Pulmonary HypertensionNCT00952302
Study of the Effects of Iron Levels on the Lungs at High Altitude
A study testing Iron sucrose, Normal saline and Venesection in people with Pulmonary Hypertension and Mountain Sickness, run by University of Oxford at 1 site in Peru.
Trial summary
The study hypothesis is that body iron levels are important in determining the increase in lung blood pressure that occurs in response to low oxygen levels. The purpose of this study is to determine whether this is true at high altitude, where oxygen levels are low. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension, Mountain Sickness
- What is being tested?
- Iron sucrose, Normal saline and Venesection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 sitePeru
- Study dates
- Oct 2008to Nov 2008
- 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 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- sea level natives of lowland ancestry
- generally in good health
- detectable tricuspid regurgitation on echocardiography
- diagnosis of chronic mountain sickness
- no recent venesection therapy (within 1 year)
- detectable tricuspid regurgitation on echocardiography
Who cannot join
- any significant medical problem
- known susceptibility to high altitude pulmonary or cerebral oedema
- taking medications or iron supplements
- CMS ARM
- any other significant medical problem
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Physiology Study Investigating the Effects of Supplementation and Depletion of Iron on Hypoxia-related Pulmonary Hypertension
The study hypothesis is that body iron levels are important in determining the increase in lung blood pressure that occurs in response to low oxygen levels. The purpose of this study is to determine whether this is true at high altitude, where oxygen levels are low.
Read the detailed description
Pulmonary hypertensive disorders frequently complicate hypoxic lung disease and worsen patient survival. Hypoxia-induced pulmonary hypertension is also a major cause of morbidity at high altitude. Hypoxia causes pulmonary hypertension through hypoxic pulmonary vasoconstriction and vascular remodelling. These processes are thought to be regulated at least in part by the hypoxia-inducible factor (HIF) family of transcription factors, which coordinate intracellular responses to hypoxia throughout the body.
HIF is regulated through a cellular degradation process that requires iron as an obligate cofactor. In cultured cells HIF degradation is inhibited by reduction in iron (by chelation with desferrioxamine) and potentiated by iron supplementation. In humans, we have recently shown that, in laboratory experiments lasting 8 hours, acute iron supplementation blunts the pulmonary vascular response to hypoxia, while acute iron chelation with desferrioxamine enhances the response.
This suggests that iron may also affect the pulmonary artery pressure response to hypoxia over longer time periods. The purpose of this study is to investigate this link between iron and the pulmonary artery pressure response to hypoxia, through a study conducted at high altitude allowing concurrent exposure of larger numbers of participants to environmental hypoxia. We wish to explore the extent and the time-course of the effect of iron on pulmonary artery pressure. Cerro de Pascu (4,340 m) in Peru provides the unique ability to make rapid transitions from sea level to high altitude (6-8 hours by road), together with the requisite research facilities. Also, one part of this study involves recruitment of patients with chronic mountain sickness, of whom there are many living in Cerro de Pasco.
- Conditions
- Pulmonary Hypertension, Mountain Sickness
- Being tested
- Iron sucrose, Normal saline, Venesection
- Keywords
- Hypoxia, Iron, Hypoxia-Inducible Factor 1, Chronic mountain sickness
- Medical subject headings
- Hypertension, Pulmonary, Altitude Sickness, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron sucroseDrug
Also called Venofer
Single intravenous infusion of iron 200 mg
Normal salineDrug
Single intravenous infusion of normal 0.9% saline 100 mls (as placebo)
VenesectionProcedure or surgery
Isolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline.
Iron sucroseDrug
Also called Venofer
Two intravenous infusions, each of 200 mg of iron, separated by one day.
Normal salineDrug
Two intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day.
| Study group | Role | What they receive |
|---|---|---|
| CMS - placebo first | Placebo comparator | Patients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive a placebo (saline) infusion first followed by iron infusion. Receives: Procedure: Venesection; Drug: Iron sucrose; Drug: Normal saline |
| CMS - iron | Experimental | Patients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive an iron infusion first followed by placebo (saline) infusion. Receives: Procedure: Venesection; Drug: Iron sucrose; Drug: Normal saline |
| SLR - placebo | Placebo comparator | Sea level residents (SLR) taken to high altitude for one week, and receiving placebo (saline) infusion on Day 3 at high altitude. Receives: Drug: Normal saline |
| SLR - iron | Experimental | Sea level residents (SLR) taken to high altitude for one week, and receiving iron infusion on Day 3 at high altitude. Receives: Drug: Iron sucrose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pulmonary artery systolic pressure
Measured: One week (SLR arm) and one month (CMS arm)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2009 (estimated)
- Study startOct 2008
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad Peruana Cayetano Heredia
- Investigators
- Peter A Robbins, BMBCh DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00952302
- Sponsor's protocol ID
- Oxford-Peru-2008
- Status last verified
- Aug 2009
- First submitted
- 4 Aug 2009
- Last updated
- 6 Aug 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Smith 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 19809026
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiology Study Investigating the Effects of Supplementation and Depletion of Iron on Hypoxia-related Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT00952302
- Acronym / sponsor ID
- Oxford-Peru-2008
- Conditions
- Pulmonary Hypertension, Mountain Sickness
- Keywords
- Hypoxia, Iron, Hypoxia-Inducible Factor 1, Chronic mountain sickness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Universidad Peruana Cayetano Heredia
- Study start
- Oct 2008
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 6 Aug 2009 (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.
The study hypothesis is that body iron levels are important in determining the increase in lung blood pressure that occurs in response to low oxygen levels. The purpose of this study is to determine whether this is true at high altitude, where oxygen levels are low.
Detailed description
Pulmonary hypertensive disorders frequently complicate hypoxic lung disease and worsen patient survival. Hypoxia-induced pulmonary hypertension is also a major cause of morbidity at high altitude. Hypoxia causes pulmonary hypertension through hypoxic pulmonary vasoconstriction and vascular remodelling. These processes are thought to be regulated at least in part by the hypoxia-inducible factor (HIF) family of transcription factors, which coordinate intracellular responses to hypoxia throughout the body.
HIF is regulated through a cellular degradation process that requires iron as an obligate cofactor. In cultured cells HIF degradation is inhibited by reduction in iron (by chelation with desferrioxamine) and potentiated by iron supplementation. In humans, we have recently shown that, in laboratory experiments lasting 8 hours, acute iron supplementation blunts the pulmonary vascular response to hypoxia, while acute iron chelation with desferrioxamine enhances the response.
This suggests that iron may also affect the pulmonary artery pressure response to hypoxia over longer time periods. The purpose of this study is to investigate this link between iron and the pulmonary artery pressure response to hypoxia, through a study conducted at high altitude allowing concurrent exposure of larger numbers of participants to environmental hypoxia. We wish to explore the extent and the time-course of the effect of iron on pulmonary artery pressure. Cerro de Pascu (4,340 m) in Peru provides the unique ability to make rapid transitions from sea level to high altitude (6-8 hours by road), together with the requisite research facilities. Also, one part of this study involves recruitment of patients with chronic mountain sickness, of whom there are many living in Cerro de Pasco.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CMS - placebo first | Placebo comparator | Procedure: Venesection, Drug: Iron sucrose, Drug: Normal salinePatients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive a placebo (saline) infusion first followed by iron infusion. |
| CMS - iron | Experimental | Procedure: Venesection, Drug: Iron sucrose, Drug: Normal salinePatients with chronic mountain sickness (CMS) who are venesected and studied for several weeks. In the final crossover period of the study, patients receive an iron infusion first followed by placebo (saline) infusion. |
| SLR - placebo | Placebo comparator | Drug: Normal salineSea level residents (SLR) taken to high altitude for one week, and receiving placebo (saline) infusion on Day 3 at high altitude. |
| SLR - iron | Experimental | Drug: Iron sucroseSea level residents (SLR) taken to high altitude for one week, and receiving iron infusion on Day 3 at high altitude. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- sea level natives of lowland ancestry
- generally in good health
- detectable tricuspid regurgitation on echocardiography
- diagnosis of chronic mountain sickness
- no recent venesection therapy (within 1 year)
Key exclusion criteria (5 listed)
- any significant medical problem
- known susceptibility to high altitude pulmonary or cerebral oedema
- taking medications or iron supplements
- CMS ARM
- any other significant medical problem
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 |
|---|---|---|
| Iron sucroseAlso: VenoferSingle intravenous infusion of iron 200 mg | Drug | SLR - iron |
| Normal salineSingle intravenous infusion of normal 0.9% saline 100 mls (as placebo) | Drug | SLR - placebo |
| VenesectionIsolvolaemic venesection of total 2 litres of blood - 500 mls each day for 4 days, replaced with normal saline. | Procedure or surgery | CMS - iron, CMS - placebo first |
| Iron sucroseAlso: VenoferTwo intravenous infusions, each of 200 mg of iron, separated by one day. | Drug | CMS - iron, CMS - placebo first |
| Normal salineTwo intravenous infusions of normal 0.9% saline 100 mls (as placebo), separated by one day. | Drug | CMS - iron, CMS - placebo first |
Primary outcome
Change in pulmonary artery systolic pressure
Time frame: One week (SLR arm) and one month (CMS arm)
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 Aug 2009.
- Derived from this study: 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.
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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.
Peter A Robbins, BMBCh DPhil 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 Iron sucrose, Normal saline and Venesection in people with Pulmonary Hypertension and Mountain Sickness, run by University of Oxford at 1 site in Peru.
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 6 inclusion and 5 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 Aug 2009. 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 Peru. 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. Some participants in this study may receive a placebo. 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?
Change in pulmonary artery systolic pressure (time frame: One week (SLR arm) and one month (CMS arm)). 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 NCT00952302, which also lists 1 linked publication.
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 Aug 2009.