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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an iron injection (Injectafer) can improve oxygen levels and exercise performance in people at high altitudes. Researchers aim to determine if iron can ease breathing and exercise when oxygen levels are lower, similar to conditions on a mountain. The trial compares the effects of iron with a placebo (a harmless, inactive substance) to assess any real benefit. Individuals who exercise regularly and can run two miles in 21 minutes or less might be suitable participants. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Injectafer?

Studies have shown that Injectafer, the intravenous iron treatment in this trial, is generally safe and well-tolerated. Past research found side effects in about 1% of patients, with most being mild and similar to those of other iron treatments. Common issues included temporary reactions at the injection site and mild headaches. Importantly, Injectafer has U.S. approval for treating iron deficiency, supporting its safety. For any concerns, discussing them with the trial team or a doctor may be helpful. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Injectafer is unique because it directly addresses hypoxia by delivering iron intravenously, which can enhance oxygen transport in the body. Unlike traditional oral iron supplements that often take longer to work and can cause gastrointestinal side effects, Injectafer offers a fast-acting alternative with fewer digestive issues. Researchers are excited about this treatment because it has the potential to rapidly improve oxygen levels, providing a new option for patients who need quick relief from hypoxia.

What evidence suggests that intravenous iron might be an effective treatment for hypoxia?

This trial will compare the effects of intravenous iron, specifically Injectafer, with a placebo in participants. Research has shown that Injectafer, administered through an IV, can improve symptoms and exercise capacity in individuals with heart failure. Heart failure often correlates with low oxygen levels, suggesting that Injectafer might also enhance oxygen levels and exercise performance in low-oxygen conditions, such as high altitudes. Studies have found that iron is crucial for enabling blood to carry oxygen, essential for both rest and activity. Additionally, receiving iron through an IV has proven safe and effective for treating iron deficiency without causing serious side effects. This evidence supports the potential of Injectafer to improve oxygen levels and exercise ability, even in challenging conditions. ^{2 3 6 7 8}

Who Is on the Research Team?

Roy Salgado, PhD

Principal Investigator

United States Army Research Institute of Environmental Medicine

Are You a Good Fit for This Trial?

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

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

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

BMI 18.5-30 kg/m2

Exclusion Criteria

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

I have a history of inflammatory bowel disease.

Present condition of alcoholism, use of anabolic steroids, other substance abuse issues

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6142502/

Single-dose intravenous iron for iron deficiency: a new ... The authors concluded that both preparations are effective and safe without risk of serious adverse events. A similar conclusion was reached in a comparison of ...

2. withpower.com withpower.com/trial/phase-4-hypoxia-3-2022-43564

Intravenous Iron for 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0887796325000306

Intravenous Iron Therapy Versus Blood Transfusion for ... Our findings indicate that blood transfusion is more effective in achieving a rapid increase in hemoglobin levels shortly after therapy initiation.

4. academic.oup.com academic.oup.com/ckj/article/14/4/1067/6006724

Intravenous iron therapy and the cardiovascular system: risks ... In this review we discuss the risks of functional iron deficiency and the possible benefits and risks of iron therapy for the cardiovascular system.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2304968

Ferric Carboxymaltose in Heart Failure with Iron Deficiency The IRONOUT HF trial showed that oral iron therapy did not improve exercise capacity in patients who had heart failure with a reduced ejection fraction and iron ...

6. injectaferhcp.com injectaferhcp.com/safety-and-efficacy/safety-profile

Safety Profile | INJECTAFER® (ferric carboxymaltose injection) Adverse reactions reported in ≥1% of patients in adult pivotal trials 1 and 21. Term, Injectafer (N=1775) %, Pooled comparators* (N=1783) %, Oral iron

7. daiichisankyo.us daiichisankyo.us/press-releases/-/article/injectafer-approved-in-the-u-s-for-the-treatment-of-iron-deficiency-in-adult-patients-with-heart-failure

INJECTAFER® Approved in the U.S. for the Treatment ... The safety results from the trial were generally consistent with the known safety profile of INJECTAFER. The most common treatment emergent ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01265108

Effects of Iron on Exercise Capacity During Hypoxia | ... Intravenous iron supplementation has recently been shown to reverse pulmonary hypertension in healthy humans at high altitude, and to prevent pulmonary ...