Novel Isotope Dilution Technique to Assess Vitamin A Status
Condition: Healthy Infants; Infants With an Inflammatory Condition
Study type: Interventional

Summary: 
      Background:

      There is no reliable method for vitamin A (VA) assessment for infants and young children.
      Serum VA concentration is not an authenticate indicator of VA status, while existing
      deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks
      and not applicable for infants and children. The investigator's research group recently
      developed a new simplified equation to measure VA pool size in 4-5 days, correlated with
      compartmental model-predicted value and estimate VA pool size in adults with high precision.
      In this study, we validate the method in healthy infants and infants with an inflammatory
      condition.

      Hypothesis:

      Whole-body VA status in infant and children can be estimated without accounting for the
      fractional catabolic rate in the context of an inflammatory condition

      Specific Objectives:

      In this study, the investigators propose to determine the early time point equation for
      assessing VA pool size in infants with or without inflammatory condition using model-based
      compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma
      over time.

      Methods:

      A total of 183 infants (9-18 mo of age) will participate in this study in the following two
      phases of the "Super Kid study" that ensure no more than 2 venous blood samples from each
      infant, even though multiple time points (at least 4 subjects / time-point) over a 28-day
      study period will be available for mathematical modeling. In this study, investigators will
      use two different stable isotopic vitamin A e.g., 13C10-retinyl acetate and 13C4-retinyl
      acetate. 400 μg of these isotopes, dissolved in 0.5 mL of sunflower oil, will be provided
      directly into the infant's mouth by using a direct replacement pipette. Mothers will be asked
      to breastfeed their infant after oral dosing to enhance absorption of the labeled vitamin A.
      Specific activity of 13C10- and 13C4- retinyl acetate in the blood samples will be measured
      by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Dietary and morbidity
      questionnaires will be used. Investigators will also use PENTA vaccines as a means to induce
      controlled inflammation (closely mimic to natural infection). PENTA is a combination of five
      different vaccine antigens (Hepatitis B (HBV)/ Haemophilus influenza type b (Hib) /
      Tetanus-Diphtheria-whole cell Pertussis (TDwP)). This vaccination is beneficial to the
      infants since the World Health Organization recommends a booster vaccination dose. At the end
      of the study, PENTA vaccines will also be provided to the study infants in the "no-vaccine"
      group.

      (A) 115 infants will be enrolled randomly into 16 groups of them 40 infants will be in the
      first group, while other infants will be assigned in the other 15 groups (n=5/group). On day
      0 (at 0h), all infants (n=115) will receive an oral dose of 13C10-retinyl acetate. Blood
      samples (5 mL) will be taken from 6h to 16th day of dosing at 9 different time-points. On day
      16 (at 0h), randomly selected 50% infants (n=20) in the first group, as well as 30 infants in
      the other 6 groups, will receive PENTA vaccines, while the other 50% infants (n=20) in the
      first Group, as well as 45 infants in the other 9 groups, will receive no vaccines. 24 hours
      after vaccination (On day 17) a finger-prick blood sample will be obtained from the infants
      in the vaccinated group to measure CRP (QuikRead go, Orion, Finland). Infants who do not
      develop inflammation (CRP> 5mg/L) after PENTA vaccination will be excluded from the study. On
      day 17 (at 0h), all infants (n=115) will receive another oral dose of 13C4-retinyl acetate.
      Blood samples (5mL) will be collected from day 16 to day 28 at 11 different time-points for
      each of the vaccinated and non-vaccinated infants. This study will also assess the absorption
      of isotopic retinol by determining in total excreted stool up to 72 h post isotope dosing in
      a subsample of infants

      (B) 68 infants will be enrolled in this phase. Of them, 28 infants will be assigned randomly
      into 7 groups (n=4/group). They will receive PENTA vaccines on day -1, and the next day (day
      0) they will receive an oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be
      collected from day 1 to day 28 at 8 different time points. In a separate design, 40 infants
      will receive an oral dose of 13C10-retinyl acetate on day 0 and blood samples (5mL) will be
      collected on day 4. On day 7 they all will receive another oral dose of 13C4-retinyl acetate
      (400 μg, dissolved in 0.5 mL of sunflower oil). On day 10, infants will receive PENTA
      vaccines (n=30) or no vaccine (n=10) and 1-day after vaccination, blood samples (5 mL) will
      be obtained from infants who develop inflammation (CRP> 5mg/L) in the vaccine group and also
      from infants in the control group (day 11).

      Outcome measures:

      The early time point equation for assessing VA pool size in a group of infants with or
      without inflammation
    


Intervention name(s): Vaccine
Intervention type(s): Biological
Intervention description(s): Pentavalent vaccine. It is a combination of five different antigens (Hepatitis B (HBV)/ Haemophilus influenzae type b (HiB) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)).
Other intervention name(s): PENTA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: vitamin A; vitamin A isotope; Inflammation