Using Stable Iron Isotopic Techniques and Serum Hepcidin Profiles to Optimize Iron Supplementation

Sponsor

Swiss Federal Institute of Technology (Other)

Overall Status

Completed

CT.gov ID

NCT01785407

Collaborator

ETH Zürich (Other), University Hospital, Zürich (Other)

Enrollment

Location

Arms

3.9

Duration (Months)

6.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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: it may be in the range of 24 to 96 hr. 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.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia Iron Deficiency Anemia	Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried)	N/A

Detailed Description

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: it may be in the range of 24 to 96 hr. 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 the duration and magnitude of the Fe induced Hepcidin rise form a single iron dose while determining its bioavailability and 2) Compare the bioavailability of a single dose to iron supplements consumed one after the other (two dosages). 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 40, 80, 160 and 240 mg in either single or as two consecutive dosages with stable iron isotopes 54Fe, 57Fe, 58Fe in form of 4 mg of iron sulfate (FeSO4). Prior administration blood samples will be collected at 8:00, 12:00 and 16:00 to monitor sHep and iron status markers, these measurements will be repeated on the days of supplement administration. On the following days, sHep will be measured at 8:00 to quantify the duration of the iron induced hepcidin rise. In the second week, subjects receiving a single Fe dose on week 1 will receive two consecutive dosages and vice versa, while the same sampling scheme as in week one will be applied. On day 23, a last blood sample will be collected and iron incorporation of stable isotopic labels will be measured from the different dosages administered.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Using Stable Iron Isotopic Techniques and Serum Hepcidin Profiles to Optimize Iron Supplementation

Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 80 mg FeSO4	Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried) Iron supplements of varying concentration will be administered to the four groups in the study. Iron bioavailability from the supplements will be assessed. Other Names: Ferrous Sulfate (dried)
Active Comparator: 40 mg FeSO4 40 mg FeSO4	Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried) Iron supplements of varying concentration will be administered to the four groups in the study. Iron bioavailability from the supplements will be assessed. Other Names: Ferrous Sulfate (dried)
Active Comparator: 160 mg FeSO4	Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried) Iron supplements of varying concentration will be administered to the four groups in the study. Iron bioavailability from the supplements will be assessed. Other Names: Ferrous Sulfate (dried)
Active Comparator: 240 mg FeSO4	Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried) Iron supplements of varying concentration will be administered to the four groups in the study. Iron bioavailability from the supplements will be assessed. Other Names: Ferrous Sulfate (dried)

Outcome Measures

Primary Outcome Measures

Iron bio-availability from Oral Iron Supplements (%) [three weeks]
Iron bioavailability will be assessed with stable isotopic labels. The shift in the isotopic ratio in human whole blood 14 days after administration will be measured with Inductively coupled plasma mass spectrometry (ICP-MS).

Secondary Outcome Measures

Hepcidin [three weeks]
Serum Hepcidin levels will be measured in participating subjects in concomitance with iron bioavailability.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

BMI 17-25
No anemia
Low iron stores defined as Serum Ferritin < 20 micrograms/L
No blood donation in in the last 4 months
No intake of vitamin and mineral supplements 2 weeks prior and during the study

Exclusion Criteria:

Chronic, metabolic, gastrointestinal diseases
Taking medication
Participation to clinical trials in the last 30 days.
Previous participation to iron bio availability studies with stable isotopic labels.