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

Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01785407
• Other study ID #: EK 2012-N-44
• Status: Completed
• Phase: N/A
• First received: February 1, 2013
• Last updated: November 8, 2013
• Start date: February 2013
• Est. completion date: June 2013

Study information

• Verified date: November 2013
• Source: Swiss Federal Institute of Technology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Laws and standards
• Study type: Interventional

Clinical Trial 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.

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Iron Deficiency
• Iron Deficiency Anemia

Intervention

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.

Locations

Country	Name	City	State
Switzerland	Laboratory of Human Nutrition	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
Swiss Federal Institute of Technology	University Hospital, Zürich, University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet. 2007 Aug 11;370(9586):511-20. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Iron bio-availability from Oral Iron Supplements (%)	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).	three weeks	No
Secondary	Hepcidin	Serum Hepcidin levels will be measured in participating subjects in concomitance with iron bioavailability.	three weeks	No