Intravenous Iron for Hypoxia

Overseen By Roy Salgado, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: United States Army Research Institute of Environmental Medicine

Must not be taking: Prescription medications

Disqualifiers: Pregnancy, High altitude, Cardiovascular, 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: 11

Duration: 1 day

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking prescription or over-the-counter medications, unless they are approved by the study's medical team. You should discuss your current medications with them to see if you can continue taking them during the trial.

What data supports the effectiveness of the drug Injectafer for treating hypoxia?

Injectafer, an intravenous iron treatment, has been shown to improve quality of life and exercise capacity in patients with heart failure, which is often associated with iron deficiency. This suggests that it may help improve oxygen levels in the body, potentially benefiting conditions like hypoxia. ^{1 2 3 4 5}

How does the drug Injectafer differ from other treatments for hypoxia?

Injectafer, an intravenous iron treatment, is unique because it can reduce the increase in pulmonary artery pressure caused by hypoxia, and its effects last long after the iron is cleared from the blood. This makes it different from other treatments that may not have this prolonged effect on hypoxia-induced changes. ^{2 3 6 7 8}

What is the purpose of this trial?

To compare the effects of IV iron versus placebo (saline) injection on arterial oxygen saturation, submaximal exercise responses, and 2-mile treadmill time-trial performance during acute exposure to hypobaric hypoxia (430 mmHg, simulating \~4800m) assessed 1 and 14 days after treatment. Primary Hypothesis 1: IV iron treatment will improve arterial oxygen saturation at rest and during exercise in acute hypobaric hypoxia and this effect will persist for 2 weeks Primary Hypothesis 2) IV iron treatment will improve 2-mile treadmill time trial performance in acute hypobaric hypoxia and this effect will persist for 2 weeks

Research Team

Roy Salgado, PhD

Principal Investigator

United States Army Research Institute of Environmental Medicine

Eligibility Criteria

This trial is for people who are interested in how IV iron can affect oxygen levels and exercise performance when exposed to high altitude-like conditions. Participants should be healthy, without any medical issues that could interfere with the study.

Inclusion Criteria

Willing to not perform any strenuous exercise 36 hours prior to each testing session

In good health as determined by the Office of Medical Support & Oversight (OMSO) General Medical Clearance

BMI 18.5-30 kg/m2

Exclusion Criteria

I have a history of inflammatory bowel disease.

I have had cancer before.

Any nicotine or recreational drug use (unless quit > 1 month prior to study orientation)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Orientation and Baseline Assessment

Orientation visit including DEXA scan, pulmonary function test, and assessment of peak aerobic capacity (VO2peak)

1 day

1 visit (in-person)

Familiarization

Familiarization with exercise battery including 20 minutes of walking and 2-mile treadmill time trial

1 week

2 visits (in-person)

Treatment

Participants receive either IV iron or placebo (saline) injection

1 day

1 visit (in-person)

High Altitude Trial

High altitude trial at 4,800 m with measurements of skin blood flow, ventilation, and blood collection

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at sea level and altitude

2 weeks

3 visits (in-person)

Treatment Details

Interventions

• Injectafer

Trial Overview The trial tests whether an IV iron supplement (Injectafer) or a placebo (saline solution) can improve oxygen saturation and physical endurance during simulated high-altitude conditions, measured shortly after treatment and two weeks later.

Participant Groups

Group I: Placebo Experimental Treatment 1 Intervention

Placebo - saline

Group II: Intravenous iron Experimental Treatment 1 Intervention

Iron - Injectafer 15 mg/kg up to 1000 mg

Who Is Running the Clinical Trial?

United States Army Research Institute of Environmental Medicine

Lead Sponsor

Trials

67

Recruited

3,700+

Findings from Research

Intravenous ferric carboxymaltose (Injectafer®) is effective in improving quality of life and exercise capacity in patients with heart failure with reduced ejection fraction (HFrEF) and may reduce hospitalizations, making it a beneficial treatment for iron deficiency in this population.

Although anaphylactic reactions to Injectafer® are very rare, its administration is recommended in a medical setting, which can create challenges for both patients and healthcare providers in accessing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Why and how to treat iron deficiency in heart failure ?] Tridetti, J., Nguyen Trung, ML., Ancion, A., et al.[2020]

In a study of 172 patients with acute heart failure, those who received intravenous (IV) iron therapy showed a significant increase in hemoglobin levels compared to those who did not, with changes of 2.61 g/dl versus 0.23 g/dl by day 28.

The administration of IV iron was well tolerated, and while the 30-day readmission rates were 30% for the IV iron group and 22% for the control group, this difference was not statistically significant, suggesting that IV iron therapy does not increase readmission risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Total Dose Infusion of Iron Intravenously in Patients With Acute Heart Failure and Anemia (Hemoglobin Kaminsky, BM., Pogue, KT., Hanigan, S., et al.[2018]

In a study involving 143 non-hemodialysis adult outpatients, both intravenous iron dextran and iron sucrose had similar rates of immediate severe drug reactions, indicating comparable safety in that regard.

However, iron sucrose was associated with a significantly higher risk of delayed infusion reactions compared to iron dextran, suggesting that while both treatments are generally safe, iron dextran may be preferable for minimizing delayed side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study. Louzada, ML., Hsia, CC., Al-Ani, F., et al.[2020]

Intravenous (IV) iron therapy effectively and rapidly corrected severe nonhemorrhagic anemia in an 18-year-old pregnant woman, raising her hemoglobin from 4.8 g/dL to 8.1 g/dL, which is a significant improvement.

The treatment not only improved the mother's hemoglobin levels but also correlated with better fetal health outcomes, suggesting that high erythropoietin levels can indicate a positive response to IV iron, potentially reducing the need for blood transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron therapy for severe pregnancy anemia with high erythropoietin levels. Carretti, N., Paticchio, MR., Eremita, GA.[2019]

A reliable spectrophotometric method was developed to measure total iron and transferrin-bound iron (TBI) in human serum after intravenous iron-sucrose therapy, which is crucial for monitoring iron-deficiency anemia treatments.

This method allows for accurate differentiation of iron species, enabling better pharmacokinetic studies that can inform the development of effective iron therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of total and transferrin-bound iron in human serum for pharmacokinetic studies of iron-sucrose formulations. Goggin, MM., Gozum, SD., Burrows, DM., et al.[2018]

In a Phase 3 trial involving 230 anemic patients with chronic kidney disease on hemodialysis, intravenous ferumoxytol significantly increased hemoglobin levels more than oral iron, with an average increase of 1.02 g/dl compared to 0.46 g/dl for oral iron.

Ferumoxytol also resulted in a greater increase in transferrin saturation, and both treatments had similar rates of adverse events, indicating that ferumoxytol is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Provenzano, R., Schiller, B., Rao, M., et al.[2021]

In a study involving 22 participants, intravenous iron (ferric carboxymaltose) significantly reduced the rise in pulmonary artery systolic pressure (PASP) during sustained hypoxia by about 50%, and this effect persisted for at least 43 days after administration.

The study suggests that increasing iron stores can have a long-lasting impact on reducing hypoxia-induced pulmonary hypertension, indicating potential therapeutic benefits of intravenous iron in managing certain types of pulmonary hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia. Bart, NK., Curtis, MK., Cheng, HY., et al.[2019]

In an in vitro study using a closed-loop hemodialysis system, the novel intravenous iron formulation VIT 45 showed less than 0.5% removal during dialysis, indicating it is not significantly dialyzed by high-flux or high-efficiency membranes.

The study found that neither the type of dialysis membrane nor the ultrafiltration rate affected the removal of VIT 45, confirming that this iron formulation remains largely intact during hemodialysis procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of VIT 45 (IND#63,243 - American Regent) removal by closed loop in vitro hemodialysis system. Manley, HJ., McClaran, ML.[2019]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

[Why and how to treat iron deficiency in heart failure ?] [2020]

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

Effects of Total Dose Infusion of Iron Intravenously in Patients With Acute Heart Failure and Anemia (Hemoglobin [2018]

3. England pubmed.ncbi.nlm.nih.gov

Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study. [2020]

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

Intravenous iron therapy for severe pregnancy anemia with high erythropoietin levels. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Analysis of total and transferrin-bound iron in human serum for pharmacokinetic studies of iron-sucrose formulations. [2018]

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

Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. [2021]

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

Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia. [2019]

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

Determination of VIT 45 (IND#63,243 - American Regent) removal by closed loop in vitro hemodialysis system. [2019]