Iron Supplementation for Blood Donors

(UH3BLIS Trial)

Overseen By Susan E Telke, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Iron supplements

Disqualifiers: Very low haemoglobin

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking a low dose of iron for six months can help individuals with low hemoglobin (a protein in red blood cells) successfully donate blood later. Participants will either receive iron supplements (low-dose elemental iron) or receive nutrition advice, which is the current standard care. The main goal is to determine if those taking iron can donate at least once in a year. This trial suits individuals who have been turned away from donating blood due to low hemoglobin but are otherwise healthy and willing to participate for a year. As an unphased trial, it offers a chance to contribute to important research that could improve blood donation eligibility for many.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have used iron supplements in the past month, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that low-dose iron supplements are generally safe for most people. One study found that taking 30 mg or 60 mg of iron daily or every other day safely increased iron levels in blood donors. Another study found that these supplements helped blood donors with normal hemoglobin levels recover their iron levels faster than those who didn't take supplements.

These findings suggest that most people tolerate low-dose iron taken daily. However, like any supplement, iron can cause mild side effects, particularly in the digestive system, such as stomach upset or constipation. Participants should report any side effects during the trial so they can be addressed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about low dose elemental iron supplementation for blood donors because it offers a potentially safer and more efficient way to restore iron levels compared to higher dose supplements or dietary changes. Most treatments for iron deficiency in blood donors involve taking larger doses of iron, which can lead to side effects like stomach upset. The low dose approach might reduce these side effects while still effectively replenishing iron. This treatment could make the donation process more comfortable and accessible for regular donors, encouraging more frequent donations and improving overall donor health.

What evidence suggests that low dose elemental iron might be an effective treatment for blood donors with low haemoglobin?

Research has shown that low-dose iron supplements, which participants in this trial may receive, can significantly benefit blood donors with low hemoglobin levels. Studies have found that these supplements help donors recover more quickly after giving blood, particularly those with low ferritin levels, a protein that stores iron. One study found that daily iron intake greatly reduced the number of donors unable to donate due to low hemoglobin. Another study showed that taking 60 mg of iron daily improved iron levels without major side effects. These findings suggest that low-dose iron supplements can help restore hemoglobin levels, facilitating future blood donations. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-60, weighing at least 50kg, who meet the physical criteria for blood donation but were deferred due to low haemoglobin. They must understand English, Twi, Ewe, or Ga and be willing to stay in the study for its full length.

Inclusion Criteria

I plan to stay in the study for its full duration.

You have successfully completed the National Blood Supply Group's pre-donation screening questionnaire.

Your non-contact forehead temperature must be below 37.5°C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 6 months of low-dose iron supplementation or standard nutrition counseling

6 months

Monthly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up phone calls at 4 weekly intervals

12 months

Phone calls every 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Elemental Iron

Trial Overview The trial compares a group taking low-dose iron supplements daily with those receiving only nutrition counseling after being deferred from blood donation due to low haemoglobin. Success is measured by their ability to donate blood within a year.

How Is the Trial Designed?

Group I: Iron Supplementation Experimental Treatment 1 Intervention

Group II: Standard of Care Active Control 1 Intervention

Low Dose Elemental Iron is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Elemental iron for:

• Iron deficiency anemia
• Iron deficiency

Approved in European Union as Elemental iron for:

• Iron deficiency anemia
• Iron deficiency

Approved in Canada as Elemental iron for:

• Iron deficiency anemia
• Iron deficiency

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Syracuse University

Collaborator

Trials

54

Recruited

118,000+

University of Ghana

Collaborator

Trials

48

Recruited

119,000+

National Blood Service Ghana

Collaborator

Trials

4

Recruited

1,800+

Liverpool School of Tropical Medicine

Collaborator

Trials

96

Recruited

804,000+

National Blood Service Ghana

Collaborator

Trials

4

Recruited

1,800+

Published Research Related to This Trial

Iron supplementation (75 mg per day as ferrous gluconate) significantly improved iron status and hemoglobin levels in female blood donors with low hematocrit levels, as shown by increased serum ferritin and iron values by the second follow-up visit.

Despite the improvements in iron status and hemoglobin, there was no significant difference in the overall suitability to donate blood between the iron and placebo groups, indicating that while iron supplementation is beneficial for iron levels, it does not affect the ability to donate blood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron supplementation in female blood donors deferred by copper sulfate screening. Cable, RG., Morse, EE., Keltonic, J., et al.[2019]

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]

A large survey of 53,989 blood donors revealed that only 21.4% reported using iron supplements, primarily in the form of multivitamins, indicating a significant gap in iron supplementation practices among donors.

The study found that iron supplement use was more common among older donors and those who donated blood more frequently, suggesting that targeted communication about the importance of iron for blood donation is necessary to improve supplement uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron supplementation by blood donors: demographics, patterns of use, and motivation. Cable, RG., Spencer, BR.[2020]

In a study involving 543 participants, the wax-matrix tablet of ferrous sulfate was associated with significantly fewer adverse effects compared to conventional ferrous sulfate tablets.

Eighty-one percent of participants using the wax-matrix preparation reported no severe or moderate side effects, while only 50% of those taking the conventional tablets had the same experience, indicating better tolerability of the wax-matrix formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of iron supplementation: a comparative trial of a wax-matrix iron preparation and conventional ferrous sulfate tablets. Brock, C., Curry, H., Hanna, C., et al.[2014]

In a double-blind study of 627 blood donors, daily supplementation with 66.6 mg of ferrous fumarate for 45 days was found to be the minimal effective dose for maintaining iron reserves, especially important for frequent donors.

The iron supplement was generally well tolerated, with only a slight increase in gastrointestinal upset compared to the placebo group, indicating its safety for use in blood donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A laboratory report on iron supplementation in blood donors. I. Tobias, KI., Camp, FR., Linville, A., et al.[2019]

After donating blood, repeat donors experienced a significant drop in ferritin levels, averaging a 55% decrease after 56 days, indicating a notable loss of iron stores.

Hepcidin levels showed the most significant changes post-donation and varied greatly among individuals, suggesting that measuring hepcidin and its ratio to ferritin could help predict how well donors recover their iron levels and support erythropoiesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepcidin/Ferritin Quotient Helps to Predict Spontaneous Recovery from Iron Loss following Blood Donation. Lotfi, R., Kroll, C., Plonné, D., et al.[2020]

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]

Citations

1. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00167-X/fulltext

Ferritin-guided iron supplementation as an alternative or ... Iron supplementation is an effective alternative or supplement to extended donation intervals for whole-blood donors with low ferritin levels.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7393577/

The benefits of iron supplementation following blood donation ... Iron supplements markedly enhance recovery from whole blood donation in donors with ferritin <50 ng/mL. However, full recovery from donation requires over 100 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5094173/

Oral Iron Supplementation After Blood Donation Our findings support studies showing that iron supplementation reduces the high rate of low-hemoglobin donor deferrals, currently 17.7% among ...

4. medrxiv.org medrxiv.org/content/10.1101/2025.01.03.25319940v1

Ferritin-guided iron supplementation in whole blood ... 60 mg iron supplements taken daily was shown to be the most effective strategy for mitigating ID, low Hb, and especially low ferritin without introducing ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1290/503144/Impact-of-Iron-Supplementation-in-Anemic-Voluntary

Impact of Iron Supplementation in Anemic Voluntary First-Time ... This study tested the hypothesis that low-dose iron supplementation will increase hemoglobin levels sufficiently among anemic individuals to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9749410/

Iron Deficiency and Blood Donation: Links, Risks and ... The AABB bulletin #17-02 correctly advocates low-dose iron supplements (≥18 mg/day for 60 days after WB donation or after every fourth or fifth ...

7. professionaleducation.blood.ca professionaleducation.blood.ca/en/transfusion/publications/importance-iron-whole-blood-donors-canadian-perspective

The importance of iron for whole blood donors: a Canadian ... A daily supplement (37.5 mg of elemental iron) for 8 weeks should be sufficient to replenish iron losses from a whole blood donation.