Iron-deficiencyMitoCardioFerNCT03541213
Impact of Iron Deficiency and Its Correction on Mitochondrial Metabolism of the Cardiomyocyte (MitoCardioFer)
A study testing myocardial biopsy, sternal bone marrow biopsy and blood sample in people with Iron-deficiency and Valvular Heart Disease, run by University Hospital, Angers at 1 site in France.
Trial summary
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Iron-deficiency, Valvular Heart Disease
- What is being tested?
- myocardial biopsy, sternal bone marrow biopsy and blood sample
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteFrance
- Study dates
- 23 Jan 2019to 7 Sep 2020
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Patients that must be operated for a valvular heart surgery (aortic or mitral) scheduled in the month which follows the anaesthesia consultation (visit of inclusion)
- The preoperative iron status is known
- Patient signed informed consent
Who cannot join
- Refusal of the patient to participate
- Refusal of the surgeon or the anaesthetist who are responsible of patient management
- Patients with a known iron overload (for example : hemochromatosis)
- Counter-indication in the realization of a sternal bone marrow biopsy or myocardial biopsy (for example : endocarditis)
- Adult patients under legal guardianship
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact de la Carence Martiale et de Son Traitement Sur le métabolisme Mitochondrial du Cardiomyocyte (MitoCardioFer)
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients. Iron therapy improves symptoms and physical performances of heart failure patients, even in the absence of anemia. As a result, the correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
Read more
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
Read the detailed description
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Iron deficiency has been shown to be responsible for fatigue and muscle weakness, regardless of the presence of an anemia. Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients, with a prevalence increasing with NYHA class level, and association with mortality. Iron therapy improves the symptoms of heart failure patients and the 6-minute walk test, even in the absence of anemia. The correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient. There is therefore an opportunity to further explore the impact of iron deficiency and its treatment on mitochondrial energy metabolism of cardiomyocytes. We hypothesize that the activity of the mitochondrial complex I is decreased in the presence of iron deficiency and that the iron treatment corrects this decrease.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
- Conditions
- Iron-deficiency, Valvular Heart Disease
- Being tested
- myocardial biopsy, sternal bone marrow biopsy, blood sample
- Keywords
- ferric carboxymaltose, mitochondrial metabolism, cardiomyocyte
- Medical subject headings
- Anemia, Iron-Deficiency, Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
myocardial biopsyProcedure or surgery
Myocardial biopsy (after opening cardiac cavities under general anesthesia for valvular surgery) for mitochondrial metabolism analyses.
sternal bone marrow biopsyProcedure or surgery
Sternal bone marrow biopsy (after sternal opening under general anesthesia for valvular surgery) for the quantification of iron stores
blood sampleBiological
blood sample (under general anesthesia for valvular surgery, using the arterial catheter already in place) for hepcidin quantification (hormone not dosed in the usual martial assessment)
| Study group | Role | What they receive |
|---|---|---|
| Control group | Other | Patients with no iron deficiency prior to inclusion and who did not receive intravenous iron prior to inclusion.
Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) Receives: Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample |
| Iron deficiency group | Other | Patients with iron deficiency who did not receive intravenous iron prior to inclusion.
Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) Receives: Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample |
| Iron treated group | Other | Patients with iron deficiency who received intravenous iron prior to inclusion (greater than or equal to 1 g ferric carboxymaltose).
Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) Receives: Procedure: myocardial biopsy; Procedure: sternal bone marrow biopsy; Biological: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure of the maximal activity of the mitochondrial complex I using spectrometry
Measure of the maximal complex I activity using spectrometry on isolated mitochondria from myocardial biopsy.
Measured: At the time of the myocardial biopsy
Secondary outcomes (5)
Measure of the maximal activity of the others mitochondrial complexes using spectrometry (Complexes II, III and IV)
Measured: At the time of the myocardial biopsy
Quantification of the number of mitochondria per cardiomyocyte using Western-Blot
Measured: At the time of the myocardial biopsy
Quantification and analysis of the complex I assemblage using BN-PAGE
Measured: At the time of the myocardial biopsy
Quantification of myoglobin in cardiomyocytes using Western-Blot
Measured: At the time of the myocardial biopsy
Cardiac function using echocardiography in pre-, intra- and post-operative periods
Measured: At the time of the myocardial biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start23 Jan 2019
- Primary completion7 Sep 2020
- Study completion7 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron-deficiencyStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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
- Single group
- Model description
- 3 groups will be performed depending on the presence or absence of a pre-operative iron deficiency and whether they had an iron treatment preoperatively (before their inclusion in the study). However, patient management will not be different in the different groups from their inclusion in the study. Therefore we can consider that there is a single interventional group.
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- RINEAU Emmanuel, MD, Principal investigator, University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03541213
- Sponsor's protocol ID
- 2017-A00904-49
- Acronym
- MitoCardioFer
- Status last verified
- Jul 2022
- First submitted
- 17 May 2018
- Last updated
- 29 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact de la Carence Martiale et de Son Traitement Sur le métabolisme Mitochondrial du Cardiomyocyte (MitoCardioFer)
- ClinicalTrials.gov ID
- NCT03541213
- Acronym / sponsor ID
- MitoCardioFer / 2017-A00904-49
- Conditions
- Iron-deficiency, Valvular Heart Disease
- Keywords
- ferric carboxymaltose, mitochondrial metabolism, cardiomyocyte
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 23 Jan 2019 (actual)
- Primary completion
- 7 Sep 2020 (actual)
- Study completion
- 7 Sep 2020 (actual)
- First posted
- 30 May 2018 (actual)
- 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 is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients. Iron therapy improves symptoms and physical performances of heart failure patients, even in the absence of anemia. As a result, the correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
Detailed description
Iron is involved in essential functions of the body. It allows the transport of oxygen in the blood, via hemoglobin, at the muscular level, via myoglobin, and it is also involved in cellular metabolism in general, in particular for the production of ATP at the mitochondrial level, within the cytochromes and iron-sulfur proteins of the respiratory chain.
Iron deficiency has been shown to be responsible for fatigue and muscle weakness, regardless of the presence of an anemia. Recently, iron deficiency has been identified as an important prognostic factor in heart failure patients, with a prevalence increasing with NYHA class level, and association with mortality. Iron therapy improves the symptoms of heart failure patients and the 6-minute walk test, even in the absence of anemia. The correction of iron deficiency is now proposed as one of the therapies for heart failure. However, the pathophysiology of the association between cardiac dysfunction and iron deficiency is still poorly understood.
The investigators previously developed a mouse model of iron deficiency without anemia, in which the investigators observed impaired physical performances, a decrease of left ventricular ejection fraction, and a decrease in mitochondrial complex I activity. These abnormalities were normalized after iron injection. These animal data suggest that iron deficiency is responsible for left ventricular dysfunction secondary to mitochondrial I complex abnormalities, and that iron therapy corrects them.
Iron deficiency is very common in the preoperative period of cardiac surgery, affecting 40 to 50% of patients. During this surgery, it is possible to perform a myocardial biopsy without risk to the patient. There is therefore an opportunity to further explore the impact of iron deficiency and its treatment on mitochondrial energy metabolism of cardiomyocytes. We hypothesize that the activity of the mitochondrial complex I is decreased in the presence of iron deficiency and that the iron treatment corrects this decrease.
The purpose of this study is to verify in patients requiring valvular heart surgery, if iron deficiency is responsible for a decrease in mitochondrial complex I activity and a decrease in cardiac function during the perioperative period, and to verify whether iron treatment improves these abnormalities.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 3 groups will be performed depending on the presence or absence of a pre-operative iron deficiency and whether they had an iron treatment preoperatively (before their inclusion in the study). However, patient management will not be different in the different groups from their inclusion in the study. Therefore we can consider that there is a single interventional group.
| Arm | Type | Receives |
|---|---|---|
| Control group | Other | Procedure: myocardial biopsy, Procedure: sternal bone marrow biopsy, Biological: blood samplePatients with no iron deficiency prior to inclusion and who did not receive intravenous iron prior to inclusion. Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) |
| Iron deficiency group | Other | Procedure: myocardial biopsy, Procedure: sternal bone marrow biopsy, Biological: blood samplePatients with iron deficiency who did not receive intravenous iron prior to inclusion. Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) |
| Iron treated group | Other | Procedure: myocardial biopsy, Procedure: sternal bone marrow biopsy, Biological: blood samplePatients with iron deficiency who received intravenous iron prior to inclusion (greater than or equal to 1 g ferric carboxymaltose). Intervention : myocardial biopsy, sternal bone marrow biopsy and blood sample (as in the other arms) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Patients that must be operated for a valvular heart surgery (aortic or mitral) scheduled in the month which follows the anaesthesia consultation (visit of inclusion)
- The preoperative iron status is known
- Patient signed informed consent
Key exclusion criteria (6 listed)
- Refusal of the patient to participate
- Refusal of the surgeon or the anaesthetist who are responsible of patient management
- Patients with a known iron overload (for example : hemochromatosis)
- Counter-indication in the realization of a sternal bone marrow biopsy or myocardial biopsy (for example : endocarditis)
- Adult patients under legal guardianship
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 |
|---|---|---|
| myocardial biopsyMyocardial biopsy (after opening cardiac cavities under general anesthesia for valvular surgery) for mitochondrial metabolism analyses. | Procedure or surgery | Control group, Iron deficiency group, Iron treated group |
| sternal bone marrow biopsySternal bone marrow biopsy (after sternal opening under general anesthesia for valvular surgery) for the quantification of iron stores | Procedure or surgery | Control group, Iron deficiency group, Iron treated group |
| blood sampleblood sample (under general anesthesia for valvular surgery, using the arterial catheter already in place) for hepcidin quantification (hormone not dosed in the usual martial assessment) | Biological | Control group, Iron deficiency group, Iron treated group |
Primary outcome
Measure of the maximal activity of the mitochondrial complex I using spectrometry
Time frame: At the time of the myocardial biopsy
Measure of the maximal complex I activity using spectrometry on isolated mitochondria from myocardial biopsy.
5 secondary outcomes
Measure of the maximal activity of the others mitochondrial complexes using spectrometry (Complexes II, III and IV)
Time frame: At the time of the myocardial biopsy
Quantification of the number of mitochondria per cardiomyocyte using Western-Blot
Time frame: At the time of the myocardial biopsy
Quantification and analysis of the complex I assemblage using BN-PAGE
Time frame: At the time of the myocardial biopsy
Quantification of myoglobin in cardiomyocytes using Western-Blot
Time frame: At the time of the myocardial biopsy
Cardiac function using echocardiography in pre-, intra- and post-operative periods
Time frame: At the time of the myocardial biopsy
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 29 Jul 2022.
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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.
RINEAU Emmanuel, MD principal investigator
University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing myocardial biopsy, sternal bone marrow biopsy and blood sample in people with Iron-deficiency and Valvular Heart Disease, run by University Hospital, Angers at 1 site in France.
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 6 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 29 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 France. 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?
Measure of the maximal activity of the mitochondrial complex I using spectrometry (time frame: At the time of the myocardial biopsy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2022.