Influenza Virus Vaccine Plus Vitamin A and D Supplements for Prevention of Respiratory Virus Infections in Children
Condition: Healthy Participants
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      Children are particularly vulnerable to respiratory virus infections, especially influenza.
      Vitamin A & D deficiencies are associated with vulnerability to infectious diseases of the
      respiratory tract. The central hypothesis of this protocol is that vitamin supplements will
      enhance antibody responses toward the flu vaccine in children. Children, 2-8 years old, will
      be randomized to receive influenza virus vaccine with a vitamin A+D supplement or influenza
      virus vaccine with placebo. Children will be tested for vitamin levels and immune responses
      before and after influenza virus vaccinations to determine if vitamin supplementation
      improves the influenza virus vaccine-induced immune response.

      PRIMARY OBJECTIVE:

        -  To assess the vaccine-induced and total antibody (including IgG and IgA) response after
           influenza virus vaccine administration and IgA/IgG plus IgA/IgM ratios at 28 and 56 days
           in sera

      SECONDARY OBJECTIVE:

        -  To assess the neutralizing response toward influenza virus vaccine in the sera.
    

Detailed description: 
      Participants will be randomized to receive either an influenza virus vaccine plus Vitamins A
      & D or an influenza virus vaccine plus placebo. They will be stratified based on retinol
      binding protein (RBP) levels at screening, using a cut-off indicative of Vitamin A
      insufficiency (≤22,000 ng/ml). Co-enrolled sibling participants will be first stratified by
      RBP levels, then siblings within the same stratum will be equally assigned to different arms
      to provide greater assurance of balanced treatment assignment. Children will be tested for
      vitamin levels and immune responses before and after influenza virus vaccinations to
      determine if vitamin supplementation improves the influenza virus vaccine-induced antibody
      immune response.

      All participants will receive two doses of an influenza virus vaccination administered at
      least 28 days apart. Vitamin levels and antibody responses toward the vaccine will be
      measured on day 0 (baseline levels obtained where day 0 equals the first influenza virus
      vaccination administration), day 28, and day 56. Placebo or Vitamins A + D (at the levels of
      20,000 IU and 2,000 IU, respectively) will be administered orally on the days of vaccination.

      Blood serum samples will be collected from participants on Day 0, prior to receiving
      influenza virus vaccine on Day 28, and during their Day 56 follow-up visit.

      Parents will be asked to fill out diary cards to indicate food intake for children during the
      study period along with an optional food frequency questionnaire given on day 56. Specific
      measurements on days 28, and 56 will include analyses of vaccine-specific and total IgA, IgG,
      and IgA/IgG plus IgA/IgM ratios in sera. Functional activities of antibodies toward influenza
      vaccine will also be measured.
    

Intervention name(s): Influenza virus vaccine; Vitamins A and D; Placebo
Intervention type(s): Biological; Dietary Supplement; Other
Intervention description(s): Children will have the first influenza virus vaccine dose (dose 1) administered on day 0 of the trial, and the second dose (dose 2) administered 28 days later.; The chewable gummy contains either Vitamin A (20,000 International Units) and Vitamin D3 (2,000 International Units), which should be fully chewed under supervision of study staff with documentation in the participant's research record and eMAR (electronic medical administration record). The chewable gummy should be administered prior to receiving influenza virus vaccination.; The chewable gummy matched placebo will be formulated with gelatin base and tangerine oil and match the Vitamin A and D in shape, taste, texture, and appearance. Gummies should be fully chewed under supervision of study staff with documentation in the participant's research record and eMAR (electronic medical administration record). The chewable gummy should be administered prior to receiving influenza virus vaccination.
Other intervention name(s): Fluzone®; Nutritional Supplement; Look-alike Medication; Matched Placebo
Intervention MeSH terms: Vitamin D; Vitamin A
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Children; Vitamin Supplements; Influenza virus vaccine