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

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

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.

Study Overview

• Status: Completed
• Conditions: Iron Deficiency Anemia of Pregnancy
• Intervention / Treatment: Dietary supplement: Labeled iron solution (60mg and 120mg Ferrous Fumarate)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Nakhon Pathom
    • Salaya, Nakhon Pathom, Thailand, 73170
      • Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• gestational week 14-16 at study start
• singleton pregnancy
• Serum ferritin SF <60 µg/L
• non-anemic or mildly anemic, defined as hemoglobin (Hb) >10 g/dL
• female aged 18-45 years
• healthy Thai woman

Exclusion Criteria:

• acute or chronic disease
• taking medications that could influence iron absorption
• smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: oral iron supplementation; Participants go through 3 cycles of oral iron Supplementation (60mg daily vs alternate day dosing, 120mg daily vs alternate day dosing, 120mg daily vs every third-day dosing)

Dietary supplement: Labeled iron solution (60mg and 120mg Ferrous Fumarate); 3 doses of 60mg iron as ferrous fumarate are given on one consecutive day and one alternate day (e.g., days 1, 2, 4); 3 doses of 120mg iron as ferrous fumarate are given on one consecutive and one alternate day (e.g., days 20, 21, 23); 3 doses of 120mg iron as ferrous fumarate 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 200ml deionized water (57Fe, 58Fe or 54Fe). Participants will be randomly assigned to start with 60mg iron daily vs alternate day dosing, 120mg daily vs alternate day dosing or 120mg daily vs every-third day dosing.

What is the study measuring?

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 60mg daily vs alternate day cycle	Day 18
Fractional iron absorption in %	Erythrocyte incorporation of stable iron isotopes 14 days after the last supplement intake of the 120mg daily vs alternate day cycle	Day 35
Fractional iron absorption in %	Erythrocyte incorporation of stable iron isotopes 14 days after the last supplement intake of the 120mg daily vs every third day cycle	Day 53
Total iron absorption in %	Fractional iron absorption measured from the 60mg daily vs alternate day cycle multiplied by the dose	Day 18
Total iron absorption in %	Fractional iron absorption measured from the 120mg daily vs alternate day cycle multiplied by the dose	Day 35
Total iron absorption in %	Fractional iron absorption measured from the 120mg daily vs every third day cycle multiplied by the dose	Day 53
Serum Hepcidin	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Serum Hepcidin	in the morning before second supplement intake of the 60mg daily vs alternate day cycle	Day 2
Serum Hepcidin	in the morning before third supplement intake of the 60mg daily vs alternate day cycle	Day 4
Serum Hepcidin	in the morning before first supplement intake of 120mg daily vs alternate day cycle	Day 18
Serum Hepcidin	in the morning before second supplement intake of 120mg daily vs alternate day cycle	Day 19
Serum Hepcidin	in the morning before third supplement intake of 120mg daily vs alternate day cycle	Day 21
Serum Hepcidin	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Serum Hepcidin	in the morning before second supplement intake of the 120mg daily vs every third day cycle	Day 36
Serum Hepcidin	in the morning before third supplement intake of the 120mg daily vs every third day cycle	Day 39
Serum Hepcidin	in the morning 14 days after last supplement intake the 120mg daily vs every third day cycle	Day 53

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Ferritin (SF)	in the morning before first supplement intake	Screening
Serum Ferritin (SF)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Serum Ferritin (SF)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Serum Ferritin (SF)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Serum Ferritin (SF)	in the morning 14 days after last supplement intake of the 120mg daily vs every third day cycle	Day 53
Hemoglobin (Hb)	in the morning before first supplement intake	Screening
Hemoglobin (Hb)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Hemoglobin (Hb)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Hemoglobin (Hb)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Hemoglobin (Hb)	in the morning 14 days after last supplement intake of the 120mg daily vs every third day cycle	Day 53
Soluble transferrin receptor (sTfR)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Soluble transferrin receptor (sTfR)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Soluble transferrin receptor (sTfR)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Soluble transferrin receptor (sTfR)	in the morning 14 days after last supplement intake of the 120mg daily vs every third day cycle	Day 53
C-reactive protein (CRP)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
C-reactive protein (CRP)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
C-reactive protein (CRP)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
C-reactive protein (CRP)	in the morning 14 days after last supplement intake of the 120mg daily vs every third day cycle	Day 53
Alpha-1-acid glycoprotein (AGP)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Alpha-1-acid glycoprotein (AGP)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Alpha-1-acid glycoprotein (AGP)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Alpha-1-acid glycoprotein (AGP)	in the morning 14 days after last supplement intake of the 120mg daily vs every third day cycle	Day 53
Serum Hepcidin	in the afternoon after first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Serum Hepcidin	in the afternoon after first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Serum Hepcidin	in the afternoon 14 days after third supplement intake of the 120mg daily vs every third day cycle	Day 53
Serum Iron (SFe)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Serum Iron (SFe)	in the morning before second supplement intake of the 60mg daily vs alternate day cycle	Day 2
Serum Iron (SFe)	in the morning before third supplement intake of the 60mg daily vs alternate day cycle	Day 4
Serum Iron (SFe)	in the afternoon after first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Serum Iron (SFe)	in the morning before the first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Serum Iron (SFe)	in the morning before the second supplement intake of the 120mg daily vs alternate day cycle	Day 19
Serum Iron (SFe)	in the morning before the third supplement intake of the 120mg daily vs alternate day cycle	Day 21
Serum Iron (SFe)	in the afternoon after the first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Serum Iron (SFe)	in the morning before the first supplement intake of the 120mg daily vs every third day cycle	Day 35
Serum Iron (SFe)	in the morning before the second supplement intake of the 120mg daily vs every third day cycle	Day 36
Serum Iron (SFe)	in the morning before the third supplement intake of the 120mg daily vs every third day cycle	Day 39
Serum Iron (SFe)	in the morning 14 days after the last supplement intake of the 120mg daily vs every third day cycle	Day 53
Serum Iron (SFe)	in the afternoon 14 days after the last supplement intake of the 120mg daily vs every third day cycle	Day 53
Total Iron Binding Capacity (TIBC)	in the morning before first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Total Iron Binding Capacity (TIBC)	in the morning before second supplement intake of the 60mg daily vs alternate day cycle	Day 2
Total Iron Binding Capacity (TIBC)	in the morning before third supplement intake of the 60mg daily vs alternate day cycle	Day 4
Total Iron Binding Capacity (TIBC)	in the afternoon after first supplement intake of the 60mg daily vs alternate day cycle	Day 1
Total Iron Binding Capacity (TIBC)	in the morning before first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Total Iron Binding Capacity (TIBC)	in the morning before second supplement intake of the 120mg daily vs alternate day cycle	Day 19
Total Iron Binding Capacity (TIBC)	in the morning before third supplement intake of the 120mg daily vs alternate day cycle	Day 21
Total Iron Binding Capacity (TIBC)	in the afternoon after first supplement intake of the 120mg daily vs alternate day cycle	Day 18
Total Iron Binding Capacity (TIBC)	in the morning before first supplement intake of the 120mg daily vs every third day cycle	Day 35
Total Iron Binding Capacity (TIBC)	in the morning before second supplement intake of the 120mg daily vs every third day cycle	Day 36
Total Iron Binding Capacity (TIBC)	in the morning before third supplement intake of the 120mg daily vs every third day cycle	Day 39
Total Iron Binding Capacity (TIBC)	in the morning 14 after last supplement intake of the 120mg daily vs every third day cycle	Day 53
Total Iron Binding Capacity (TIBC)	in the afternoon 14 after last supplement intake of the 120mg daily vs every third day cycle	Day 53

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: Mahidol University

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2019
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: August 27, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Iron Deficiencies; Physiological Effects of Drugs; Trace Elements; Micronutrients; Ferrous fumarate
• Other Study ID Numbers: TIPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No