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

This study has been completed.
Sponsor:
Collaborator:
Universidad Peruana Cayetano Heredia
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00952302
First received: August 4, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  Purpose

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 Intervention
Pulmonary Hypertension
Mountain Sickness
Drug: Iron sucrose
Drug: Normal saline
Procedure: Venesection

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Change in pulmonary artery systolic pressure [ Time Frame: One week (SLR arm) and one month (CMS arm) ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: October 2008
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Venofer

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00952302

Locations
Peru
Universidad Peruana Cayetano Heredia
Lima, Peru, 31
Sponsors and Collaborators
University of Oxford
Universidad Peruana Cayetano Heredia
Investigators
Principal Investigator: Peter A Robbins, BMBCh DPhil University of Oxford
  More Information

No publications provided by University of Oxford

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ms Heather House, Head of Clinical Trials and Research Governance, University of Oxford
ClinicalTrials.gov Identifier: NCT00952302     History of Changes
Other Study ID Numbers: Oxford-Peru-2008
Study First Received: August 4, 2009
Last Updated: August 4, 2009
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Hypoxia
Iron
Hypoxia-Inducible Factor 1
Chronic mountain sickness

Additional relevant MeSH terms:
Altitude Sickness
Hypertension
Hypertension, Pulmonary
Respiration Disorders
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Ferric oxide, saccharated
Ferric Compounds
Iron
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014