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

This study has been completed.
Sponsor:
Collaborators:
ETH Zürich
University Hospital, Zürich
Information provided by (Responsible Party):
Swiss Federal Institute of Technology
ClinicalTrials.gov Identifier:
NCT01785407
First received: February 1, 2013
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

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).


Condition Intervention
Iron Deficiency
Anemia
Iron Deficiency Anemia
Dietary Supplement: Iron Supplement (Ferrous Sulfate Dried)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Using Stable Iron Isotopic Techniques and Serum Hepcidin Profiles to Optimize Iron Supplementation

Resource links provided by NLM:


Further study details as provided by Swiss Federal Institute of Technology:

Primary Outcome Measures:
  • Iron bio-availability from Oral Iron Supplements (%) [ Time Frame: three weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: three weeks ] [ Designated as safety issue: No ]
    Serum Hepcidin levels will be measured in participating subjects in concomitance with iron bioavailability.


Enrollment: 25
Study Start Date: February 2013
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: Ferrous Sulfate (dried)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01785407

Locations
Switzerland
Laboratory of Human Nutrition
Zürich, Switzerland, 8092
Sponsors and Collaborators
Swiss Federal Institute of Technology
ETH Zürich
University Hospital, Zürich
Investigators
Principal Investigator: Diego Moretti, PhD ETH Zürich
  More Information

Publications:
Responsible Party: Swiss Federal Institute of Technology
ClinicalTrials.gov Identifier: NCT01785407     History of Changes
Other Study ID Numbers: EK 2012-N-44
Study First Received: February 1, 2013
Last Updated: November 8, 2013
Health Authority: Switzerland: Laws and standards

Keywords provided by Swiss Federal Institute of Technology:
Iron bio availability
Hepcidin
Iron absorption

Additional relevant MeSH terms:
Anemia
Anemia, Iron-Deficiency
Anemia, Hypochromic
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Hepcidins
Iron
Anti-Infective Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on November 25, 2014