Alternate Day vs. Daily Iron Supplementation in Iron Depleted Women

Comparing Oral Iron Supplementation Using Alternate-day Dosing to the Standard of Care Consecutive-day Dosing in Iron-depleted Women With or Without Mild Anemia

Iron deficiency (ID) with or without anemia is a major public health problem worldwide, especially in women of reproductive age. Iron supplementation can be an effective strategy to prevent and treat ID and iron deficiency anemia (IDA). Recent studies suggests that giving oral iron every other day would be an optimized dosing regimen with maximized absorption and a lower incidence of gastrointestinal side effects compared to consecutive day dosing. Long-term trials in which participants and investigators are blinded to the dosing interval with iron status and gastrointestinal side effects as study outcomes are needed.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Iron Deficiency Anemia
• Intervention / Treatment: Dietary supplement: Consecutive Day Dosing; Dietary supplement: Alternate Day Dosing

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8092
    • ETH Zurich; Human Nutrition Laboratory; Institute of Food, Nutrition and Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female, 18 to 45 years old,
• SF levels <25 μg/L,
• Hb levels ≥ 11 g/dL
• Normal Body Mass Index (18.5-25 kg/m2),
• In possession of a mobile phone on which the study app can be loaded,
• Signed informed consent,
• Not mandatory (only for subgroup analysis): having participated in a former stable iron isotope study in our laboratory between 1-5 y ago

Exclusion Criteria:

• Elevated CRP > 5 mg/L,
• Any metabolic, gastrointestinal, kidney or chronic disease (self-reported) affecting iron metabolism,
• Continuous/long-term use of medication, which may interfere with iron absorption, gut physiology and iron metabolism,
• Consumption of additional iron supplements over the study period,
• Consumption of iron supplements since screening,
• Difficulties with blood sampling,
• Known hypersensitivity or allergy to iron or placebo capsules in the given amount (ferrous sulfate, mannitol, silica)
• Pregnancy, breastfeeding
• Women who intend to become pregnant during the course of the study,
• Known or suspected non-compliance, drug or alcohol (more than 2 drinks/day) abuse,
• Smokers (> 1 cigarette per week),
• Participant is likely to be absent on one the study appointments,
• Inability to follow the procedures of the study, e.g. due to language problems, self-reported psychological disorders, etc. of the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Consecutive Day Dosing; 100 mg iron as FeSO4 daily for 3 months, followed by matched placebo daily for 3 months.	Dietary supplement: Consecutive Day Dosing; 100 mg iron as FeSO4 daily for 3 months, followed by matched placebo daily for 3 months.
Experimental: Alternate Day Dosing; 100 mg iron as FeSO4 and matched placebo on alternating days for 6 months.	Dietary supplement: Alternate Day Dosing; 100 mg iron as FeSO4 and matched placebo on alternating days for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Ferritin (SF)	in consecutive day group	Day 93
Serum Ferritin (SF)	in alternate day group	Day 186
Event rate of GI side effects	in consecutive day group	Day 90
Event rate of GI side effects	in alternate day group	Day 183

Secondary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin (Hb)	Day 0
Hemoglobin (Hb)	Day 46
Hemoglobin (Hb)	Day 90
Hemoglobin (Hb)	Day 139
Hemoglobin (Hb)	Day 183
Serum Ferritin (SF)	Day 0
Serum Ferritin (SF)	Day 46
Serum Ferritin (SF)	Day 93
Serum Ferritin (SF)	Day 139
Serum Ferritin (SF)	Day 186
Serum Transferrin Receptor (sTfR)	Day 0
Serum Transferrin Receptor (sTfR)	Day 46
Serum Transferrin Receptor (sTfR)	Day 93
Serum Transferrin Receptor (sTfR)	Day 139
Serum Transferrin Receptor (sTfR)	Day 186
Total iron binding capacity (TIBC)	Day 0
Total iron binding capacity (TIBC)	Day 93
Total iron binding capacity (TIBC)	Day 186
Serum Iron (SFe)	Day 0
Serum Iron (SFe)	Day 93
Serum Iron (SFe)	Day 186
C-Reactive Protein (CRP)	Day 0
C-Reactive Protein (CRP)	Day 46
C-Reactive Protein (CRP)	Day 93
C-Reactive Protein (CRP)	Day 139
C-Reactive Protein (CRP)	Day 186
Alpha-1-acid Glycoprotein (AGP)	Day 0
Alpha-1-acid Glycoprotein (AGP)	Day 46
Alpha-1-acid Glycoprotein (AGP)	Day 93
Alpha-1-acid Glycoprotein (AGP)	Day 139
Alpha-1-acid Glycoprotein (AGP)	Day 186
Intestinal Fatty Acid-binding Protein (I-FABP)	Day 0
Intestinal Fatty Acid-binding Protein (I-FABP)	Day 90
Intestinal Fatty Acid-binding Protein (I-FABP)	Day 183
Calprotectin	Day 0
Calprotectin	Day 90
Calprotectin	Day 183
Hepcidin	Day 0
Hepcidin	Day 46
Hepcidin	Day 90
Hepcidin	Day 139
Hepcidin	Day 183
Event rate of GI side effects	Day 90
Event rate of GI side effects	Day 183
Incidence of GI side effects	Day 90
Incidence of GI side effects	Day 183
Event proportion of GI side effects	Day 90
Event proportion of GI side effects	Day 183
Severity of GI side effects	Day 90
Severity of GI side effects	Day 183
Fecal blood losses	Day 0
Fecal blood losses	Day 90
Fecal blood losses	Day 183
Iron absorption from supplements	Day 90
Iron absorption from supplements	Day 183

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Investigators: Principal Investigator: Nicole Stoffel, Dr., Human Nutrition Laboratory, ETH Zuerich

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): December 8, 2022

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: October 22, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

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

More Information

Terms related to this study

• Keywords: iron supplementation; women of reproductive age; dosing regimen; iron sulfate
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Iron Deficiencies
• Other Study ID Numbers: CAPS_CH

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