Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

IHAT Absorption Kinetics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02498886
Recruitment Status : Completed
First Posted : July 15, 2015
Last Update Posted : February 6, 2017
Sponsor:
Information provided by (Responsible Party):
dora pereira, Medical Research Council

Brief 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.


Condition or disease Intervention/treatment Phase
Iron-deficiency Anemia Dietary Supplement: IHAT Dietary Supplement: Ferrous sulphate Early Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: An Exploratory Study to Determine Bioavailability and Transferrin Saturation Following a Single Dose of a Novel Iron Supplement (IHAT) in Gambian Women.
Study Start Date : August 2015
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron

Arm Intervention/treatment
Experimental: Iron deficient anaemic: IDA

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.

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.

Experimental: Iron sufficient: non-IDA

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.

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.

Experimental: Iron deficient anaemic (IDA): IHAT new manufacture

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.

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.




Primary Outcome Measures :
  1. Relative bioavailability value of IHAT versus ferrous sulphate [ Time Frame: 14 days ]
    This will be determined from the red blood cell incorporation of isotope-labelled iron 14 days following a single oral dose.


Secondary Outcome Measures :
  1. Serum iron [ Time Frame: 6 hours ]
    Serum iron will be determined at 0, 2, 4, 6 hours following a single dose of each iron compounds (i.e. on days 1 and 14).

  2. Transferrin saturation [ Time Frame: 6 hours ]
    Tsat will be determined at 0, 2, 4, 6 hours following a single dose of each iron compounds (i.e. on days 1 and 14).

  3. Pathogen Growth [ Time Frame: 6 hours ]
    Pathogen growth will be determined using ex vivo assays in serum collected from each subject at 0, 2, 4 and 6 hours following a single dose of each compound (days 1 and 14).

  4. Plasma iron [ Time Frame: 6 hours ]
    Plasma 58Fe and 57Fe will be determined at 0, 2, 4, 6 hours (on days 1 and 14).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02498886


Locations
Layout table for location information
Gambia
MRC Unit The Gambia
Keneba, West Kiang, Gambia
Sponsors and Collaborators
Medical Research Council
Investigators
Layout table for investigator information
Principal Investigator: Dora I Pereira, PhD Medical Research Council

Publications:
Layout table for additonal information
Responsible Party: dora pereira, Senior Investigator Scientist, Medical Research Council
ClinicalTrials.gov Identifier: NCT02498886     History of Changes
Other Study ID Numbers: 1422
First Posted: July 15, 2015    Key Record Dates
Last Update Posted: February 6, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Iron-Deficiency
Anemia, Hypochromic
Anemia
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Iron
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs