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

NCT ID: NCT00952302

Last Updated: 2009-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2008-11-30

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.

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.

Conditions

Pulmonary Hypertension; Mountain Sickness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Venesection

Intervention Type: PROCEDURE

Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline.

Iron sucrose

Intervention Type: DRUG

Two intravenous infusions, each of 200 mg of iron, separated by one day.

Normal saline

Intervention Type: DRUG

Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.

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.

Group Type: EXPERIMENTAL

Venesection

Intervention Type: PROCEDURE

Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline.

Iron sucrose

Intervention Type: DRUG

Two intravenous infusions, each of 200 mg of iron, separated by one day.

Normal saline

Intervention Type: DRUG

Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.

SLR - placebo

Sea level residents (SLR) taken to high altitude for one week, and receiving placebo (saline) infusion on Day 3 at high altitude.

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)

SLR - iron

Sea level residents (SLR) taken to high altitude for one week, and receiving iron infusion on Day 3 at high altitude.

Group Type: EXPERIMENTAL

Iron sucrose

Intervention Type: DRUG

Single intravenous infusion of iron 200 mg

Interventions

Iron sucrose

Single intravenous infusion of iron 200 mg

Intervention Type: DRUG

Normal saline

Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)

Intervention Type: DRUG

Venesection

Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline.

Intervention Type: PROCEDURE

Iron sucrose

Two intravenous infusions, each of 200 mg of iron, separated by one day.

Intervention Type: DRUG

Normal saline

Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.

Intervention Type: DRUG

Other Intervention Names

Venofer; Venofer

Eligibility Criteria

Inclusion Criteria

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

• diagnosis of chronic mountain sickness
• no recent venesection therapy (within 1 year)
• 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

• any other significant medical problem

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Universidad Peruana Cayetano Heredia

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

University of Oxford

Principal Investigators

Peter A Robbins, BMBCh DPhil

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

Universidad Peruana Cayetano Heredia

Lima, , Peru

Countries

Peru

References

Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404.

Reference Type: DERIVED

PMID: 19809026 (View on PubMed)

Other Identifiers

Oxford-Peru-2008

Identifier Type: -

Identifier Source: org_study_id