Study of the Effects of Iron Levels on the Lungs at High Altitude
Condition: Pulmonary Hypertension; Mountain Sickness
MeSH terms: Hypertension, Pulmonary; Altitude Sickness; Hypertension
Study type: Interventional

Summary: 
      The study hypothesis is that body iron levels are important in determining the increase in
      lung blood pressure that occurs in response to low oxygen levels. The purpose of this study
      is to determine whether this is true at high altitude, where oxygen levels are low.
    

Detailed description: 
      Pulmonary hypertensive disorders frequently complicate hypoxic lung disease and worsen
      patient survival. Hypoxia-induced pulmonary hypertension is also a major cause of morbidity
      at high altitude. Hypoxia causes pulmonary hypertension through hypoxic pulmonary
      vasoconstriction and vascular remodelling. These processes are thought to be regulated at
      least in part by the hypoxia-inducible factor (HIF) family of transcription factors, which
      coordinate intracellular responses to hypoxia throughout the body.

      HIF is regulated through a cellular degradation process that requires iron as an obligate
      cofactor. In cultured cells HIF degradation is inhibited by reduction in iron (by chelation
      with desferrioxamine) and potentiated by iron supplementation. In humans, we have recently
      shown that, in laboratory experiments lasting 8 hours, acute iron supplementation blunts the
      pulmonary vascular response to hypoxia, while acute iron chelation with desferrioxamine
      enhances the response.

      This suggests that iron may also affect the pulmonary artery pressure response to hypoxia
      over longer time periods. The purpose of this study is to investigate this link between iron
      and the pulmonary artery pressure response to hypoxia, through a study conducted at high
      altitude allowing concurrent exposure of larger numbers of participants to environmental
      hypoxia. We wish to explore the extent and the time-course of the effect of iron on pulmonary
      artery pressure. Cerro de Pascu (4,340 m) in Peru provides the unique ability to make rapid
      transitions from sea level to high altitude (6-8 hours by road), together with the requisite
      research facilities. Also, one part of this study involves recruitment of patients with
      chronic mountain sickness, of whom there are many living in Cerro de Pasco.
    

Intervention name(s): Iron sucrose; Normal saline; Venesection; Iron sucrose; Normal saline
Intervention type(s): Drug; Drug; Procedure; Drug; Drug
Intervention description(s): Single intravenous infusion of iron 200 mg; Single intravenous infusion of normal 0.9% saline 100 mls (as placebo); Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline.; Two intravenous infusions, each of 200 mg of iron, separated by one day.; Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.
Other intervention name(s): Venofer; Venofer
Intervention MeSH terms: Iron; Ferric Oxide, Saccharated
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Hypoxia; Iron; Hypoxia-Inducible Factor 1; Chronic mountain sickness