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

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hanna von Siebenthal; Phone Number: +41 44 632 53 73; Email: hanna.vonsiebenthal@hest.ethz.ch

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
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

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 (daily dosing, alternate-day dosing, every third-day dosing)

Dietary supplement: Labeled iron solution (60mg and 120mg Ferrous Sulfate); 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.

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 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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): December 1, 2019

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): August 30, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency
• 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