Lung HypoxiaNCT01847352
Iron Status and Hypoxic Pulmonary Vascular Responses
A study testing Intravenous administration of ferric carboxymaltose and Subacute hypoxic exposures in people with Lung Hypoxia and Pulmonary Arterial Hypertension, run by University of Oxford at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Lung Hypoxia, Pulmonary Arterial Hypertension, Iron Deficiency
- What is being tested?
- Intravenous administration of ferric carboxymaltose and Subacute hypoxic exposures
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2013to Apr 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Oxford Department of Physiology, Anatomy and Genetics
Oxford, Oxfordshire, OX1 3PT
About this study
Official title: 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.
- Being tested
- Intravenous administration of ferric carboxymaltose, Subacute hypoxic exposures
- Keywords
- Hypoxia, Pulmonary hypertension, Iron deficiency, Hypoxic pulmonary vasoconstriction
- Medical subject headings
- Pulmonary Arterial Hypertension, Iron Deficiencies, Hypoxia, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous administration of ferric carboxymaltoseDrug
Also called Ferinject
Intravenous administration of ferric carboxymaltose 15mg/kg up to a maximum dose of 1000mg
Subacute hypoxic exposuresOther
Also called Hypoxia, Hypoxic challenge
Exposure to six hours of isocapnic hypoxia with end-tidal partial pressure of oxygen clamped at 55 Torr, with and without prior iron infusion
| Study group | Role | What they receive |
|---|---|---|
| Iron-deficient | Other | Healthy volunteers meeting iron-deficient entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures Receives: Drug: Intravenous administration of ferric carboxymaltose; Other: Subacute hypoxic exposures |
| Iron-replete | Other | Healthy volunteers meeting iron-replete entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures Receives: Drug: Intravenous administration of ferric carboxymaltose; Other: Subacute hypoxic exposures |
What is being measured
The primary outcome is the main question the study is designed to answer.
∆PASP in iron-replete compared to iron-deficient volunteers
Difference between the rise in pulmonary artery systolic pressure during a hypoxic challenge in iron-replete compared to iron-deficient volunteers
Measured: During six hours of hypoxia without prior iron infusion
Secondary outcomes (3)
∆PASP, with versus without prior iron infusion, in iron-replete compared to iron-deficient volunteers
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
Measured: 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
Measured: 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
Measured: During six hours of hypoxia, at both study assessments
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2013 (estimated)
- Study startFeb 2013
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Lung HypoxiaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, British Heart Foundation
- Responsible party
- Sponsor
- Investigators
- Annabel H Nickol, MBBS PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01847352
- Sponsor's protocol ID
- 12/SC/0710
- Status last verified
- May 2016
- First submitted
- 1 May 2013
- Last updated
- 6 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27.
PubMed 18955380Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404.
PubMed 19809026Talbot NP, Smith TG, Privat C, Nickol AH, Rivera-Ch M, Leon-Velarde F, Dorrington KL, Robbins PA. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial. High Alt Med Biol. 2011 Fall;12(3):265-9. doi: 10.1089/ham.2011.1005.
PubMed 21962070Balanos GM, Dorrington KL, Robbins PA. Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1. J Appl Physiol (1985). 2002 Jun;92(6):2501-7. doi: 10.1152/japplphysiol.00965.2001.
PubMed 12015365Frise MC, Cheng HY, Nickol AH, Curtis MK, Pollard KA, Roberts DJ, Ratcliffe PJ, Dorrington KL, Robbins PA. Clinical iron deficiency disturbs normal human responses to hypoxia. J Clin Invest. 2016 Jun 1;126(6):2139-50. doi: 10.1172/JCI85715. Epub 2016 May 3.
PubMed 27140401
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Endogenous Iron Status on Hypoxic Pulmonary Vascular Responses and Their Attenuation by Intravenous Iron
- ClinicalTrials.gov ID
- NCT01847352
- Acronym / sponsor ID
- 12/SC/0710
- Keywords
- Hypoxia, Pulmonary hypertension, Iron deficiency, Hypoxic pulmonary vasoconstriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, British Heart Foundation
- Study start
- Feb 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 6 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Iron-deficient | Other | Drug: Intravenous administration of ferric carboxymaltose, Other: Subacute hypoxic exposuresHealthy volunteers meeting iron-deficient entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures |
| Iron-replete | Other | Drug: Intravenous administration of ferric carboxymaltose, Other: Subacute hypoxic exposuresHealthy volunteers meeting iron-replete entry criteria; Intravenous administration of ferric carboxymaltose; Subacute hypoxic exposures |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous administration of ferric carboxymaltoseAlso: FerinjectIntravenous administration of ferric carboxymaltose 15mg/kg up to a maximum dose of 1000mg | Drug | Iron-deficient, Iron-replete |
| Subacute hypoxic exposuresAlso: Hypoxia, Hypoxic challengeExposure to six hours of isocapnic hypoxia with end-tidal partial pressure of oxygen clamped at 55 Torr, with and without prior iron infusion | Other | Iron-deficient, Iron-replete |
Primary outcome
∆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
3 secondary outcomes
∆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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2016.
- Background: PubMed 18955380Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27.
- Background: PubMed 19809026Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404.
- Background: PubMed 21962070Talbot NP, Smith TG, Privat C, Nickol AH, Rivera-Ch M, Leon-Velarde F, Dorrington KL, Robbins PA. Intravenous iron supplementation may protect against acute mountain sickness: a randomized, double-blinded, placebo-controlled trial. High Alt Med Biol. 2011 Fall;12(3):265-9. doi: 10.1089/ham.2011.1005.
- Background: PubMed 12015365Balanos GM, Dorrington KL, Robbins PA. Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1. J Appl Physiol (1985). 2002 Jun;92(6):2501-7. doi: 10.1152/japplphysiol.00965.2001.
- Results publication: PubMed 27140401Frise MC, Cheng HY, Nickol AH, Curtis MK, Pollard KA, Roberts DJ, Ratcliffe PJ, Dorrington KL, Robbins PA. Clinical iron deficiency disturbs normal human responses to hypoxia. J Clin Invest. 2016 Jun 1;126(6):2139-50. doi: 10.1172/JCI85715. Epub 2016 May 3.
- Research Group WebsiteLink provided by the sponsor.
- Funding Body WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annabel H Nickol, MBBS PhD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous administration of ferric carboxymaltose and Subacute hypoxic exposures in people with Lung Hypoxia and Pulmonary Arterial Hypertension, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
∆PASP in iron-replete compared to iron-deficient volunteers (time frame: During six hours of hypoxia without prior iron infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01847352, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2016.