Alternate Day vs. Daily Iron Supplementation in Iron Depleted Women in the Philippines

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: a Randomized Controlled Trial in the Philippines

Iron is very important for our body and performs vital tasks. Iron deficiency is a worldwide health problem. The prevalence of anemia in women of reproductive age in Southeast Asia is estimated to be 46.6% in 2019, with iron deficiency being one of the main reasons for anemia. There are different approaches to treat iron deficiency. One of them is the use of iron supplements. Recommended iron supplement treatments today often differ in dose, regimen and length. Experts recommend a dose of 80-200 mg of iron taken either daily or on several days per week, depending on the severity of the iron deficiency (with or without anemia). From certain guidelines lower amounts of iron are also recommended, as this could lead to fewer side effects.Previous studies have shown that both daily and multiple days per week administration can be effective in treating iron deficiency. Recently, several successive iron supplementation studies in Zurich showed that 24 h after ingestion of an oral dose of >60mg iron, the absorption of iron in the body is impaired. In addition it was measured that iron supplements taken only every other day instead of every day are absorbed about 30-50% better and have fewer side effects. Little is known about the long-term effect of this alternating regimen on iron status and side effects.With this 6-months study in the Philippines, the investigators want to compare two different supplementation regimens with oral iron to see if there is any difference in the iron status, intestinal inflammation levels, and side effects, and therefore if it would be better to take the iron supplements every 2 days instead of daily.

Study Overview

• Status: Terminated
• Conditions: Iron-deficiency
• Intervention / Treatment: Dietary supplement: daily ferrous sulfate; Dietary supplement: alternate day ferrous sulfate

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Philippines
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1015
      • University of Santo Tomas Hospital

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 11-15.5 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

Exclusion Criteria:

• Elevated CRP > 5 mg/L
• Any metabolic, gastrointestinal, kidney or chronic disease such as diabetes, renal failure, hepatic dysfunction, hepatitis, hypertension, cancer or cardiovascular diseases (according to the participants own statement) affecting iron metabolism,
• Use of medication which may interfere with iron absorption, gut physiology and iron metabolism
• Consumption of iron supplements within 2 weeks prior to study start and of additional iron supplements during the study period
• Difficulties with blood sampling,
• Known hypersensitivity or allergy to iron or placebo capsules in the given amount (ferrous sulfate, mannitol, silica)
• Pregnancy, breastfeeding
• Known or suspected non-compliance, drug or alcohol abuse
• Cigarette smokers

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; This arm will daily receive iron capsules for 3 months, followed by daily placebo capsules for 3 months.	Dietary supplement: daily ferrous sulfate; Daily intake of 100 mg ferrous sulfate capsules for 3 months
Experimental: Alternate Day Dosing; This arm will receive iron capsules alternating with placebo capsules for 6 months.	Dietary supplement: alternate day ferrous sulfate; Alternate day intake of 100 mg ferrous sulfate capsules 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	Measure Description	Time Frame
Hemoglobin (Hb)		Day 0
Hemoglobin (Hb)		Day 46
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
Hemoglobin (Hb)		Day 93
Severity of GI side effects	5 different side effects (nausea, stomach pain, constipation, diarrhea, bloating) are reported if they occur in a study app and rated "mild" or "severe", according to their judgement.	Day 90
Severity of GI side effects	5 different side effects (nausea, stomach pain, constipation, diarrhea, bloating) are reported if they occur in a study app and rated "mild" or "severe", according to their judgement.	Day 183

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: University of Oxford; St. Luke's Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2022
• Primary Completion (Actual): November 19, 2022
• Study Completion (Actual): November 19, 2022

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Deficiencies
• Other Study ID Numbers: CAPS_PH

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