Study of the Effects of Iron Levels on the Lungs at High Altitude

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT00952302

Collaborator

Universidad Peruana Cayetano Heredia (Other)

Enrollment

Location

Arms

Duration (Months)

32.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension Mountain Sickness	Drug: Iron sucrose Drug: Normal saline Procedure: Venesection Drug: Iron sucrose Drug: Normal saline	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Physiology Study Investigating the Effects of Supplementation and Depletion of Iron on Hypoxia-related Pulmonary Hypertension

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Nov 1, 2008

Actual Study Completion Date :

Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: CMS - placebo first Patients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive a placebo (saline) infusion first followed by iron infusion.	Procedure: Venesection Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline. Drug: Iron sucrose Two intravenous infusions, each of 200 mg of iron, separated by one day. Other Names: Venofer Drug: Normal saline Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.
Experimental: CMS - iron Patients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive an iron infusion first followed by placebo (saline) infusion.	Procedure: Venesection Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline. Drug: Iron sucrose Two intravenous infusions, each of 200 mg of iron, separated by one day. Other Names: Venofer Drug: Normal saline Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.
Placebo Comparator: SLR - placebo Sea level residents (SLR) taken to high altitude for one week, and receiving placebo (saline) infusion on Day 3 at high altitude.	Drug: Normal saline Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)
Experimental: SLR - iron Sea level residents (SLR) taken to high altitude for one week, and receiving iron infusion on Day 3 at high altitude.	Drug: Iron sucrose Single intravenous infusion of iron 200 mg Other Names: Venofer