Safety and Effectiveness of Iron Hydroxide Adipate Tartrate (IHAT) in Iron Deficient Premenopausal Women

This is a double blind, randomised, placebo-controlled trial to evaluate orally-dosed Iron Hydroxide Adipate Tartrate (IHAT) at 2 different dose levels compared to placebo for increasing serum ferritin levels in iron deficient, but otherwise healthy premenopausal women over 12 weeks.

IHAT is a novel bioavailable source of iron. It is a tartrate-modified, nanoparticulate ferric oxo-hydroxide with similar functional properties and small primary particle size to the iron form found in the ferritin core (ferrihydrite).

In this trial, subjects will be randomly assigned to receive either (1) IHAT once a day, (2) IHAT twice a day or (3) a placebo daily for 12 weeks. The primary endpoint is the correction of iron deficiency at week 12. Secondary endpoints include iron status, iron deficiency symptoms and gastrointestinal symptoms over the course of the 12 weeks.

• Low Dose IHAT (Drug): Once daily dose of 1 IHAT capsule (100mg IHAT per capsule) and once daily dose of 1 placebo capsule (carob flour)
• High Dose IHAT (Drug): Twice daily dose of 1 IHAT capsule (100mg IHAT per capsule)
• Carob Flour (Drug): Twice daily dose of 1 placebo capsule (carob flour)

Primary outcomes

• Percentage of women recovering from iron deficiency at week 12 [week 12]: Percentage of women recovering from iron deficiency at week 12, defined as serum ferritin levels of 30 - 150 ug/L

Secondary outcomes

• Time to reach normalisation of ferritin levels [Baseline, week 6 and week 12]: Time to reach normalisation of ferritin levels via blood test results
• Change in iron status [Baseline, week 6 and week 12]: Iron status assessed by serum ferritin in ug/L, haemoglobin in g/dL, serum iron in uM and transferrin saturation, defined as serum iron divided by total iron binding capacity and expressed as a percentage
• Change in fatigue [Baseline, week 6 and week 12]: Change in fatigue via Fatigue Severity Scale
• Incidence and prevalence of gastrointestinal side effects [Baseline, week 1-6 and week 12]: Incidence and prevalence of gastrointestinal side effects via gastrointestinal symptom questionnaire
• Iron deficiency symptoms [Baseline, week 6 and week 12]: Iron deficiency symptoms via 36-Item Short Form Survey Instrument (SF-36)

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Generally healthy iron deficient premenopausal women, with iron deficiency defined as serum ferritin < 30 ug/L and generally healthy as C-reactive protein < 3mg/L (1)
* Able to provide informed consent
* Agree not to participate in another clinical trial while enrolled in this trial
* Agree not to give blood donations during the study
* Agree not to change current diet (subjects adhering to a vegetarian or vegan diet are allowed to participate) and/or exercise frequency or intensity

Exclusion Criteria:

* Anaemia (as determined from the haematocrit and haemoglobin measures) (2)
* Subjects regularly taking iron specific supplements during or 2 months prior to study commencement (the use of other mineral/vitamin/herbal preparations is allowed but should be recorded) (3)
* Any uncontrolled serious illness (4)
* Previously told they have an iron absorption problem
* Receiving/prescribed coumadin (Warfarin), heparin, dalteparin, enoxaparin or other anticoagulation therapy
* active smokers, nicotine use, alcohol (5) or drug (prescription or illegal substances) abuse
* chronic gastrointestinal disorders
* Pregnant/lactating women or women trying to conceive
* Diagnosed depression or mental disorder that is uncontrolled
* Eating disorders
* BMI > 35 kg/m2
* Allergic to any of the ingredients in active or placebo formula
* Any condition which in the opinion of the investigator makes the participant unsuitable for inclusion
* Participants who have participated in any other clinical trial during past 1 month

Footnotes:

1. A blood test is required prior to enrolment into the study to receive trial product. Participants will be required to attend a local pathology collection centre and have serum ferritin and CRP within the required limits to be considered enrolled in the study and be provided with trial product.
2. Anyone considered to be anaemic will be excluded and directed to their GP. In women, anaemia is defined as any of the following: Haemoglobin < 115 g/L, Haematocrit < 35%.
3. Potential participants that are taking supplements that would result in their exclusion must wait an 8-week washout period prior to commencing the study.
4. An uncontrolled illness is any illness that is currently not being treated with a stable dose of medication or is fluctuating in severity. A serious illness is a condition that carries a risk of mortality, negatively impacts quality of life and daily function and/or is burdensome in symptoms and/ or treatments.
5. Chronic past and/or current alcohol use (>14 alcohol drinks/week).

• Maria Cristina Comelli, PhD, Study director, Nemysis Ltd