Effect of Vitamin A Supplementation on Immune Responses in Human Neonates

NCT ID: NCT01476358

Last Updated: 2012-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Brief Summary

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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.

Detailed Description

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Conditions

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Vitamin A Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vitamin A

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.

Group Type ACTIVE_COMPARATOR

Vitamin A (retinyl palmitate).

Intervention Type DIETARY_SUPPLEMENT

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

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.

Group Type PLACEBO_COMPARATOR

Vitamin A (retinyl palmitate).

Intervention Type DIETARY_SUPPLEMENT

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

Interventions

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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

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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.
Minimum Eligible Age

5 Hours

Maximum Eligible Age

48 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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World Health Organization

OTHER

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Suzanna LR McDonald, BSc (Hons) MSc PhD

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Locations

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Medical Research Council, The Gambia Unit

Fajara, , The Gambia

Site Status

Countries

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The Gambia

References

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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.

Reference Type DERIVED
PMID: 24708735 (View on PubMed)

Other Identifiers

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RPC389

Identifier Type: -

Identifier Source: org_study_id