IHAT Absorption Kinetics
Condition: Iron-deficiency Anemia
MeSH terms: Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional
Phase: Early Phase 1

Summary: 
      At MRC Human Nutrition Research, the investigators have developed an engineered analogue of
      the ferritin-core for safe and effective iron supplementation. Iron hydroxide adipate
      tartrate (IHAT) is a tartrate-modified, nano-disperse Fe(III) oxo-hydroxide, formed in an
      adipate buffer, with similar functional properties and small primary particle size (~2 nm) as
      the iron found in the ferritin core; it better mimics iron absorption from food than the
      non-physiological bolus doses of ferrous sulphate currently used.

      This exploratory study will test the hypothesis that IHAT has equivalent bioavailability to
      ferrous sulphate but produces a less harmful post-ingestion rise in transferrin saturation.
      The design is a 3-arm (IDA, non-IDA and IDA-IHAT new manufacture), crossover, randomised,
      single-dose study.

      Primary endpoint:

      Relative bioavailability value of IHAT versus ferrous sulphate. This will be determined from
      the red blood cell incorporation of isotope-labelled iron 14 days following a single oral
      dose.

      Secondary endpoints:

      Serum iron at 0, 2, 4, 6 hours following a single dose of each iron compound. Transferrin
      saturation at 0, 2, 4, 6 hours following a single dose of each iron compound.

      Plasma 58Fe and 57Fe at 0, 2, 4, 6 hours. Pathogen growth using ex vivo assays in serum
      collected from each subject at 0, 2, 4 and 6 hours following a single dose.
    

Detailed description: 
      The study's main hypothesis is that IHAT will be bioavailable in pre-menopausal anaemic
      Gambian women and will lead to a lower serum iron and transferrin saturation increase than an
      equivalent dose of ferrous sulphate. Furthermore, the investigators hypothesize that IHAT
      will produce a less harmful post-ingestion rise in transferrin saturation, i.e. the serum
      collected from subjects following a single dose of IHAT will promote less pathogen growth in
      ex vivo assays than that collected following an equivalent dose of ferrous sulphate. Finally,
      based on previous animal data [5], the investigators hypothesize that IHAT absorption will be
      significantly higher in anaemic women compared to non-anaemic women, and that this will not
      be the case with ferrous sulphate.

      This study is a cross-over, single-dose comparison against ferrous sulphate (standard of
      care) in anaemic and non-anaemic women. The iron single dosage for both compounds will be
      60mg elemental iron equivalent and each compound will be labelled with a stable iron isotope.
      Outcomes will be: red blood cell incorporation of labelled iron, serum iron, transferrin
      saturation and pathogen growth in ex vivo serum assays.

      Primary objective:

      To determine iron bioavailability (i.e. red blood cell incorporation) from a single dose of
      IHAT versus ferrous sulphate in pre-menopausal Gambian women.

      Secondary objective:

      To determine serum iron absorption following a single dose of IHAT versus ferrous sulphate in
      pre-menopausal Gambian women.

      To evaluate if a single-dose of IHAT produces a less harmful post-ingestion rise in
      transferrin saturation and serum iron than ferrous sulphate.

      Each compound is labelled with a stable isotope of Fe so that its absorption can be
      determined from the red blood cell incorporation of the stable isotope 14 days after the
      single dose. This study is effectively a Phase 0 study (pharmacokinetics) with small numbers
      and because iron absorption varies from individual to individual, depending on their body
      iron needs and gastrointestinal digestion issues, it is more accurate to use each study
      subject as her own control. Therefore, each subject will ingest IHAT on one study day and the
      active treatment comparator on a separate day. The 2 study visits need to be 14 days apart to
      allow for red blood cell incorporation of the stable iron isotopes used to label the iron
      materials. This method is the gold standard to determine relative bioavailability values
      (RBV) of novel iron compounds (i.e. in relation to ferrous sulphate absorption) and allows an
      accurate determination of RBV of IHAT that otherwise would not be possible if we used a
      parallel study design with small numbers.
    

Intervention name(s): IHAT; Ferrous sulphate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Iron hydroxide adipate tartrate (IHAT): Single dose capsule containing IHAT equivalent to 60mg iron with 2 mg isotopically enriched with 58Fe.; Ferrous sulphate: Single dose capsule containing ferrous sulphate heptahydrate equivalent to 60 mg iron with 10 mg isotopically enriched with 57Fe.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science