Iron Status and Hypoxic Pulmonary Vascular Responses

This study has been completed.
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: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Lung Hypoxia
Pulmonary Arterial Hypertension
Iron Deficiency
Drug: Intravenous administration of ferric carboxymaltose
Other: Subacute hypoxic exposures

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • ∆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


Secondary Outcome Measures:
  • ∆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 ]

Other Outcome Measures:
  • Fatigue scores in iron-replete versus iron-deficient volunteers [ Time Frame: Assessed at baseline visit ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: February 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Iron-deficient
Healthy volunteers meeting iron-deficient entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures
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-replete
Healthy volunteers meeting iron-replete entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01847352

Locations
United Kingdom
University of Oxford Department of Physiology, Anatomy and Genetics
Oxford, Oxfordshire, United Kingdom, OX1 3PT
Sponsors and Collaborators
University of Oxford
National Institute for Health Research, United Kingdom
Investigators
Principal Investigator: Annabel H Nickol, MBBS PhD University of Oxford
  More Information

Additional Information:
Publications:
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01847352     History of Changes
Other Study ID Numbers: 12/SC/0710
Study First Received: May 1, 2013
Last Updated: May 20, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Hypoxia
Pulmonary hypertension
Iron deficiency
Hypoxic pulmonary vasoconstriction

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Anemia, Iron-Deficiency
Anoxia
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Anemia, Hypochromic
Anemia
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Iron
Ferric Compounds
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 11, 2014