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

August 4, 2009 updated by: University of Oxford

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

33

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Peru
      • Lima, Peru, 31
        • Universidad Peruana Cayetano Heredia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

SLR ARM

Inclusion Criteria:

  • sea level natives of lowland ancestry
  • generally in good health
  • detectable tricuspid regurgitation on echocardiography

Exclusion Criteria:

  • any significant medical problem
  • known susceptibility to high altitude pulmonary or cerebral oedema
  • taking medications or iron supplements

CMS ARM

Inclusion Criteria:

  • diagnosis of chronic mountain sickness
  • no recent venesection therapy (within 1 year)
  • detectable tricuspid regurgitation on echocardiography

Exclusion Criteria:

  • any other significant medical problem

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.
Drug: Iron sucrose
Single intravenous infusion of iron 200 mg
Other Names:
  • Venofer
Drug: Normal saline
Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)
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.
Drug: Iron sucrose
Single intravenous infusion of iron 200 mg
Other Names:
  • Venofer
Drug: Normal saline
Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)
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)
Drug: Normal saline
Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.
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
Drug: Iron sucrose
Two intravenous infusions, each of 200 mg of iron, separated by one day.
Other Names:
  • Venofer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in pulmonary artery systolic pressure
Time Frame: One week (SLR arm) and one month (CMS arm)
One week (SLR arm) and one month (CMS arm)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Universidad Peruana Cayetano Heredia

Investigators

  • Principal Investigator: Peter A Robbins, BMBCh DPhil, University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

August 4, 2009

First Submitted That Met QC Criteria

August 4, 2009

First Posted (Estimate)

August 6, 2009

Study Record Updates

Last Update Posted (Estimate)

August 6, 2009

Last Update Submitted That Met QC Criteria

August 4, 2009

Last Verified

August 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Oxford-Peru-2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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