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NCT Number: NCT01847352

Iron Status and Hypoxic Pulmonary Vascular Responses

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.

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Key information

Conditions

Lung Hypoxia Cardiovascular Diseases Hypertension Hypertension, Pulmonary Hypoxia Iron Deficiencies Iron Deficiency Iron Metabolism Disorders Lung Diseases Metabolic Diseases Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Pulmonary Arterial Hypertension Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Oxford Department of Physiology, Anatomy and Genetics

Oxford, Oxfordshire, OX1 3PT, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Intravenous administration of ferric carboxymaltose

Drug

Intravenous administration of ferric carboxymaltose 15mg/kg up to a maximum dose of 1000mg

Other names: Ferinject

Subacute hypoxic exposures

Other

Exposure to six hours of isocapnic hypoxia with end-tidal partial pressure of oxygen clamped at 55 Torr, with and without prior iron infusion

Other names: Hypoxia, Hypoxic challenge

Primary outcomes

  1. ∆PASP in iron-replete compared to iron-deficient volunteers

    Time frame: 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 outcomes

  1. ∆PASP, with versus without prior iron infusion, in iron-replete compared to iron-deficient volunteers

    Time frame: 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

  2. Blood parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers

    Time frame: After six hours of hypoxia, at both study assessments

  3. Ventilation parameter changes, pre- versus post-intravenous iron, in iron-replete compared to iron-deficient volunteers

    Time frame: During six hours of hypoxia, at both study assessments

Other outcomes

  1. Fatigue scores in iron-replete versus iron-deficient volunteers

    Time frame: Assessed at baseline visit

Sponsors and collaborators

Lead sponsor

University of Oxford

Other

Collaborators

  • British Heart Foundation
  • National Institute for Health Research, United Kingdom

Registry information

Official study title

Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
May 6, 2013
Registry last updated
May 6, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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