Zinc Absorption From Zinc Biofortified Rice
Condition: Malnourished Children
MeSH terms: Malnutrition
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      a. To measure the amount of zinc absorbed from ZnBfR compared with the amount absorbed from
      CR and from CR fortified with added zinc, using the triple stable isotope tracer ratio
      technique in young children.

      Methods:

      Investigators will measure the amount of zinc absorbed from ZnBfR compared to that absorbed
      from a conventional Bangladeshi rice (Diet-CR) (control). They will also compare the zinc
      absorption from ZnBfR with that from zinc-fortified conventional rice (Diet-CR+Z). The study
      will be a cross-over, randomized, controlled clinical study. Forty-four children aged 36-59
      mo of either sex will be recruited from the same community as mentioned before, and
      participants will be individually randomized, in equal numbers, to one of the two comparison
      groups, A and B. During an initial one-day acclimatization period, the participants will
      receive the conventional rice-based diet three times a day, to confirm that participants will
      accept the study diets and adhere to the study procedures. On study days 2 and 4, in
      comparison group A, participants will receive either the Diet-ZBfR or Diet-CR based on the
      random assignments, and participants will receive Diet-CR or Diet ZBfR, respectively, on days
      3 and 5 (i.e., the diet not received on days 2 and 4), Likewise, in comparison group B, the
      participants will receive either Diet-ZBfR or Diet-CR+Z on days 2 and 4 based on the random
      assignments, and participants will receive Diet-CR+Z or the Diet-ZBfR, respectively, on days
      3 and 5 (i.e., the diet not received on days 2 and 4). Investigators will use zinc stable
      isotope tracer techniques to measure the fractional absorption of zinc, in which
      tracer:tracee ratios will be measured in spot urine samples following administration of an
      intravenously administered tracer (68Zn) and one of two oral tracers (70Zn, 67Zn) provided
      with test meals over a four-day period.

      Outcome measures/variables:

      Intake of total dietary zinc (TDZ) and phytate for each subject will be calculated during the
      clinical study. Fractional absorption of zinc (FAZ) will be determined from the isotopic
      ratios obtained in urine samples using the following equation, which shows, as an example,
      the calculation that will be used for zinc absorption from the diet traced with 67Zn:

      FAZ = 67Zn tracer:tracee ratio / 68Zn tracer:tracee ratio * (68Zn dose given IV / 67Zn dose
      given orally)

      Total absorbed zinc (TAZ) for each child will be calculated as follows:

      TAZ (mg/d) = TDZ (mg/d) * FAZ
    

Detailed description: 
      It is well documented that zinc supplementation to low-income population results in the
      reduced incidence of childhood diarrhoea and pneumonia, and improves growth of stunted
      children. In Bangladesh, the risk of zinc deficiency is considered to be high and children
      could benefit greatly by improving their zinc intakes on a daily basis. Zinc supplementation
      at a national scale would be a formidable task. There is a need to find an alternative. It
      might be sustainable to improve intake of zinc through fortified staples, e.g. rice with
      increased amounts of zinc; in fact such biofortified rice has been developed through
      conventional breeding, which is designed to contain an amount of zinc that could meet at
      least 40% of the daily requirement.

      In the first round of the previously approved and completed studies, total absorbed zinc
      (TAZ) did not differ when diets containing zinc biofortified rice (ZnBfR) or conventional
      rice (CR) were compared. Thus, the investigators plan to repeat this study using a new
      variety of (ZnBfR)that is expected to have higher zinc content than the variety previously
      studied. Initially, the investigators will also conduct a pilot study in 4 subjects using a
      modified isotope administration protocol such that the oral tracers will be given on two days
      each at half the original dose each day so as to provide a lower proportion of the total
      daily zinc intake as tracer solution.

      Hypotheses:

        1. Young children will have greater total absorbed zinc (TAZ) when participants consume
           mixed diets containing ZnBfR than when participants consume the same diets containing
           CR.

        2. TAZ will not differ in children who receive the ZnBfR-containing diet or the same diet
           containing CR plus sufficient additional zinc to match the zinc content of the ZnBfR
           diet.

      Objectives:

        1. To measure the amount of zinc absorbed from ZnBfR compared with the amount absorbed from
           CR and from CR fortified with added zinc, using the triple stable isotope tracer ratio
           technique in young children.

        2. To assess the intestinal function of the children, using a sugar permeability test
           (lactulose:mannitol test).

        3. (Pilot study) To verify that the modified tracer dose will provide adequate signal for
           assessing zinc absorption.

      Methods:

      To assess the potentials for biofortified rice in providing a good, bioavailable source of
      additional zinc, the investigators propose to measure zinc absorption from rice-based meals
      among Bangladeshi preschool children. The investigators will measure the amount of zinc
      absorbed from ZnBfR compared to that absorbed from a conventional Bangladeshi rice (Diet-CR)
      (control). The investigators will also compare the zinc absorption from biofortified rice
      with that from zinc-fortified conventional rice (Diet-CR+Z). The study will be a cross-over,
      randomized, controlled clinical study. Initially, a pilot study will be conducted with a
      modified dose of zinc stable isotope among 4 children aged 36-59 months of either sex from a
      peri-urban community in Dhaka. Later on, 44 children aged 36-59 months of either sex will be
      recruited from the same community as mentioned before, and participants will be individually
      randomized, in equal numbers, to one of the two comparison groups, A and B. During an initial
      one-day acclimatization period, the study children will receive the conventional rice based
      diet three times a day, to confirm that participants will accept the study diets and adhere
      to the study procedures. On study days 2 and 4, in comparison group A, the study subjects
      will receive either the Diet-ZBfR or Diet-CR based on the random assignments, and
      participants will receive Diet-CR or Diet ZBfR, respectively, on days 3 and 5 (i.e., the diet
      not received on days 2 and 4), Likewise, in comparison group B, the study subjects will
      receive either Diet-ZBfR or Diet-CR+Z on days 2 and 4 based on the random assignments, and
      participants will receive Diet-CR+Z or the Diet-ZBfR, respectively, on days 3 and 5 (i.e.,
      the diet not received on days 2 and 4). The investigators will use zinc stable isotope tracer
      techniques to measure the fractional absorption of zinc, in which tracer : tracee ratios will
      be measured in spot urine samples following administration of an intravenously administered
      tracer (68Zn) and one of two oral tracers (70Zn, 67Zn) provided with test meals over a
      four-day period.

      Outcome measures/variables:

      Intake of total dietary zinc (TDZ) and phytate for each subject will be calculated during the
      clinical study. Fractional absorption of zinc (FAZ) will be determined from the isotopic
      ratios obtained in urine samples using the following equation, which shows, as an example,
      the calculation that will be used for zinc absorption from the diet traced with 67Zn:

      FAZ = 67Zn tracer:tracee ratio / 68Zn tracer:tracee ratio * (68Zn dose given IV / 67Zn dose
      given orally)

      Total absorbed zinc (TAZ) for each child will be calculated as follows:

      TAZ (mg/d) = TDZ (mg/d) * FAZ
    

Intervention name(s): Diet-ZnBfR; Diet- CR; Diet-ZnBfR; CR + Zn
Intervention type(s): Other; Other; Other; Other
Intervention description(s): zinc biofortified rice-based diet; conventional rice-based diet; zinc biofortified rice-based diet; conventional rice-based diet plus zinc fortificant (Diet-CR+Z).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science