Alternate Day vs. Daily Iron Supplementation in Iron Depleted Women

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Iron-deficiency, Iron Deficiency Anemia

Intervention / Treatment
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* Dietary Supplement: Consecutive Day Dosing
* Dietary Supplement: Alternate Day Dosing


Participation Criteria
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Eligibility Criteria
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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.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Consecutive Day Dosing<br>100 mg iron as FeSO4 daily for 3 months, followed by matched placebo daily for 3 months. | Dietary Supplement: Consecutive Day Dosing<br>* 100 mg iron as FeSO4 daily for 3 months, followed by matched placebo daily for 3 months.<br>|
| Experimental: Alternate Day Dosing<br>100 mg iron as FeSO4 and matched placebo on alternating days for 6 months. | Dietary Supplement: Alternate Day Dosing<br>* 100 mg iron as FeSO4 and matched placebo on alternating days for 6 months.<br>|

What is the study measuring?
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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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dosing regimen, iron supplementation, iron sulfate, women of reproductive age