received from ClinicalTrials.gov and was last updated in November 2012.
Information provided to ClinicalTrials.gov by London School of Hygiene and Tropical Medicine.