Clinical trial NCT02050932: The Optimization of Iron Bioavailability of Supplements Using Hepcidin Levels in Humans
Official title: The Optimization of Iron Bioavailability of Supplements Using Hepcidin Levels in Humans: Effect of the Time of Administration and Consecutive Day Administration of Commonly Used Dosages
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron Deficiency
Keywords: hepcidin
iron bioavailability
iron supplementation
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
First posted: 2014-01-31
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Background: Oral iron supplementation (OIS) is a widely-used strategy to treat iron deficiency anemia. However, absorption of OIS is often low and response is variable. To overcome this, large doses are given but this may reduce compliance due to gastric irritation. Thus, OIS doses should be low, while maximizing absorption. The prevailing serum hepcidin concentration (SHep) is the major determinant of iron absorption and erythrocyte iron utilization. Based on limited data in humans, SHep can be increased by a single OIS dose but the duration of the increase is uncertain: In a recent study conducted in our laboratory it has been found to last approx. 24 h. Also, there are few data on how the increase in SHep determines the absorption of further doses of oral iron. Is there a threshold SHep at which subsequent iron absorption is sharply reduced? Better understanding of this relationship would be valuable to design more effective and safer OIS regimens.

Objectives: 1) Determine whether two consecutive dosages of 60 mg Fe differently affect hepcidin response and iron bioavailability (Study 1) 2) Compare the bioavailability of iron supplement dosages given at different times of the day (Study 2).

Methods/Subjects: Healthy female subjects will be screened for low iron status. Anemic subjects will be excluded from the study. Thirty two subjects will be included with serum ferritin \<20 µg/L, C-reactive protein \<5 mg/L and Hemoglobin \>117 g/L. Subjects will be randomized in two groups and their Hepcidin (sHep) and iron status markers monitored at day 1 (baseline). Subjects will receive iron supplement dosages of 60 mg with stable iron isotopes 54Fe, 57Fe, 58Fe in form of 4 mg of FeSO4. Prior administration blood samples will be collected to monitor sHep and iron status markers.

Outcome: The combined use of stable iron isotopes and a sensitive SHep assay will allow for better understanding of the iron-hepcidin relationship and this may enable design of more effective OIS regimens.


Eligibility criteria: Inclusion Criteria:

* Generally healthy, no blood donation in the last 4 months, not pregnant, not lactating, not taking vitamin and mineral supplements 2 weeks prior the study, non smoker, weight \<65 Kg, BMI between 18 and 25.
* No anemia (defined as 11.7 g/dl, Serum ferritin level \< 20 microgram/L).

Primary outcomes:
measure: Iron absorption of stable isotopic tracers.
timeFrame: 14 days
Secondary outcomes:
measure: Iron status
timeFrame: 14 days
measure: Inflammatory status
timeFrame: 14 days
measure: Hepcidin level
timeFrame: 14 days
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: ETH Zürich, Laboratory of Human Nutrition
state: ZH
Study officials:
affiliation: ETH Zürich, Laboratory of Human Nutrition
name: Diego Moretti, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9. doi: 10.1182/blood-2015-05-642223. Epub 2015 Aug 19.