Iron Deficiency and/or Anemia Clinical Trial
Official title:
Comparison of Iron Absorption From Extruded FePP-fortified Rice Containing Different Zinc Compounds, Citric Acid/Trisodium Citrate and Sodium EDTA
Rice can only be fortified with ferric pyrophosphate (FePP), which is of low bioavailability
in human subjects. Compounds such as citric acid/trisodium citrate (CA/TSC) or sodium
ethylene-diamine tetraacetic-acid (EDTA) could serve as absorption enhancers. Recent
findings from single meal studies indicate CA/TSC to have an enhancing effect on iron
absorption from FePP-fortified rice. In contrast, ZnO has been suggested to have detrimental
effects. Furthermore, in vitro findings suggest an increased iron solubility from iron and
EDTA-co-fortified rice - but the bioavailability in humans remains to be investigated. These
effects should thus be investigated in 'real-life' conditions, when fortified rice is
implemented in a complete diet administered throughout several days in a target population
for a rice fortification program.
Objective: To assess iron absorption from the diet from different iron fortified rice
formulations in iron deficient anaemic children.
The investigators aim to conduct an iron absorption study in 30 Ghanaian school-age children
investigating different fortification approaches in a multiple meal randomized, cross over
study.
Iron of differing molecular weights (54Fe, 56Fe, 57Fe, 58Fe) and other nutrients and
additives will be extruded into rice kernels, these kernels will be blended with regular
unfortified rice and administered to the study participants.
Recruitment of study participants will be through a local investigator in close
collaboration with the Ghanaian school authorities. Before starting the study, 6 children
will be asked to participate in a pilot testing, where they will be administered 2 portions
of rice (50 g dry weight) with a vegetable sauce with a four hours delay in between the
meals. This is to allow the investigators to define, the optimal portion size, that will be
used throughout the study. For their participation, the children will receive a small
symbolic gift. The investigators envisage screening approximately 60 children living in
Tamale and surrounding rural areas at least one week before study start. Recruitment of
participants will be done until reaching a number of 30 eligible participants. Participant's
caretakers will be explained the study procedures and need to sign a consent form before the
participant is exposed to any study procedure. Participants at screening will be assigned a
unique study identification (running number and participant's initials), which they will
keep if included in the study. All data will be kept confidential. The medical history,
dietary intake data and data concerning socioeconomic status will be assessed using
questionnaires, body temperature, height and weight will be measured and z-scores (weight
for age) will be calculated. A blood sample will be collected from each participant for the
initial determination of iron status, detection of parasitic infections (including
measurements of hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR),
Zinc protoporphyrin to heme ratio (ZPP), C-reactive protein (CRP), Alpha acid glycoprotein,
and malaria parasitemia. All screened participants will receive an appropriate dose of an
anthelmintic free of charge, unless they had received an according treatment within the last
two months. Based on the information obtained from screening, in-/ exclusion criteria will
be checked and participant's eligibility will be judged accordingly. Thirty iron deficient
and/or anemic children (hereafter called participants) will be included in the absorption
study. For the initial determination of the iron status and infection detection, the
children will receive a symbolic gift from the investigators. There will be no monetary
compensation for participation; however, the children or their caregivers will receive a
symbolic gift for completion of the study. Potential transport costs for the children and
their caregivers will be covered by the project.
The whole study duration will be eleven weeks (excluding screening and pilot testing).
Participants will donate one blood sample at screening and two blood samples during the
remaining study period. Between Monday and Friday, the participants will receive two meals
per day, one in the morning (first meal) and one at noon (second meal). One type of test
meal will always be administered throughout five consecutive days. In total each participant
will receive 60 rice meals each meal consisting of approximately 50 g regular unfortified
rice, 0.5 g extruded fortified rice, 30 g sauce and 250 ml water. The definite rice amount
administered will be decided upon after a pilot investigation. The order of the test meals
given in each week will be partially randomized. Thus, if test meals A, B or C will be given
throughout 1 week between weeks 1 and 3, test meals D, E and R will be given between weeks 6
and 8. Meals containing iron with the same molecular weight (58 Fe, 57Fe and 54Fe) have to
be administered at least 16 days apart from each other, which is the only restriction for
randomization. The participants are not allowed to eat after 8 PM and to drink after 12 AM
on the day before each study visit, between the meals and for three hours after they
finished their second meal, unless they are given snacks by the investigators and are
explicitly allowed to eat those. Each meal administration will take approximately 25
minutes. This procedure will be followed for six weeks, with a two weeks break between weeks
3 and 6 (no dietary restrictions within the break-period).
The test meals will be based on 50 g regular unfortified rice and 0.5 g extruded fortified
rice (dry weight). The meals will be administered with one of two traditional sauces, with a
low (sauce A) or moderate (sauce B) phytic acid (PA) content. Sauce A will be based on
tomatoes and onions, sauce B will be based on cowpeas. The rice meals will be prepared
individually for each subject, the sauce will be prepared in bulk before the study start.
All meals will be served with 250 ml water. The test meals are designed to match ~2/3 of the
average dietary requirements in that age-group. In case the rice meals do not provide enough
energy (~700 - 900 kcal), the investigators will administer a standardized snack to be
consumed during the fasting periods.
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Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research