Iron DeficiencyNCT02308449
Iron Status and Human Metabolism
A study testing Ferric carboxymaltose in people with Iron Deficiency, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Iron deficiency is common in cardiorespiratory diseases and appears to contribute to a worse outcome. This human physiology study will examine the extent to which human skeletal muscle metabolism and exercise physiology are impaired by iron deficiency. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Iron Deficiency
- What is being tested?
- Ferric carboxymaltose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2014to Jan 2016
- 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
- For iron-deficient volunteers: ferritin ≤ 15 microg/L and transferrin saturation < 16%
- For iron-replete volunteers: ferritin ≥ 20 microg/L and transferrin saturation ≥ 20%
Who cannot join
- Haemoglobin < 8.0 g/dL
- Haemoglobinopathy
- Iron overload, defined as ferritin > 300 microg/L
- Hypoxaemia (SpO2 < 94%) or significant co-morbidity that may affect haematinics, metabolic or ventilatory responses
- Iron supplementation or blood transfusion within the previous 6 weeks
- Pregnancy or breast feeding
Show all 9Show fewer
- Inability to exercise isolated calf muscle using a pedal or on a bicycle ergometer
- Contraindication to magnetic resonance spectroscopy exposure such as metallic implant
- Contraindication to receiving intravenous ferric carboxymaltose
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Oxford OCMR & CCRF, John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
About this study
Official title: Effects of Endogenous Iron Status and Intravenous Iron on Human Skeletal Muscle Metabolism at Rest and During Exercise
Iron deficiency is common in cardiorespiratory diseases and appears to contribute to a worse outcome. This human physiology study will examine the extent to which human skeletal muscle metabolism and exercise physiology are impaired by iron deficiency.
Read the detailed description
This is a prospective double-blind randomised controlled study of the effect of endogenous iron status on skeletal muscle metabolism and exercise physiology. 32 healthy volunteers will take part, half of whom will be iron-deficient. The study involves a screening visit and two half-day visits during which assessments are performed. 50% of each group will be randomised to receive iron-repletion with ferric carboxymaltose at the end of the first experimental visit before returning to repeat identical assessments around one week later. This approach will make it possible to explore whether baseline differences in skeletal muscle metabolism are explained by differences in iron status per se, whilst controlling for any learning effect during participation in the study.
- Conditions
- Iron Deficiency
- Being tested
- Ferric carboxymaltose, Sodium chloride (placebo)
- Medical subject headings
- Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric carboxymaltoseDrug
Also called Ferinject
Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride
Sodium chloride (placebo)Drug
Also called Normal saline
Infusion of 250 mL 0.9% sodium chloride
| Study group | Role | What they receive |
|---|---|---|
| Iron-deficient, given placebo | Placebo comparator | Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit Receives: Drug: Sodium chloride (placebo) |
| Iron-deficient, given iron | Active comparator | Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit Receives: Drug: Ferric carboxymaltose |
| Iron-replete, given placebo | Placebo comparator | Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit Receives: Drug: Sodium chloride (placebo) |
| Iron-replete, given iron | Active comparator | Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit Receives: Drug: Ferric carboxymaltose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phosphocreatine depletion during small muscle mass exercise
Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy
Measured: 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Secondary outcomes (3)
Cardiopulmonary exercise test performance
Blood lactate and cardiorespiratory parameters during moderate large skeletal muscle mass exercise, assessed with cardiopulmonary exercise testing
Measured: Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Muscle biopsy findings
Skeletal muscle characteristics, assessed by minimally-invasive muscle biopsy (not a compulsory part of the protocol)
Measured: Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart)
Participant reported symptoms
Measures of fatigue, restless-legs syndrome and well-being assessed by self-reported questionnaires
Measured: At study screening visit compared to four weeks following infusion of iron or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Iron DeficiencyStudies 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Peter A Robbins, DPhil, Study director, University of OxfordMatthew C Frise, MRCP, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308449
- Sponsor's protocol ID
- 13/SC/0439
- Status last verified
- Jul 2022
- First submitted
- 21 Nov 2014
- Last updated
- 19 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Formenti F, Constantin-Teodosiu D, Emmanuel Y, Cheeseman J, Dorrington KL, Edwards LM, Humphreys SM, Lappin TR, McMullin MF, McNamara CJ, Mills W, Murphy JA, O'Connor DF, Percy MJ, Ratcliffe PJ, Smith TG, Treacy M, Frayn KN, Greenhaff PL, Karpe F, Clarke K, Robbins PA. Regulation of human metabolism by hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12722-7. doi: 10.1073/pnas.1002339107. Epub 2010 Jun 28.
PubMed 20616028Smith 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 19809026Smith 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, Brooks JT, Balanos GM, Lappin TR, Layton DM, Leedham DL, Liu C, Maxwell PH, McMullin MF, McNamara CJ, Percy MJ, Pugh CW, Ratcliffe PJ, Talbot NP, Treacy M, Robbins PA. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006 Jul;3(7):e290. doi: 10.1371/journal.pmed.0030290.
PubMed 16768548Finch CA, Gollnick PD, Hlastala MP, Miller LR, Dillmann E, Mackler B. Lactic acidosis as a result of iron deficiency. J Clin Invest. 1979 Jul;64(1):129-37. doi: 10.1172/JCI109431.
PubMed 447849Frise MC, Holdsworth DA, Johnson AW, Chung YJ, Curtis MK, Cox PJ, Clarke K, Tyler DJ, Roberts DJ, Ratcliffe PJ, Dorrington KL, Robbins PA. Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation. Sci Rep. 2022 Jan 19;12(1):998. doi: 10.1038/s41598-021-03968-4.
PubMed 35046429
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Endogenous Iron Status and Intravenous Iron on Human Skeletal Muscle Metabolism at Rest and During Exercise
- ClinicalTrials.gov ID
- NCT02308449
- Acronym / sponsor ID
- 13/SC/0439
- Conditions
- Iron Deficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- British Heart Foundation, National Institute for Health Research, United Kingdom
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 4 Dec 2014 (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.
Iron deficiency is common in cardiorespiratory diseases and appears to contribute to a worse outcome. This human physiology study will examine the extent to which human skeletal muscle metabolism and exercise physiology are impaired by iron deficiency.
Detailed description
This is a prospective double-blind randomised controlled study of the effect of endogenous iron status on skeletal muscle metabolism and exercise physiology. 32 healthy volunteers will take part, half of whom will be iron-deficient. The study involves a screening visit and two half-day visits during which assessments are performed. 50% of each group will be randomised to receive iron-repletion with ferric carboxymaltose at the end of the first experimental visit before returning to repeat identical assessments around one week later. This approach will make it possible to explore whether baseline differences in skeletal muscle metabolism are explained by differences in iron status per se, whilst controlling for any learning effect during participation in the study.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Iron-deficient, given placebo | Placebo comparator | Drug: Sodium chloride (placebo)Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit |
| Iron-deficient, given iron | Active comparator | Drug: Ferric carboxymaltoseIron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit |
| Iron-replete, given placebo | Placebo comparator | Drug: Sodium chloride (placebo)Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit |
| Iron-replete, given iron | Active comparator | Drug: Ferric carboxymaltoseIron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 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
- For iron-deficient volunteers: ferritin ≤ 15 microg/L and transferrin saturation < 16%
- For iron-replete volunteers: ferritin ≥ 20 microg/L and transferrin saturation ≥ 20%
Key exclusion criteria (9 listed)
- Haemoglobin < 8.0 g/dL
- Haemoglobinopathy
- Iron overload, defined as ferritin > 300 microg/L
- Hypoxaemia (SpO2 < 94%) or significant co-morbidity that may affect haematinics, metabolic or ventilatory responses
- Iron supplementation or blood transfusion within the previous 6 weeks
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 |
|---|---|---|
| Ferric carboxymaltoseAlso: FerinjectInfusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride | Drug | Iron-deficient, given iron, Iron-replete, given iron |
| Sodium chloride (placebo)Also: Normal salineInfusion of 250 mL 0.9% sodium chloride | Drug | Iron-deficient, given placebo, Iron-replete, given placebo |
Primary outcome
Phosphocreatine depletion during small muscle mass exercise
Time frame: 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy
3 secondary outcomes
Cardiopulmonary exercise test performance
Time frame: Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Muscle biopsy findings
Time frame: Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart)
Participant reported symptoms
Time frame: At study screening visit compared to four weeks following infusion of iron or placebo
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 19 Jul 2022.
- Background: PubMed 20616028Formenti F, Constantin-Teodosiu D, Emmanuel Y, Cheeseman J, Dorrington KL, Edwards LM, Humphreys SM, Lappin TR, McMullin MF, McNamara CJ, Mills W, Murphy JA, O'Connor DF, Percy MJ, Ratcliffe PJ, Smith TG, Treacy M, Frayn KN, Greenhaff PL, Karpe F, Clarke K, Robbins PA. Regulation of human metabolism by hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12722-7. doi: 10.1073/pnas.1002339107. Epub 2010 Jun 28.
- 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 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 16768548Smith TG, Brooks JT, Balanos GM, Lappin TR, Layton DM, Leedham DL, Liu C, Maxwell PH, McMullin MF, McNamara CJ, Percy MJ, Pugh CW, Ratcliffe PJ, Talbot NP, Treacy M, Robbins PA. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006 Jul;3(7):e290. doi: 10.1371/journal.pmed.0030290.
- Background: PubMed 447849Finch CA, Gollnick PD, Hlastala MP, Miller LR, Dillmann E, Mackler B. Lactic acidosis as a result of iron deficiency. J Clin Invest. 1979 Jul;64(1):129-37. doi: 10.1172/JCI109431.
- Results publication: PubMed 35046429Frise MC, Holdsworth DA, Johnson AW, Chung YJ, Curtis MK, Cox PJ, Clarke K, Tyler DJ, Roberts DJ, Ratcliffe PJ, Dorrington KL, Robbins PA. Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation. Sci Rep. 2022 Jan 19;12(1):998. doi: 10.1038/s41598-021-03968-4.
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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, DPhil study director
University of Oxford
Matthew C Frise, MRCP 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 Ferric carboxymaltose in people with Iron Deficiency, 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 4 inclusion and 9 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 19 Jul 2022. 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. 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?
Phosphocreatine depletion during small muscle mass exercise (time frame: 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)). 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 NCT02308449, which also lists 6 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 19 Jul 2022.