Iron Supplementation for Iron-Deficiency Anemia

Overseen By Kathleen A Groesch, MS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Southern Illinois University

Disqualifiers: Severe IDA, Hemoglobinopathy, Gastric ulcers, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This will be a randomized clinical trial. Enrolled subjects will be randomized (1:1) into two study arms to receive either daily (Group 1) or alternate day (Group 2) supplementation with one oral pill containing ferrous sulfate with an equivalent elemental iron dose of 65 mg per pill.

Is iron supplementation with ferrous sulfate safe for humans?

Ferrous sulfate, a common form of iron supplement, can cause side effects like diarrhea, increased risk of infections, and gut inflammation. However, a study found that a wax-matrix form of ferrous sulfate had fewer side effects compared to conventional tablets, with 81% of participants experiencing no severe or moderate side effects. ^{1 2}

How does the drug ferrous sulfate differ from other treatments for iron-deficiency anemia?

Ferrous sulfate is a common oral iron supplement used to treat iron-deficiency anemia by providing elemental iron, which is essential for producing hemoglobin (the protein in red blood cells that carries oxygen). It is often prescribed due to its availability and cost-effectiveness, but adherence can be an issue due to side effects like gastrointestinal discomfort. ^{3 4 5 6 7}

Research Team

Yahia Zeino, MD

Principal Investigator

Southern Illinois University School of Medicine

Eligibility Criteria

This trial is for pregnant individuals diagnosed with iron deficiency anemia. Participants should be willing to take oral iron supplements and have no health conditions that would interfere with the study.

Inclusion Criteria

Pregnant patients will be enrolled at less than 30 weeks gestational age (GA) with laboratory confirmed IDA (hemoglobin under 10.5 g/dL and ferritin under 15 mcg/L)

Exclusion Criteria

I am under 18 years old.

I need a blood transfusion or IV iron for my severe iron deficiency anemia.

I have ulcerative colitis, Crohn's disease, or gastric ulcers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment

Baseline visit where subjects undergo a blood draw to assess hemoglobin, ferritin, and sTfR levels

1 day

1 visit (in-person)

Treatment

Participants receive either daily or alternate day oral iron supplementation for iron deficiency anemia

8 weeks

Regular follow-up visits as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ferrous Sulfate

Trial Overview The study is testing if taking iron pills every other day (Group 2) is as effective as taking them daily (Group 1) in treating anemia during pregnancy. Each participant will receive a pill containing ferrous sulfate, providing 65 mg of elemental iron.

Participant Groups

Group I: 2) Alternate daily dose of ferrous sulfate with an equivalent elemental iron dose of 65 mg per pill Experimental Treatment 1 Intervention

alternate day (Group 2) supplementation with one oral pill containing ferrous sulfate with an equivalent elemental iron dose of 65 mg per pill

Group II: 1) Daily dose of ferrous sulfate with an equivalent elemental iron dose of 65 mg per pill Experimental Treatment 1 Intervention

daily (Group 1) supplementation with one oral pill containing ferrous sulfate with an equivalent elemental iron dose of 65 mg per pill

Who Is Running the Clinical Trial?

Southern Illinois University

Lead Sponsor

Trials

39

Recruited

16,200+

Findings from Research

The 'Safe Iron Study' is the first clinical trial to evaluate the safety and efficacy of novel iron supplements, comparing them to traditional ferrous sulfate in healthy adults, aiming to address the adverse effects associated with current iron treatments.

The study will assess whether these new iron forms can improve iron status without increasing risks of malaria, bacterial infections, or gut inflammation, potentially leading to safer options for treating iron deficiency and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective delivery of supplemental iron to healthy older adults: The double-blind, randomized, placebo-controlled trial protocol of the Safe Iron Study. Lewis, ED., Wu, D., Mason, JB., et al.[2023]

Oral iron supplementation with ferrous sulfate (FeSO₄) leads to significantly higher levels of non-transferrin-bound iron (NTBI) in the bloodstream compared to other iron compounds, which raises safety concerns for young children with malaria.

In contrast, iron compounds like sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and iron polymaltose show negligible NTBI responses, suggesting they may be safer alternatives for iron supplementation in areas where malaria is prevalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. Schümann, K., Solomons, NW., Romero-Abal, ME., et al.[2022]

In a study analyzing 287 clinical records of young infants, ferrous sulfate was prescribed as a preventive therapy for iron deficiency anemia in 100% of cases, indicating strong adherence to the recommendation for iron supplementation.

However, only 18.1% of the prescriptions met all five criteria for adequacy, with the lowest compliance seen in dosage (29.2%), highlighting the need for improved practices in prescribing iron supplements to ensure effective prevention of anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the prescription pattern of ferrous sulfate as a therapy for preventing iron deficiency anemia in infants. Vásquez-Guzmán, RA., Solano-Ceh, A., Villarreal-Ríos, E., et al.[2022]

In a study of 133 non-anemic children receiving ferrous sulfate supplements for six months, 56.7% showed high adherence to the supplementation, while 43.3% had low adherence, indicating a significant gap in compliance.

Both high and low adherence groups demonstrated limited knowledge about anemia and its prevention, highlighting the need for better education and support from health services to improve adherence and understanding of iron supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Problems of adherence to the program of prevention of iron deficiency anemia and supplementation with iron salts in the city of Viçosa, Minas Gerais, Brazil]. Azeredo, CM., Cotta, RM., da Silva, LS., et al.[2019]

Pediatricians in Rosario view iron deficiency anemia as a significant health issue, primarily linked to poor dietary quality, and they follow national standards in their clinical practice.

To improve management of iron deficiency anemia, pediatricians suggest implementing workshops on anemia and providing more palatable iron supplements to enhance adherence among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The perspective of primary health care pediatricians regarding childhood anemia and iron supplementation. Sguassero, Y., Guerrero, MM., Romero, M.[2022]

In a study of 514 pregnant Israeli women, those who took a daily supplement of ferrous sulfate (100 mg elemental iron) experienced significantly less reduction in hemoglobin levels compared to those who did not take the supplement, indicating its efficacy in preventing anemia during pregnancy.

Despite the benefits, 40 out of the 200 women on the iron supplement developed anemia after the fifth month, suggesting that while the supplement is helpful, monitoring is necessary as pregnancy progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anemia of pregnancy: evaluation of the effectiveness of routine dietary supplementation program in an Israeli community. Palgi, A., Levi, S., Reshef, A.[2019]

Iron supplementation (100 mg/day) significantly improved hemoglobin levels and antioxidant enzyme activity in 117 anemic women over 100 days, indicating its efficacy in treating iron deficiency anemia.

However, the treatment also increased oxidative stress markers and caused more side effects in women with mild anemia compared to those with moderate or severe anemia, suggesting that iron supplementation should be tailored to individual needs rather than given universally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral iron supplementation leads to oxidative imbalance in anemic women: a prospective study. Tiwari, AK., Mahdi, AA., Chandyan, S., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safe and effective delivery of supplemental iron to healthy older adults: The double-blind, randomized, placebo-controlled trial protocol of the Safe Iron Study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. [2022]

3. Mexico pubmed.ncbi.nlm.nih.gov

Evaluation of the prescription pattern of ferrous sulfate as a therapy for preventing iron deficiency anemia in infants. [2022]

4. Brazil pubmed.ncbi.nlm.nih.gov

[Problems of adherence to the program of prevention of iron deficiency anemia and supplementation with iron salts in the city of Viçosa, Minas Gerais, Brazil]. [2019]

5. Argentina pubmed.ncbi.nlm.nih.gov

The perspective of primary health care pediatricians regarding childhood anemia and iron supplementation. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Anemia of pregnancy: evaluation of the effectiveness of routine dietary supplementation program in an Israeli community. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Oral iron supplementation leads to oxidative imbalance in anemic women: a prospective study. [2013]