Effect of Vitamin A Supplementation on Immune Responses in Human Neonates

Vitamin A Deficiency Clinical Trial

— NNVAS  

Official title:

A Randomized Controlled Trial in Human Neonates to Determine the Effect of Vitamin A Supplementation on Immune Responses

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01476358
• Other study ID #: RPC389
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 9, 2011
• Last updated: November 12, 2012
• Start date: November 2011

Study information

• Verified date: November 2012
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Gambia: Department of State for Health and Social Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 48 Hours

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Night Blindness
• Vitamin A Deficiency

Intervention

Dietary Supplement:
• 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

Locations

Country	Name	City	State
Gambia	Medical Research Council, The Gambia Unit	Fajara

Sponsors (2)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	World Health Organization

Country where clinical trial is conducted

Gambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of circulating Tregs expressing gut homing receptors in infant participants.		17 week post-supplementation	No
Secondary	Difference in Thymus size in infant participants	Assessed by ultrasonic analysis.	1, 6, 12 and 17 weeks	No
Secondary	Difference in B cell immune responses after routine vaccination in infant participants	Assessed as an increase in B cell numbers and activation status.	6 and 17 weeks	No
Secondary	Improved mucosal barrier function in infant participants	Assessed by quantifying bacterial translocation into the blood.	6 and 17 weeks	No