Effects of Iron on Exercise Capacity During Hypoxia

Study Overview
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Brief Summary
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During alveolar hypoxia, for example at high altitude or in patients with respiratory disease, there is evidence to suggest that hypoxia-induced pulmonary hypertension might limit exercise performance. Intravenous iron supplementation has recently been shown to reverse pulmonary hypertension in healthy humans at high altitude, and to prevent pulmonary hypertension in volunteers exposed to hypoxia at sea level. The investigators hypothesized that intravenous iron supplementation would enhance exercise capacity during alveolar hypoxia.

Official Title
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Effects of Intravenous Iron Supplementation on Exercise Capacity During Sustained Alveolar Hypoxia in Healthy Humans.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Iron sucrose.
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 60 years Sea level natives with no recent exposure to high altitude Baseline iron indices within the normal range Detectable tricuspid regurgitation on echocardiography Exclusion Criteria: Significant cardiorespiratory disease Known susceptibility to high altitude-related illness Taking medications or iron supplementation Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron sucrose<br>Infusion of 200 mg iron sucrose (Venofer) in 100 ml normal (0.9%) saline. | Drug: Iron sucrose.<br>* Volunteers will receive an intravenous infusion of 200 mg iron sucrose, before exposure to 8 hours of alveolar hypoxia. At the end of the exposure, pulmonary artery systolic pressure will be measured and volunteers will undertake an exercise test while breathing hypoxic gas.<br>* Other names: Iron sucrose = Venofer;|
| Placebo Comparator: Intravenous normal saline<br>Infusion of 100 ml normal (0.9%) saline. | Drug: Normal saline<br>* Volunteers will receive an intravenous infusion of 100 ml normal saline, before exposure to 8 hours of alveolar hypoxia. At the end of the exposure, pulmonary artery systolic pressure will be measured and volunteers will undertake an exercise test while breathing hypoxic gas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal exercise capacity during hypoxia, assessed by maximal oxygen consumption. | Volunteers will receive either intravenous iron or saline placebo, before exposure to 8 hours of alveolar hypoxia. They will then undergo an exercise test while breathing an hypoxic gas mixture. The primary outcome measure will be exercise capacity as determined by maximal oxygen consumption during this test. Volunteers will receive both interventions, via a crossover design. Due to uncertainty about the duration of action of iron at a cellular level, all volunteers will receive saline infusion on the first study day, and iron sucrose infusion on a second study day, at least one week later. | After 8-h exposure to alveolar hypoxia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal exercise capacity, assessed by peak power output. |  | After 8-h exposure to alveolar hypoxia. | 
| Pulmonary artery systolic pressure. |  | After 8-h exposure to alveolar hypoxia. | 
| Blood levels of oxygen-regulated proteins. |  | After 8-h exposure to alveolar hypoxia |