Stable Iron Isotope Method in HIV+ and HIV- Children
Condition: Iron-deficiency
MeSH terms: Iron Deficiencies
Study type: Interventional

Summary: 
      The objective of this study is to compare HIV infected children to uninfected children
      regarding 1) quantifying iron absorption from iron fortified maize porridge, lipid-based food
      supplements and oral iron supplements, and 2) quantifying the daily iron requirement.
    

Detailed description: 
      In Sub-Saharan Africa, HIV is a major cause of morbidity and mortality in children. Anemia
      frequently complicates pediatric HIV infection and predicts disease progression and
      mortality. Iron requirements and the specific contribution of iron deficiency (ID) to anemia
      in pediatric HIV infection remains uncertain. The fundamental barrier to understanding iron
      nutrition in HIV infection is that sub-clinical inflammation in individuals with HIV
      infection confounds the usual bio-markers used to assess iron status and response to iron
      interventions. A novel iron stable isotope technique developed by ETH Zurich, Switzerland, is
      a promising new tool for better understanding of iron metabolism in HIV infection. In
      contrast to existing conventional bio-markers of iron status, a method based on isotopic
      dilution of whole body iron labeled with stable, non-radioactive isotopes of iron (58Fe,
      57Fe) could directly quantify iron requirements, as well as iron absorption from
      interventions, completely free of bias and confounding by inflammation. This method could
      offer, for the first time, a long-term quantitative measure of iron balance and absorption
      from iron interventions and provide reliable data on which to base nutrition recommendations
      for HIV infection.

      The objective is to compare HIV infected children to uninfected children: 1) Quantify iron
      absorption from iron fortified maize porridge, lipid-based food supplements and oral iron
      supplements; 2) Quantify the daily iron requirement.

      The study participants will be recruited from the South African Stellenbosch
      University/Tygerberg Children's Hospital long-term antiretroviral therapy (ART) cohort of
      perinatally HIV infected children and uninfected controls from the same communities, matched
      by age and gender. As a secondary outcome, we want to investigate the effect of iron
      supplementation on the gut microbiome.

      In study 1, using a randomized cross-over design and stable isotope labeled single meal/doses
      the investigators will: a) quantify the impairment of dietary iron absorption in HIV
      infected, iron deficient children compared to HIV uninfected, iron deficient controls using a
      labeled iron fortified maize meal, a lipid-based nutritional supplement (LNS) and an oral
      iron supplement; and b) administer sufficient iron isotope label (57Fe) to allow
      equilibration and follow up of isotopic composition in the blood for two years (isotope
      dilution technique). At the end of Study 1, all iron deficient children will be iron replete
      prior to entering Study 2. In study 1, in parallel, a group of HIV infected and uninfected,
      iron sufficient children will be given orally 12 mg 57Fe as ferrous sulfate (FeSO4).

      In study 2, the investigators will apply the principle of long-term isotope dilution to
      quantify the daily iron requirement in both the HIV infected and uninfected children, and the
      difference in iron requirements.

      The overall goal is to provide optimized recommendations on dietary iron requirements and
      iron treatment regimens in HIV infected children, in order to reduce ID and anemia, improve
      their health and well-being, their long-term prognosis and quality of life.
    

Intervention name(s): FeFum fortified maize test meal; FeSO4 fortified LNS; FeSO4 supplement; FeSO4 fortified fruit juice
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Maize porridge extrinsically labeled with 2 mg ferrous fumarate (58FeFum); only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L); cereal staple foods, like maize, depending on milling, may be high in phytic acid, a potent iron absorption inhibitor; self-made Lipid-based nutritional supplement (LNS) extrinsically fortified and labeled with 6 mg ferrous sulfate (57FeSO4); only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L); LNS may be a better food matrix for iron supplementation compared to maize-based porridge; contains canola oil, peanut paste, milk powder, sugar, maltodextrin and palm stearin; 170 mg iron tablets as FeSO4 (containing 55 mg of elemental iron) with 6 mg extrinsically labeled 57Fe; will be given together with a glass of water; only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L);; Fruit juice labeled with 12 mg 57Fe as FeSO4; in the group for iron sufficient children
Intervention MeSH terms: Fesoterodine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment