Defining a Dosing Regimen With Maximal Absorption for Oral Iron Supplementation During Pregnancy

Study Overview
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Brief Summary
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Iron deficiency anemia (IDA) is common during pregnancy and has adverse effects on the mother, fetus and newborn. Oral iron supplements are usually recommended to prevent ID/IDA during pregnancy. The aim of this study is to define an iron supplementation schedule with maximal absorption using serum hepcidin profiles and stable iron isotopes in pregnant women. In this randomized, open-label trial, fractional and total iron absorption will be compared from daily dosing with 60 mg iron versus alternate day and every third day dosing with 120 mg iron in pregnant Thai women with low iron stores (n=28) during their second trimester of pregnancy. This study could have wide impact, providing the evidence base for revised, improved recommendations for iron supplementation during pregnancy.

Official Title
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Optimizing Oral Iron Supplementation Regimens During Pregnancy Using Serum Hepcidin Profiles and Iron Stable Isotopes: Defining a Dosing Regimen With Maximal Absorption and Minimal Gastrointestinal Side Effects

Conditions
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Iron Deficiency Anemia of Pregnancy

Intervention / Treatment
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* Dietary Supplement: Labeled iron solution (60mg and 120mg Ferrous Sulfate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational week 14-16 singleton pregnancy iron depleted, defined as serum ferritin SF <30 µg/L non-anemic, defined as hemoglobin (Hb) >11g/dL Exclusion Criteria: acute or chronic disease taking medications that could influence iron absorption smoking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: each subject acts as her own control by going through all the three supplementation cycles. Women will be randomly assigned to start with the daily, every other day or every third day supplementation cycle.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral iron supplementation<br>Participants go through 3 cycles of oral iron Supplementation (daily dosing, alternate-day dosing, every third-day dosing) | Dietary Supplement: Labeled iron solution (60mg and 120mg Ferrous Sulfate)<br>* 3 doses of 60mg iron as FeSO4 are given on 3 consecutive days (e.g., days 1-3); 3 doses of 120mg iron as FeSO4 are given on one consecutive and one alternate day (e.g., days 20, 21, 23); 3 doses of 120mg iron as FeSO4 are given on one consecutive and one 3rd day (e.g., days 37, 38, 41). Iron doses are labeled with 4mg of a stable isotope in 100ml deionized water (57Fe, 58Fe or 54Fe). Participants will be randomly assigned to start with daily, alternate-day or every-third day dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional iron absorption in % | Erythrocyte incorporation of stable iron isotopes 14 days after the last supplement intake of the consecutive day cycle | Day 17 | 
| Fractional iron absorption in % | Erythrocyte incorporation of stable iron isotopes 14 days after the last supplement intake of the alternate day cycle | Day 34 | 
| Fractional iron absorption in % | Erythrocyte incorporation of stable iron isotopes 14 days after the last supplement intake of the every third day cycle | Day 52 | 
| Total iron absorption in % | Fractional iron absorption measured from consecutive day cycle multiplied by the dose | Day 17 | 
| Total iron absorption in % | Fractional iron absorption measured from alternate day cycle multiplied by the dose | Day 34 | 
| Total iron absorption in % | Fractional iron absorption measured from every third day cycle multiplied by the dose | Day 52 | 
| Serum Hepcidin | in the morning a day before first supplement intake of consecutive day cycle | Day 0 | 
| Serum Hepcidin | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| Serum Hepcidin | in the morning before second supplement intake of consecutive day cycle | Day 2 | 
| Serum Hepcidin | in the morning before third supplement intake of consecutive day cycle | Day 3 | 
| Serum Hepcidin | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| Serum Hepcidin | in the morning before second supplement intake of alternate day cycle | Day 18 | 
| Serum Hepcidin | in the morning before third supplement intake of alternate day cycle | Day 20 | 
| Serum Hepcidin | in the morning before first supplement intake of every third day cycle | Day 34 | 
| Serum Hepcidin | in the morning before second supplement intake of every third day cycle | Day 35 | 
| Serum Hepcidin | in the morning before third supplement intake of every third day cycle | Day 38 | 
| Serum Hepcidin | in the morning 14 days after last supplement intake of every third day cycle | Day 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Ferritin (SF) | in the morning 1 day before first supplement intake of consecutive day cycle | Day 0 | 
| Serum Ferritin (SF) | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| Serum Ferritin (SF) | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| Serum Ferritin (SF) | in the morning before first supplement intake of every third day cycle | Day 34 | 
| Serum Ferritin (SF) | in the morning 14 days after last supplement intake of every third day | Day 52 | 
| Hemoglobin (Hb) | in the morning 1 day before first supplement intake of consecutive day cycle | Day 0 | 
| Hemoglobin (Hb) | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| Hemoglobin (Hb) | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| Hemoglobin (Hb) | in the morning before first supplement intake of every third day cycle | Day 34 | 
| Hemoglobin (Hb) | in the morning 14 days after last supplement intake of every third day cycle | Day 52 | 
| Soluble transferrin receptor (sTfR) | in the morning 1 day before first supplement intake of consecutive day cycle | Day 0 | 
| Soluble transferrin receptor (sTfR) | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| Soluble transferrin receptor (sTfR) | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| Soluble transferrin receptor (sTfR) | in the morning before first supplement intake of every third day cycle | Day 34 | 
| Soluble transferrin receptor (sTfR) | in the morning 14 days after last supplement intake of every third day cycle | Day 52 | 
| C-reactive protein (CRP) | in the morning 1 day before first supplement intake of consecutive day cycle | Day 0 | 
| C-reactive protein (CRP) | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| C-reactive protein (CRP) | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| C-reactive protein (CRP) | in the morning before first supplement intake of every third day cycle | Day 34 | 
| C-reactive protein (CRP) | in the morning 14 days after last supplement intake of every third day cycle | Day 52 | 
| Alpha-1-acid glycoprotein (AGP) | in the morning 1 day before first supplement intake of consecutive day cycle | Day 0 | 
| Alpha-1-acid glycoprotein (AGP) | in the morning before first supplement intake of consecutive day cycle | Day 1 | 
| Alpha-1-acid glycoprotein (AGP) | in the morning before first supplement intake of alternate day cycle | Day 17 | 
| Alpha-1-acid glycoprotein (AGP) | in the morning before first supplement intake of every third day cycle | Day 34 | 
| Alpha-1-acid glycoprotein (AGP) | in the morning 14 days after last supplement intake of every third day cycle | Day 52 | 
| Serum Hepcidin | in the afternoon a day before first supplement intake of consecutive day cycle | Day 0 | 
| Serum Hepcidin | in the afternoon after first supplement intake of consecutive day cycle | Day 1 | 
| Serum Hepcidin | in the afternoon after second supplement intake of consecutive day cycle | Day 2 | 
| Serum Hepcidin | in the afternoon after third supplement intake of consecutive day cycle | Day 3 | 
| Serum Hepcidin | in the afternoon after first supplement intake of alternate day cycle | Day 17 | 
| Serum Hepcidin | in the afternoon after second supplement intake of alternate day cycle | Day 18 | 
| Serum Hepcidin | in the afternoon after third supplement intake of alternate day cycle | Day 20 | 
| Serum Hepcidin | in the afternoon after first supplement intake of every third day cycle | Day 34 | 
| Serum Hepcidin | in the afternoon after second supplement intake of every third day cycle | Day 35 | 
| Serum Hepcidin | in the afternoon after third supplement intake of every third day cycle | Day 38 | 
| Serum Hepcidin | in the afternoon 14 days after third supplement intake of every third day cycle | Day 52 |