Iron Supplementation for Scoliosis

(KIDS Trial)

Overseen By Lisa Eisler, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Must not be taking: Iron supplements

Disqualifiers: Iron disorder, Pregnancy, Prisoners, others

Compensation: Varies

Number of Visits: Unknown

275 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take iron supplements on your own or as prescribed by a doctor during the study.

Is iron supplementation generally safe for humans?

Iron supplements like ferrous sulfate are generally safe for humans, but they can cause side effects like stomach upset and, in rare cases, more serious issues like mucosal injury in the digestive tract. Some studies found that newer formulations may have fewer side effects compared to traditional ferrous sulfate tablets. ^{1 2 3 4 5}

How does the drug ferrous sulfate differ from other treatments for scoliosis?

Ferrous sulfate is unique for scoliosis treatment as it involves oral iron supplementation, which is not a standard approach for this condition. Unlike typical scoliosis treatments that focus on physical therapy or surgery, this trial explores the potential role of iron in managing scoliosis, which is novel and not commonly practiced. ^{1 2 6 7 8}

What is the purpose of this trial?

This study is a randomized controlled trial of preoperative oral iron supplementation, to identify whether iron deficiency is a modifiable risk factor for adverse surgical outcomes such as red blood cell transfusion and diminished postoperative cognitive and physical capacity in adolescents undergoing scoliosis surgery. Research Question(s)/Hypothesis(es): Primary * Iron supplementation will reduce the incidence of perioperative RBC transfusion in iron deficient scoliosis patients undergoing spinal fusion. Secondary * Iron supplementation will reduce postoperative neurocognitive functional declines in iron deficient scoliosis patients undergoing spinal fusion. * Iron supplementation will improve patient-reported physical functioning in iron deficient scoliosis patients undergoing spinal fusion.

Research Team

Lisa D Eisler, MD

Principal Investigator

Columbia University

Eligibility Criteria

Adolescents aged 12-19 with scoliosis and iron deficiency (serum ferritin ≤25 µg/L) who can swallow tablets and are scheduled for spinal fusion surgery at least 13 weeks away. Excluded are those with a history of iron overload, high inflammation markers, allergies to iron supplements, current use of iron supplements they won't stop, nutritional support recipients, transfusion objectors, pregnant individuals or prisoners.

Inclusion Criteria

I can swallow pills.

Your blood ferritin level is less than or equal to 25 micrograms per liter.

I am between 12 and 19 years old.

Exclusion Criteria

I refuse to receive red blood cell transfusions.

Current pregnancy (by self-report)

Currently getting special food or drinks for nutrition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Treatment

Participants receive daily oral iron or placebo tablets for 3-6 months prior to surgery

3-6 months

Surgery and Immediate Postoperative

Participants undergo spinal fusion surgery and are monitored for perioperative RBC transfusion

4 to 30 days

Follow-up

Participants are monitored for postoperative neurocognitive and physical capacity declines

3-6 months

Treatment Details

Interventions

• Oral ferrous sulfate
• Oral placebo tablet

Trial Overview The trial is testing if taking oral ferrous sulfate (iron) before surgery can reduce the need for blood transfusions during operation and improve cognitive and physical recovery after scoliosis surgery in adolescents. Participants will be randomly given either the iron supplement or a placebo tablet.

Participant Groups

Group I: Oral ferrous sulfate Experimental Treatment 1 Intervention

Participants will receive oral ferrous sulfate tablets, 325mg (65mg elemental iron). Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.

Group II: Observational follow-up Active Control 1 Intervention

Participants who do not qualify for randomization may be invited to complete study measures through postoperative follow-up as part of an observational study.

Group III: Oral placebo tablets Placebo Group 1 Intervention

Participants will receive placebo tablets. Tablets are to be taken once daily for 3-6 months prior to surgery as time allows.

Oral ferrous sulfate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ferrous sulfate for:

• Iron deficiency anemia
• Preoperative iron supplementation for surgical procedures

Approved in European Union as Ferrous sulphate for:

• Iron deficiency anemia
• Preoperative iron supplementation for surgical procedures

Approved in Canada as Ferrous sulfate for:

• Iron deficiency anemia
• Preoperative iron supplementation for surgical procedures

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Findings from Research

Ferrous sulfate, a common treatment for iron deficiency anemia, can cause mucosal damage in the upper gastrointestinal tract, leading to a condition known as 'iron-pill gastritis'.

This report highlights a rare case of 'iron pill-induced duodenitis', where a female patient in her 50s exhibited unusual duodenal iron deposition and mucosal injury, indicating that oral iron supplements can also affect the duodenum, not just the stomach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass. Jeung, J., Ashour, S., Fuller, L.[2021]

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 involving 60 premenopausal women, the novel iron multi-amino acid chelate (IMAAC) preparation was found to be better tolerated than ferrous sulfate, with significantly fewer reported adverse effects.

The study showed no significant differences in hematological outcomes between IMAAC, ferrous sulfate, and placebo, indicating that while IMAAC is safer, it does not compromise iron efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind clinical study on the safety and tolerability of an iron multi-amino acid chelate preparation in premenopausal women. Fouad, GT., Evans, M., Sharma, P., et al.[2014]

In a 12-week study involving 72 participants with uncomplicated iron deficiency anemia, a ferrous iron supplement (Ferall) was found to be significantly more effective than a ferric iron polysaccharide complex (Niferex) in improving hemoglobin and serum ferritin levels.

While the ferrous product was associated with a slightly higher frequency of gastrointestinal side effects, both supplements were well tolerated, and no participants withdrew due to side effects, indicating that the ferrous product is safe and effective for treating iron deficiency anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. Liu, TC., Lin, SF., Chang, CS., et al.[2019]

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 study of 138 anemic schoolchildren in Brazil, both ferrous sulfate and iron bis-glycinate chelate supplementation significantly increased hemoglobin levels after 8 weeks, with ferrous sulfate showing a 1.1 g/dL increase and iron bis-glycinate chelate a 0.9 g/dL increase.

Children with low initial serum ferritin levels experienced increased ferritin concentrations after supplementation, confirming that both iron interventions are effective for addressing iron deficiency and anemia, although no significant differences were found between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of different iron supplementation strategies on hemoglobin and ferritin levels among schoolchildren in Teresina, Piauí State, Brazil]. Dos Santos, MM., Nogueira, Ndo N., Diniz, Ada S.[2019]

The gastric delivery system (GDS) for iron supplementation showed three times higher iron absorption compared to conventional ferrous sulphate in a study with 9 volunteers.

In a double-blind trial with 200 women, GDS caused significantly fewer gastrointestinal side effects, such as nausea and anorexia, compared to ferrous sulphate, making it a safer alternative for iron supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric delivery system for iron supplementation. Cook, JD., Carriaga, M., Kahn, SG., et al.[2019]

In a study involving 10 healthy male volunteers, enteric-coated ferrous sulfate preparations showed significantly lower bioavailability of iron, with area under the curve (AUC) values less than 30% compared to an oral solution.

In contrast, the two film-coated tablet preparations had AUCs that were essentially equivalent to the oral solution, indicating they are more effective for iron absorption and should be preferred over enteric-coated options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of iron in oral ferrous sulfate preparations in healthy volunteers. Walker, SE., Paton, TW., Cowan, DH., et al.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass. [2021]

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. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind clinical study on the safety and tolerability of an iron multi-amino acid chelate preparation in premenopausal women. [2014]

4. Japan pubmed.ncbi.nlm.nih.gov

Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. [2019]

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

Adverse effects of iron supplementation: a comparative trial of a wax-matrix iron preparation and conventional ferrous sulfate tablets. [2014]

6. Brazil pubmed.ncbi.nlm.nih.gov

[Effectiveness of different iron supplementation strategies on hemoglobin and ferritin levels among schoolchildren in Teresina, Piauí State, Brazil]. [2019]

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

Gastric delivery system for iron supplementation. [2019]

8. Canada pubmed.ncbi.nlm.nih.gov

Bioavailability of iron in oral ferrous sulfate preparations in healthy volunteers. [2018]