Study of the Effects of Iron on Lung Blood Pressure at High Altitude

Study of the Effects of Iron Supplementation on High Altitude Pulmonary Hypertension.

Body iron levels may be important in determining how the blood pressure in the lungs changes in response to low oxygen levels. At high altitude, where oxygen levels are low, some patients develop elevated lung blood pressure. The investigators hypothesize that, in high altitude residents with elevated lung blood pressure, iron supplementation will cause a reduction in lung blood pressure.

Study Overview

• Status: Withdrawn
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: Iron sucrose; Drug: Normal saline

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 reduced iron availability (by chelation with desferrioxamine) and potentiated by iron supplementation. In humans, laboratory experiments lasting eight hours have shown that acute iron supplementation blunts the pulmonary vascular response to hypoxia, while acute iron chelation with desferrioxamine enhances the response.

These findings suggest that iron may also affect the pulmonary vascular response to hypoxia over longer time periods. The purpose of this study, which will take place at high altitude in Kyrgyzstan, is to investigate whether iron supplementation can reduce pulmonary artery pressure in patients with established high altitude pulmonary hypertension.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Kyrgyzstan
  • Bishkek, Kyrgyzstan, 720040
    • Institute of Molecular Biology and Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High altitude natives, currently resident at high altitude
• Pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg)
• Pulmonary artery systolic pressure measurable using Doppler echocardiography

Exclusion Criteria:

• Clinical evidence or history of major co-morbidity
• Recent changes to relevant medications, or taking iron/vitamin supplements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron group; Patients with high altitude pulmonary hypertension receive six intravenous infusions of iron sucrose, administered on days 0, 4, 8, 12, 16 and 20 of the study. The total study period is 28 days. Pulmonary artery systolic pressure is measured before each infusion, and again on day 28.	Drug: Iron sucrose; An intravenous infusion of 100 mg of iron is administered on days 0, 4, 8, 12, 16 and 20 of the study, giving a total of six iron infusions for each participant in the iron group over the course of the 28-day study period.; Other Names: Venofer (iron sucrose)
Placebo Comparator: Saline group; Patients with high altitude pulmonary hypertension receive six intravenous infusions of normal saline, administered on days 0, 4, 8, 12, 16 and 20 of the study. The total study period is 28 days. Pulmonary artery systolic pressure is measured before each infusion, and again on day 28.	Drug: Normal saline; An intravenous infusion of 100 ml of normal (0.9 %) saline is administered on days 0, 4, 8, 12, 16 and 20 of the study, giving a total of six saline (placebo) infusions for each participant in the saline group over the course of the 28-day study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in pulmonary artery systolic pressure	28 days

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
• Investigators: Principal Investigator: Peter A Robbins, DPhil BM BCh, University of Oxford

Study record dates

Study Registration Dates

• First Submitted: August 17, 2009
• First Submitted That Met QC Criteria: August 17, 2009
• First Posted (Estimate): August 18, 2009

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 12, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Iron; Hypoxia; Pulmonary artery pressure; High altitude; Hypoxia-inducible factor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Trace Elements; Micronutrients; Hematinics; Iron; Ferric Oxide, Saccharated
• Other Study ID Numbers: Oxford-Kyrgyzstan-2009