NCT02498886

IHAT Absorption Kinetics

An Exploratory Study to Determine Bioavailability and Transferrin Saturation Following a Single Dose of a Novel Iron Supplement (IHAT) in Gambian Women.

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Medical Research Council · Other Government
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Iron-deficiency Anemia

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	IHAT	Iron hydroxide adipate tartrate (IHAT): Single dose capsule containing IHAT equivalent to 60mg iron with 2 mg isotopically enriched with 58Fe.
DIETARY_SUPPLEMENT	Ferrous sulphate	Ferrous sulphate: Single dose capsule containing ferrous sulphate heptahydrate equivalent to 60 mg iron with 10 mg isotopically enriched with 57Fe.

Timeline

• Start date: 2015-08-01
• Primary completion: 2016-03-01
• Completion: 2016-03-01
• First posted: 2015-07-15
• Last updated: 2017-02-06

Locations

1 site across 1 country: The Gambia