Comparison of Iron Absorption From Extruded FePP-fortified Rice Containing Zinc, Citric Acid/Trisodium Citrate and EDTA
Condition: Iron Deficiency and/or Anemia
MeSH terms: Iron Deficiencies
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ferric Pyrophosphate and Zinc Oxide; Ferric Pyrophosphate and Zinc Sulphate; Ferric Pyrophosphate, ZnO, Citric Acid and Trisodium Citrate; Ferric Pyrophosphate, ZnSO4, CA/TSC; Ferric Pyrophosphate, ZnO, CA, EDTA; Ferrous Sulphate
Intervention type(s): Other; Other; Other; Other; Other; Other
Intervention description(s): Extruded rice fortified with Ferric Pyrophosphate, Zinc Oxide (ZnO) and micronutrients; Extruded rice fortified with Ferric Pyrophosphate, Zinc Sulphate (ZnSO4) and micronutrients; Extruded rice fortified with Ferric Pyrophosphate, Zinc Oxide (ZnO), Citric Acid (CA) and Trisodium Citrate (TSC) and micronutrients; Extruded rice fortified with Ferric Pyrophosphate, ZnSO4, CA/TSC and micronutrients; Extruded rice fortified with Ferric Pyrophosphate, ZnO, CA, EDTA and micronutrients; Extruded rice fortified with micronutrients, Ferrous Sulphate solution will be added at consumption
Intervention MeSH terms: Zinc; Iron; Zinc Sulfate; Zinc Oxide; Citric Acid; Sodium Citrate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research