IHAT Absorption Kinetics

United Kingdom Research and Innovation (UKRI)

Status and phase: Completed; Early Phase 1

Conditions: Iron-deficiency Anemia

Treatments: Dietary Supplement: Ferrous sulphate; Dietary Supplement: IHAT

Study type: Interventional

Funder types: Other

Identifiers

NCT02498886

1422

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Pre-menopausal women apparently healthy (as judged by a study nurse at the screening day) with normal CRP (measured at screening).
• Non-pregnant (will be tested with a rapid pregnancy test) and non-lactating women.
• IDA arm: 9≤Hb≤11 g/dL and ferritin≤ 15 ng/ml
• Non-IDA arm: Hb>11 g/dL and ferritin> 15 ng/ml.

Exclusion criteria

• Malaria and other infections
• Severe anaemia (Hb<9 g/dL)
• CRP> 5 mg/L
• Chronic disease
• Currently participating in other iron intervention studies.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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34 participants in 3 patient groups

Iron deficient anaemic: IDA

Experimental group

Description:

Iron deficient anaemic women. Interventions: two iron supplements will be used: IHAT- iron hydroxide adipate tartrate: an analogue of natural food iron. Ferrous sulphate- the gold standard for iron supplementation. For both the iron single-dose will be 60mg elemental iron equivalent. Each compound will be labelled with a stable isotope of iron: IHAT with 2 mg 58Fe and ferrous sulphate with 10 mg 57Fe. 1 capsule of each compound will be ingested with a full glass of water in two separate occasions, 14 days apart.

Treatment:

Dietary Supplement: Ferrous sulphate

Dietary Supplement: IHAT

Iron sufficient: non-IDA

Experimental group

Description:

Women that are not anaemic or iron deficient. Interventions: two iron supplements will be used: IHAT- iron hydroxide adipate tartrate: an analogue of natural food iron. Ferrous sulphate- the gold standard for iron supplementation. For both the iron single-dose will be 60mg elemental iron equivalent. Each compound will be labelled with a stable isotope of iron: IHAT with 2 mg 58Fe and ferrous sulphate with 10 mg 57Fe. 1 capsule of each compound will be ingested with a full glass of water in two separate occasions, 14 days apart.

Treatment:

Dietary Supplement: Ferrous sulphate

Dietary Supplement: IHAT

Iron deficient anaemic (IDA): IHAT new manufacture

Experimental group

Description:

Iron deficient anaemic women. Interventions: two iron supplements will be used: IHAT new manufacture- iron hydroxide adipate tartrate: an analogue of natural food iron. Ferrous sulphate- the gold standard for iron supplementation. For both the iron single-dose will be 60mg elemental iron equivalent. Each compound will be labelled with a stable isotope of iron: IHAT with 2 mg 58Fe and ferrous sulphate with 10 mg 57Fe. 1 capsule of each compound will be ingested with a full glass of water in two separate occasions, 14 days apart.

Treatment:

Dietary Supplement: Ferrous sulphate

Dietary Supplement: IHAT