Iron Status and Hypoxic Pulmonary Vascular Responses

This study is currently recruiting participants.
Verified May 2013 by University of Oxford
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01847352
First received: May 1, 2013
Last updated: NA
Last verified: May 2013
History: No changes posted

May 1, 2013
May 1, 2013
February 2013
February 2015   (final data collection date for primary outcome measure)
∆PASP in iron-replete compared to iron-deficient volunteers [ Time Frame: During six hours of hypoxia without prior iron infusion ] [ Designated as safety issue: No ]
Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers
Same as current
No Changes Posted
  • ∆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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: After six hours of hypoxia, at both study assessments ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Same as current
Fatigue scores in iron-replete versus iron-deficient volunteers [ Time Frame: Assessed at baseline visit ] [ Designated as safety issue: No ]
Same as current
 
Iron Status and Hypoxic Pulmonary Vascular Responses
Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron

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.

Not Provided
Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
  • Lung Hypoxia
  • Pulmonary Arterial Hypertension
  • Iron Deficiency
  • Drug: Intravenous administration of ferric carboxymaltose
    Intravenous administration of ferric carboxymaltose 15mg/kg up to a maximum dose of 1000mg
    Other Name: Ferinject
  • Other: Subacute 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
    Other Names:
    • Hypoxia
    • Hypoxic challenge
  • Iron-deficient
    Healthy volunteers meeting iron-deficient entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures
    Interventions:
    • Drug: Intravenous administration of ferric carboxymaltose
    • Other: Subacute hypoxic exposures
  • Iron-replete
    Healthy volunteers meeting iron-replete entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures
    Interventions:
    • Drug: Intravenous administration of ferric carboxymaltose
    • Other: Subacute hypoxic exposures

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
28
February 2015
February 2015   (final data collection date for primary outcome measure)

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 <15% for men and <12% for women
  • 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
Both
18 Years and older
Yes
Contact: Matthew C Frise, BMBCh +44(0)1865282357 matthew.frise@dpag.ox.ac.uk
Contact: Annabel H Nickol, MBBS PhD +44(0)1865857168 annabel.nickol@ndm.ox.ac.uk
United Kingdom
 
NCT01847352
12/SC/0710
No
University of Oxford
University of Oxford
National Institute for Health Research, United Kingdom
Principal Investigator: Annabel H Nickol, MBBS PhD University of Oxford
University of Oxford
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP