Iron Deficiency, Lung Hypoxia, Pulmonary Arterial Hypertension
Conditions
Keywords
Hypoxia, Pulmonary hypertension, Iron deficiency, Hypoxic pulmonary vasoconstriction
Brief summary
On exposure to hypoxia (low oxygen) the normal response is for pulmonary arterial systolic blood pressure (PASP, blood pressure through the lungs) to increase. We have previously shown that raising iron by giving an infusion of iron into a vein reduces this pressure rise and that lowering iron by giving a drug that binds iron, magnifies this response. This is potentially a clinically important observation since iron-deficient people may be at increased risk of pulmonary hypertension if exposed transiently or permanently to hypoxia due to lung disease or residence at high altitude; furthermore if this were true then intravenous iron could be an important treatment in this patient group in the event of hypoxic exposure. The observed effects of iron on PASP are likely to be because iron levels affect oxygen sensing. Low iron levels make the body behave as if exposed to low oxygen by inhibiting the breakdown of the family of oxygen-sensing transcription factors, 'hypoxia inducible factor' or HIF. This includes one of the body's normal responses to low oxygen levels - raising blood pressure through the lungs. This study will answer the question (1) do iron-deficient volunteers have a greater rise in PASP with hypoxia than those who are iron-replete, and (2) does giving intravenous iron cause a greater reduction in the rise in PASP in those who are iron-deficient than iron-replete? The purpose of this study is not to test the safety or clinical efficacy of iron which is already known.
Interventions
DRUGIntravenous administration of ferric carboxymaltose
Intravenous administration of ferric carboxymaltose 15mg/kg up to a maximum dose of 1000mg
OTHERSubacute hypoxic exposures
Exposure to six hours of isocapnic hypoxia with end-tidal partial pressure of oxygen clamped at 55 Torr, with and without prior iron infusion
Sponsors
National Institute for Health Research, United Kingdom
British Heart Foundation
University of Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to give informed consent for participation in the study * Men and women aged 18 years or older and generally in good health * Detectable tricuspid regurgitation on echocardiography during both normoxia and hypoxia enabling measurement of pulmonary arterial pressure * For iron-deficient volunteers: ferritin ≤15microg/L and transferrin saturation \<16% * For iron-replete volunteers: ferritin ≥20microg/L and transferrin saturation ≥20%
Exclusion criteria
* Haemoglobin \<8.0g/dl * Haemoglobinopathy * Iron overload defined as ferritin \>300microg/L * Hypoxia at rest or on walking (SaO2 \<94%) or significant comorbidity that may affect haematinics, pulmonary vascular or ventilatory responses, e.g. current infection, a chronic inflammatory condition, known cardiovalvular lesion or pulmonary hypertension, uncontrolled asthma or chronic obstructive pulmonary disease * Exposure to high altitude (\>2,500m) within the previous six weeks or air travel \>4 hours within the previous week * Iron supplementation or blood transfusion within the previous 6 weeks * Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ∆PASP in iron-replete compared to iron-deficient volunteers | During six hours of hypoxia without prior iron infusion | Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ∆PASP, with versus without prior iron infusion, in iron-replete compared to iron-deficient volunteers | During two six-hour periods of hypoxia; assessments separated by at least a week | Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers, with versus without a prior iron infusion |
| Blood parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers | After six hours of hypoxia, at both study assessments | — |
| Ventilation parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers | During six hours of hypoxia, at both study assessments | — |
Other
| Measure | Time frame |
|---|---|
| Fatigue scores in iron-replete versus iron-deficient volunteers | Assessed at baseline visit |
Countries
United Kingdom
Outcome results
None listed