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

Study Overview
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Brief Summary
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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.

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: a Randomized Controlled Trial in the Philippines

Conditions
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Iron-deficiency

Intervention / Treatment
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* Dietary Supplement: daily ferrous sulfate
* Dietary Supplement: alternate day ferrous sulfate


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 11-15.5 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

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>This arm will daily receive iron capsules for 3 months, followed by daily placebo capsules for 3 months. | Dietary Supplement: daily ferrous sulfate<br>* Daily intake of 100 mg ferrous sulfate capsules for 3 months<br>|
| Experimental: Alternate Day Dosing<br>This arm will receive iron capsules alternating with placebo capsules for 6 months. | Dietary Supplement: alternate day ferrous sulfate<br>* Alternate day intake of 100 mg ferrous sulfate capsules 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 93 | 
| 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 | 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 |