Intravenous Iron Effects on Performance at High Altitude

Intravenous Iron Prophylaxis for Rapid High Altitude Insertions

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

Study Overview

• Status: Recruiting
• Conditions: Hypoxia
• Intervention / Treatment: Other: Placebo; Drug: Injectafer

Detailed Description

This study will use a double-blind randomized study design in which one group will receive iron (n = 12; Injectafer, 15 mg/kg up to 1000 mg) and the other a placebo (n = 12; saline). Twenty-four participants will complete seven study visits: Visit 1: Orientation visit consisting of dual-energy X-ray absorptiometry scan (DEXA), pulmonary function test, assessment of peak aerobic capacity (VO2peak); Visits 2-3: familiarization consisting of exercise battery (20 minutes of walking followed by 2 mile treadmill time trial); Visits 4, 6-7: high altitude trial (4,800 m) in which skin blood flow during rest will be measured, ventilation at sea level and altitude will be assessed, collection of sea level and altitude arterialized capillary and venous blood will be collected, and the exercise battery. Visit 5: participants will receive the iron or placebo.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Roy Salgado, PhD; Phone Number: 508-206-2375; Email: roy.m.salgado.civ@health.mil

Study Locations

• United States
  • Massachusetts
    • Natick, Massachusetts, United States, 01760
      • Recruiting
      • USARIEM
      • Contact: Roy M Salgado, Ph.D.; Phone Number: 508-206-2375; Email: roy.m.salgado.civ@mail.mil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Man or woman, age 18-40 years

  • BMI 18.5-30 kg/m2
  • In good health as determined by the Office of Medical Support & Oversight (OMSO) General Medical Clearance
  • Passed his/her most recent Army Combat Fitness Test (ACFT) (Military Volunteers Only) or exercises at least 2 times per week and able to complete two mile run in ≤ 21 minutes (Civilian Volunteers)
  • Willing to not exercise, or drink alcoholic/caffeinated beverages 24 hours prior to each testing session
  • Willing to not perform any strenuous exercise 36 hours prior to each testing session

Exclusion Criteria:

• Women who are pregnant or planning to become pregnant during the study

  • Taking prescription medication, or over-the-counter medications other than contraceptives, unless approved by OMSO & PI
  • Taking dietary supplements unless approved by OMSO & PI
  • Born at altitudes greater than 2,100 m (7,000 ft)
  • Living in areas that are more than 1,200 m (4,000 ft) or have traveled to areas that are more than 1,200 m for five days or more within the last 2 months
  • Prior diagnosis of High Altitude Pulmonary Edema (HAPE) or High Altitude Cerebral Edema (HACE)
  • Musculoskeletal injuries that compromise the ability to walk/run on a treadmill
  • Presence of abnormal blood chemicals (hemoglobin S or Sickle Cell Trait)
  • Hemoglobin concentration: men: Hb <13.5 g/dL or Hb >17.7 g/dL; women Hb <12.5 g/dL or Hb >15.9 g/dL
  • Ferritin < 50 ng/mL or greater than 150 ng/mL
  • Any history of malignancy
  • Personal or family history of blood clots
  • History of thromboembolic disease, hypertension, and known risk factors of cardiovascular disease
  • Blood donation within 8 weeks of beginning the study
  • History of seizures
  • History of inflammatory bowel disease
  • Any recent (within 4-6 weeks) and or expected history of prolonged periods of immobility or limited activity (including recent or upcoming surgery)
  • Abnormal PT/PTT test or problems with blood clotting
  • Any nicotine or recreational drug use (unless quit > 1 month prior to study orientation)
  • Presence of respiratory tract infections (< 1 month prior)
  • Experience recent cold, coughs, or sinus infections (< 2 weeks prior)
  • Allergy to skin adhesive
  • Evidence of apnea or sleeping disorder
  • Present condition of alcoholism, use of anabolic steroids, other substance abuse issues
  • Body mass <50 kg (110.5 lbs)
  • History of hyperparathyroidism
  • History of vitamin D deficiency
  • History of systemic inflammatory disease (rheumatoid arthritis, lupus erythematosus)
  • Any drug allergies
  • History of hypersensitivity reaction
  • History of asthma
  • History of kidney or liver disease
  • Any previous intravenous iron injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo; Placebo - saline	Other: Placebo; Placebo
Experimental: Intravenous iron; Iron - Injectafer 15 mg/kg up to 1000 mg	Drug: Injectafer; Injectafer - 15 mg/kg up to 1000 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 mile treadmill time trial performance	Time to complete self-paced 2 miles treadmill time trial (min:sec)	Baseline at sea level, pre intervention at altitude, one week post intervention at altitude, and two weeks post intervention at altitude.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation rate	Ventilation rate will be assessed using a pneumotachometer (l/min).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Percent body fat	Percent body fat will be assessed using Dual Energy X-ray Absorptiometry (%body fat).	Will be assessed once at the beginning of the study.
Oxygen Saturation	Oxygen saturation will be assessed using a finger pulse oximeter (%).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Hematocrit	Hematocrit will be assessed using manual hematocrit method (%).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Ferritin	Ferritin will be assessed using an ELISA (ng/ml).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
C-reactive protein	C-reactive protein will be assessed using an ELISA (mg/L).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Soluble transferrin	Soluble transferrin will be assessed using an ELISA (mg/L).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Arterialized capillary PO2	Arterialized capillary PO2 will be assessed using a blood gas analyzer (mmHg).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Arterialized capillary PCO2	Arterialized capillary PCO2 will be assessed using a blood gas analyzer (mmHg).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Arterialized capillary pH	Arterialized capillary pH will be assessed using a blood gas analyzer.	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
Skin Blood flow	Skin blood flow will be assessed via laser doppler (arbitrary units).	Pre intervention at sea level and altitude, one week post intervention at sea level and altitude, and two weeks post intervention at sea level and altitude.
VO2peak	Peak aerobic capacity will be assessed using a metabolic cart (ml/kg/min and or l/min).	Will be assessed once on day 1.
Pulmonary function test	Pulmonary function test will be performed to determine forced vital capacity (FVC; L) using a metabolic cart.	Will be assessed once on day 1.
Pulmonary function test	Pulmonary function test will be performed to determine forced expired volume in one second (FEV1; L) using a metabolic cart.	Will be measured once on day 1.

Collaborators and Investigators

• Sponsor: United States Army Research Institute of Environmental Medicine
• Investigators: Principal Investigator: Roy Salgado, PhD, United States Army Research Institute of Environmental Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: October 31, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Actual): November 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: 21-24HC (M-10949); 000000 (MRDC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes