Clinical trial NCT00960921: Study of the Effects of Iron on Lung Blood Pressure at High Altitude
Official title: Study of the Effects of Iron Supplementation on High Altitude Pulmonary Hypertension.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary artery pressure
Hypoxia
Iron
Hypoxia-inducible factor
High altitude
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
First posted: 2009-08-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in pulmonary artery systolic pressure
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Bishkek
country: Kyrgyzstan
facility: Institute of Molecular Biology and Medicine
Study officials:
affiliation: University of Oxford
name: Peter A Robbins, DPhil BM BCh
role: PRINCIPAL_INVESTIGATOR
References: