Iron Status and Hypoxic Pulmonary Vascular Responses

May 5, 2016 updated by: University of Oxford

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX1 3PT
        • University of Oxford Department of Physiology, Anatomy and Genetics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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 Names:
  • 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
Other: 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
∆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
During six hours of hypoxia without prior iron infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
∆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
During two six-hour periods of hypoxia; assessments separated by at least a week
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
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
Time Frame: During six hours of hypoxia, at both study assessments
During six hours of hypoxia, at both study assessments

Other Outcome Measures

Outcome Measure
Time Frame
Fatigue scores in iron-replete versus iron-deficient volunteers
Time Frame: Assessed at baseline visit
Assessed at baseline visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

British Heart Foundation
National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Annabel H Nickol, MBBS PhD, University of Oxford

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

May 1, 2013

First Submitted That Met QC Criteria

May 1, 2013

First Posted (Estimate)

May 6, 2013

Study Record Updates

Last Update Posted (Estimate)

May 6, 2016

Last Update Submitted That Met QC Criteria

May 5, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12/SC/0710

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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