Iron Supplements for Iron Deficiency in Pregnancy

(EASE-Iron Trial)

Recruiting at 1 trial location

Overseen By Lulu Pei, MSc

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Proton pump inhibitors, antibiotics

Disqualifiers: Sickle cell, Celiac, Smoking, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

172 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two iron supplements, ferrous fumarate and ferrous bisglycinate, affect iron levels and gut health in pregnant individuals. The goal is to determine which supplement better prevents and treats iron deficiency in both mothers and babies. It targets generally healthy, low-risk pregnant individuals living around Vancouver, who are between 13 and 25 weeks into their pregnancy and willing to provide blood and stool samples. As an unphased trial, participants contribute to valuable research that may enhance prenatal care.

Will I have to stop taking my current medications?

The trial requires that you do not use medications known to interfere with iron metabolism or gut health, such as proton pump inhibitors, anti-inflammatory agents, non-steroidal anti-inflammatory drugs, and antibiotics.

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

Research shows that both ferrous bisglycinate and ferrous fumarate are generally safe during pregnancy.

Studies suggest that ferrous bisglycinate is safe for pregnant individuals. This type of iron is gentle on the stomach and less likely to cause harm or unpleasant side effects compared to other iron types.

Ferrous fumarate is often used to prevent iron deficiency during pregnancy. Some individuals may experience mild side effects like stomach pain or nausea, but these are usually not severe.

Overall, current evidence considers both types of iron supplements safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ferrous bisglycinate for treating iron deficiency in pregnancy because it offers a potentially more efficient and gentle option compared to traditional iron supplements like ferrous fumarate. Unlike ferrous fumarate, which can cause gastrointestinal side effects, ferrous bisglycinate is believed to be better tolerated, with fewer digestive issues. Additionally, both ferrous bisglycinate and ferrous fumarate deliver the same amount of elemental iron, but bisglycinate's unique structure might result in improved absorption, making it an attractive alternative for ensuring pregnant individuals get the iron they need.

What evidence suggests that this trial's treatments could be effective for iron deficiency in pregnancy?

This trial will compare ferrous bisglycinate and ferrous fumarate for treating iron deficiency in pregnancy. Research has shown that ferrous bisglycinate, which participants in this trial may receive, effectively prevents iron deficiency anemia in pregnant women. Studies suggest it might work better and cause fewer side effects than other iron supplements. More than 98% of pregnant women taking ferrous bisglycinate reported it was easy to tolerate, with many experiencing improved hemoglobin levels.

In contrast, studies have confirmed that ferrous fumarate, another treatment option in this trial, effectively treats iron deficiency anemia during pregnancy. It is a commonly used and safe option to boost iron levels and improve health for both mother and baby. Both treatments are good choices for maintaining healthy iron levels during pregnancy. ^{1 2 6 7 8}

Who Is on the Research Team?

Crystal Karakochuk, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for healthy pregnant individuals aged 19-42 in Vancouver, expecting one baby and planning to deliver at BC Women's Hospital. They should be 13-25 weeks into their pregnancy and able to visit the University of British Columbia. Exclusions include a BMI ≥30, smoking recently, certain pre-existing conditions affecting iron levels, or use of specific medications.

Inclusion Criteria

You are in your second trimester of pregnancy, between 13 and 25 weeks.

I am pregnant, between 19 and 42 years old, and expecting one baby.

I plan to give birth at BC Women's Hospital.

Exclusion Criteria

You have a history of neural tube defects or have had a previous pregnancy with a neural tube defect.

I have a health condition that affects my body's iron levels.

I am currently receiving blood transfusions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline visit includes informed consent, randomization, provision of study supplements, and collection of baseline data

1 day

1 visit (in-person)

Treatment

Participants receive daily iron and prenatal multivitamin supplements from baseline to delivery, with monthly follow-up surveys

12 weeks

Monthly virtual follow-ups

Follow-up

Follow-up visit includes collection of remaining supplements, weight measurement, blood draw, and stool collection

2 weeks

1 visit (in-person)

Optional Continuation

Participants who plan to breastfeed may continue supplementation and provide breastmilk samples postpartum

4 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Ferrous bisglycinate
• Ferrous fumarate

Trial Overview The study tests two types of iron supplements: Ferrous fumarate and Ferrous bisglycinate taken with prenatal vitamins during pregnancy until delivery. The goal is to compare how each supplement affects body iron stores and gut bacteria presence by analyzing blood samples and rectal swabs from start till around week 37.

How Is the Trial Designed?

Group I: Ferrous bisglycinate Experimental Treatment 1 Intervention

24 mg elemental iron/day

Group II: Ferrous fumarate Active Control 1 Intervention

24 mg elemental iron/day

Ferrous bisglycinate is already approved in Canada, European Union, United States for the following indications:

Approved in Canada as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Approved in European Union as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Approved in United States as Ferrous bisglycinate for:

• Prevention and treatment of iron deficiency in pregnancy

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Iron amino acid chelates, particularly ferrous bis-glycine chelate (FeBC), are effective in treating iron deficiency anemia and are better absorbed from various food sources compared to traditional ferrous sulfate.

Despite their efficacy, the use of FeBC in national fortification programs is limited by cost and potential changes in food taste, highlighting the need for further research on its bioavailability and comparison with other iron supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron amino acid chelates. Hertrampf, E., Olivares, M.[2013]

In a study of 80 pregnant women, ferrous bisglycinate (25 mg iron/day) was found to be as effective as ferrous sulfate (50 mg iron/day) in preventing iron deficiency and iron deficiency anemia during pregnancy.

Ferrous bisglycinate resulted in fewer gastrointestinal complaints compared to ferrous sulfate, making it a potentially safer option for iron supplementation in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. Milman, N., Jønsson, L., Dyre, P., et al.[2019]

Ferrous bisglycinate chelate (Ferrochel) is a highly stable and bioavailable form of iron that causes fewer side effects compared to traditional iron salts, making it a safer option for iron supplementation.

In a study with Sprague-Dawley rats, no adverse effects were observed at doses up to 500 mg/kg body weight/day, establishing this as the no-observed-adverse-effect level (NOAEL) for this compound.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of ferrous bisglycinate chelate. Jeppsen, RB., Borzelleca, JF.[2019]

In a study involving 100 pregnant women with iron deficiency anemia, both bovine lactoferrin and ferrous sulfate effectively increased hemoglobin and iron levels after 30 days of treatment, showing similar efficacy.

Bovine lactoferrin was associated with significantly fewer gastrointestinal side effects, such as abdominal pain and constipation, compared to ferrous sulfate, making it a potentially safer option for treating iron deficiency in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. Nappi, C., Tommaselli, GA., Morra, I., et al.[2014]

In a study of 187 pregnant women with iron deficiency anemia, those treated with ferrous bis-glycinate experienced a significantly greater increase in hemoglobin levels (2.48 g/dL) compared to those receiving ferrous glycine sulfate (1.32 g/dL) after 8 weeks.

Ferrous bis-glycinate not only proved to be more effective, with 89.2% of women reaching hemoglobin levels above 11 g/dL, but also had a better safety profile, as the rate of adverse effects was significantly higher in the ferrous glycine sulfate group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. Abbas, AM., Abdelbadee, SA., Alanwar, A., et al.[2020]

Ferrous bisglycinate supplementation for 4-20 weeks significantly increased hemoglobin concentrations in pregnant women compared to other iron supplements, with a standardized mean difference of 0.54 g/dL.

This novel iron supplement was also associated with fewer gastrointestinal adverse events, showing an incidence rate ratio of 0.36, indicating it may be a safer option for those at risk of iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials. Fischer, JAJ., Cherian, AM., Bone, JN., et al.[2023]

In a study of 120 pregnant women with iron deficiency, supplementation with ferrous bisglycinate plus folinic acid showed significantly better iron absorption and hematological improvements compared to ferrous fumarate, despite a lower iron dosage.

The ferrous bisglycinate group reported fewer side effects, such as nausea and abdominal pain, indicating it may be a more tolerable option for managing iron deficiency during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial. Bumrungpert, A., Pavadhgul, P., Piromsawasdi, T., et al.[2023]

In a study of 150 pregnant women with iron deficiency anemia, both iron amino acid chelate (IAAC) and ferrous fumarate (FF) were effective in treating the condition over 12 weeks, but IAAC led to a significantly faster increase in hemoglobin levels.

IAAC was better tolerated than FF, with fewer reported side effects such as constipation and abdominal pain, making it a preferable option for treating iron deficiency anemia during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acid chelated iron versus an iron salt in the treatment of iron deficiency anemia with pregnancy: A randomized controlled study. Abdel Moety, GAF., Ali, AM., Fouad, R., et al.[2018]

In a study involving 145 pregnant women, daily supplementation with 15 mg of iron from iron-bis-glycinate chelate (Ferrochel) was found to be significantly more effective than 40 mg of iron from ferrous sulfate in preventing iron deficiency, despite the lower dosage.

Only 30.8% of women taking Ferrochel experienced iron depletion compared to 54.5% of those taking ferrous sulfate, and taste issues led to non-compliance in 29.8% of the ferrous sulfate group, highlighting Ferrochel's better tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women. Szarfarc, SC., de Cassana, LM., Fujimori, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8839493/

Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in ... Ferrous bisglycinate has also proven clinically effective for preventing iron deficiency anemia (IDA) in infants [6]. This comparative study ...

2. balchem.com balchem.com/news/iron-bisglycinate-pregnancy-study/

Meta-Analysis prods Ferrochel® Clinical Trials that ... Meta-Analysis Confirms Ferrous Bisglycinate has Greater Efficacy and Lower Risk of Side Effects Compared to Other Iron Salts in Pregnant Women.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10331582/

The effects of oral ferrous bisglycinate supplementation on ... Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women.

4. ijrcog.org ijrcog.org/index.php/ijrcog/article/view/13010

Real-world evaluation of safety and effectiveness of ferrous ... Furthermore, 93% of pregnant women rated the tolerability as very good to good, and >98% of patients complied with >80% of treatment with ...

5. researchgate.net researchgate.net/publication/11665308_Relative_effectiveness_of_iron_bis-glycinate_chelate_Ferrochel_and_ferrous_sulfate_in_the_control_of_iron_deficiency_in_pregnant_women

(PDF) Relative effectiveness of iron bis-glycinate chelate ... Iron depletion was found in 30.8% of the women treated with Ferrochel and in 54.5% of the women than consumed ferrous sulfate. Of the factors ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9669178/

The Incidence, Complications and Treatment of Iron ... Multiple clinical trials have found FCM to be safe in the second and third trimester of pregnancy. A prospective observational study analyzed data from 863 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278691599000526

Safety Evaluation of Ferrous Bisglycinate Chelate It is well tolerated and its toxicity is less than that of inorganic iron salts. The safety of ferrochel has been well established in its use for food ...

8. who.int who.int/data/nutrition/nlis/info/antenatal-iron-supplementation

Antenatal iron supplementation Daily iron and folic acid supplementation is currently recommended by WHO as part of antenatal care, to reduce the risk of low birth weight, maternal anaemia ...