Thalassemia MajorMAFIONCT02090699
MR Imaging of Diffuse Myocardial Fibrosis in Transfusion-Dependent Anemias
An observational study of Thalassemia Major and Chronic Blood Transfusion Related Iron Overload, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Cardiac failure is the major cause of death in patients with thalassemia and chronic blood transfusion-related iron overload. The treatment of thalassemia has been revolutionized over the past decade with the implementation of cardiac MRI based assessment of iron overload. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Thalassemia Major, Chronic Blood Transfusion Related Iron Overload
- How many people
- 42 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2013to Jun 2014
- Phase
- Observational
- 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
Study population: Patients with transfusion dependent anemias Age-matched healthy subjects
Who may be able to join
- Diagnosis of thalassemia Treatment with iron chelation therapy Referral for cardiac MR assessment of iron overload
- No significant past medical history and no evidence of cardiovascular or metabolic disease.
Who cannot join
- Arrhythmia Claustrophobia Pregnancy and potential pregnancy (patient cannot exclude potential pregnancy) History of allergic reaction to Gadolinium based contrast agent (GBCA) Impaired renal function with eGFR < 30 ml/min/1.73m2 Any general MR contraindication such as pacemaker or defibrillators.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Quantification of Diffuse Myocardial Iron Overload Related Interstitial Fibrosis With Cardiac Magnetic Resonance Imaging in Patients With Transfusion-Dependent Anemias
Cardiac failure is the major cause of death in patients with thalassemia and chronic blood transfusion-related iron overload. The treatment of thalassemia has been revolutionized over the past decade with the implementation of cardiac MRI based assessment of iron overload. This has enabled detection of cardiac iron overload prior to symptomatic heart failure and now allows for timely therapy which has resulted in a substantial decrease in mortality. However, currently implemented MR imaging techniques assess for iron content only and not for iron related diffuse fibrosis which play a role in iron related heart failure. Histopathologic studies indicate that patients with iron overload have diffuse interstitial fibrosis. Quantitative MR techniques have shown that patients with various cardiomyopathies demonstrate diffuse myocardial fibrosis and that these changes correlate with changes in cardiac function. The investigators propose that quantitative cardiac MRI for assessment of diffuse myocardial fibrosis can further improve our ability to detect early damage to the myocardium and prevent morbidity and mortality from cardiac iron overload. Detection of fibrosis in patients with thalassemia may allow for earlier identification of cardiomyopathy when compared to other techniques in clinical use including T2* analysis. Identification of fibrosis could affect patient management as it would allow for tailoring of iron chelation therapy and may lead to better understanding of the disease processes contributing to heart failure and arrhythmia in these patients.
Read the detailed description
Cardiac failure is the major cause of death in patients with transfusion-related iron overload. Histopathologic studies indicate that patients with myocardial siderosis have diffuse interstitial fibrosis. Cardiac MR assessment of the extracellular volume (ECV) fraction in other disease processes has been shown to accurately characterize diffuse myocardial fibrosis and to correlate with changes in diastolic function. No prior studies have assessed for diffuse interstitial myocardial fibrosis in patients with iron overload utilizing the proposed imaging techniques.
In this study, the investigators will assess the presence and extent of interstitial fibrosis in patients with transfusion-dependent anemias using cardiac MR techniques of T1 mapping and determination of ECV fraction. ECV values will be correlated with the severity of myocardial iron deposition determined by multi-echo T2*-weighted imaging, systolic ventricular function as determined by cardiac MR and diastolic function assessed by echocardiography. The investigators will recruit 35 patients with transfusion-related iron overload. Ten age-matched healthy subjects will be included as controls, to establish baseline values of myocardial T1 and ECV values. A modified Look-Locker with inversion recovery (MOLLI) sequence will be used to determine T1 values pre-, and post-administration of a gadolinium-based contrast agent (GBCA) at 1.5 Tesla. Calculated ECV values will be compared between iron-overload subjects and healthy controls, and will be correlated with left ventricular ejection fraction, measures of diastolic dysfunction and T2* values.
Detection of myocardial fibrosis in patients with iron overload would allow for improved prognostication and risk stratification. Elucidation of the relationship between myocardial fibrosis and myocardial iron deposition as well as cardiac functional parameters would provide valuable mechanistic insights and improved pathophysiological understanding of the disease. The results of the proposed study have the potential to significantly impact patient management including recommendations for earlier or more aggressive chelation therapy based on changes in ECV values.
- Keywords
- thalassemia major, chronic blood transfusion related iron overload, magnetic resonance imaging, myocardium, fibrosis
- Medical subject headings
- beta-Thalassemia, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Myocardial Iron Overload | chronic blood transfusion related myocardial iron overload | |
| Healthy Volunteers | age matched healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of diffuse myocardial fibrosis (elevated extracellular volume fraction) confirmed by MRI
At the time of MRI respective imaging data will be collected to assess the extracellular volume fraction as a marker for diffuse myocardial fibrosis.
Measured: at time of cardiac MR examination for each individual
Secondary outcomes (1)
Regional myocardial dysfunction as assessed by global longitudinal strain Echocardiography measurement
At the time of echocardiography (same day as MRI) respective strain data with be gathered for outcome assessment.
Measured: at time of echocardiography examination for each individual
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study startJul 2013
- Primary completionMay 2014
- Study completionJun 2014
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 Thalassemia MajorStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernd Winterspersper, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02090699
- Sponsor's protocol ID
- RSNA-RR1318
- Acronym
- MAFIO
- Status last verified
- Jul 2014
- First submitted
- 28 Feb 2014
- Last updated
- 17 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Hanneman K, Nguyen ET, Thavendiranathan P, Ward R, Greiser A, Jolly MP, Butany J, Yang IY, Sussman MS, Wintersperger BJ. Quantification of Myocardial Extracellular Volume Fraction with Cardiac MR Imaging in Thalassemia Major. Radiology. 2016 Jun;279(3):720-30. doi: 10.1148/radiol.2015150341. Epub 2015 Dec 10.
PubMed 26653680
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of Diffuse Myocardial Iron Overload Related Interstitial Fibrosis With Cardiac Magnetic Resonance Imaging in Patients With Transfusion-Dependent Anemias
- ClinicalTrials.gov ID
- NCT02090699
- Acronym / sponsor ID
- MAFIO / RSNA-RR1318
- Keywords
- thalassemia major, chronic blood transfusion related iron overload, magnetic resonance imaging, myocardium, fibrosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- May 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 18 Mar 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.
Cardiac failure is the major cause of death in patients with thalassemia and chronic blood transfusion-related iron overload. The treatment of thalassemia has been revolutionized over the past decade with the implementation of cardiac MRI based assessment of iron overload. This has enabled detection of cardiac iron overload prior to symptomatic heart failure and now allows for timely therapy which has resulted in a substantial decrease in mortality. However, currently implemented MR imaging techniques assess for iron content only and not for iron related diffuse fibrosis which play a role in iron related heart failure. Histopathologic studies indicate that patients with iron overload have diffuse interstitial fibrosis. Quantitative MR techniques have shown that patients with various cardiomyopathies demonstrate diffuse myocardial fibrosis and that these changes correlate with changes in cardiac function. The investigators propose that quantitative cardiac MRI for assessment of diffuse myocardial fibrosis can further improve our ability to detect early damage to the myocardium and prevent morbidity and mortality from cardiac iron overload. Detection of fibrosis in patients with thalassemia may allow for earlier identification of cardiomyopathy when compared to other techniques in clinical use including T2* analysis. Identification of fibrosis could affect patient management as it would allow for tailoring of iron chelation therapy and may lead to better understanding of the disease processes contributing to heart failure and arrhythmia in these patients.
Detailed description
Cardiac failure is the major cause of death in patients with transfusion-related iron overload. Histopathologic studies indicate that patients with myocardial siderosis have diffuse interstitial fibrosis. Cardiac MR assessment of the extracellular volume (ECV) fraction in other disease processes has been shown to accurately characterize diffuse myocardial fibrosis and to correlate with changes in diastolic function. No prior studies have assessed for diffuse interstitial myocardial fibrosis in patients with iron overload utilizing the proposed imaging techniques.
In this study, the investigators will assess the presence and extent of interstitial fibrosis in patients with transfusion-dependent anemias using cardiac MR techniques of T1 mapping and determination of ECV fraction. ECV values will be correlated with the severity of myocardial iron deposition determined by multi-echo T2*-weighted imaging, systolic ventricular function as determined by cardiac MR and diastolic function assessed by echocardiography. The investigators will recruit 35 patients with transfusion-related iron overload. Ten age-matched healthy subjects will be included as controls, to establish baseline values of myocardial T1 and ECV values. A modified Look-Locker with inversion recovery (MOLLI) sequence will be used to determine T1 values pre-, and post-administration of a gadolinium-based contrast agent (GBCA) at 1.5 Tesla. Calculated ECV values will be compared between iron-overload subjects and healthy controls, and will be correlated with left ventricular ejection fraction, measures of diastolic dysfunction and T2* values.
Detection of myocardial fibrosis in patients with iron overload would allow for improved prognostication and risk stratification. Elucidation of the relationship between myocardial fibrosis and myocardial iron deposition as well as cardiac functional parameters would provide valuable mechanistic insights and improved pathophysiological understanding of the disease. The results of the proposed study have the potential to significantly impact patient management including recommendations for earlier or more aggressive chelation therapy based on changes in ECV values.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Myocardial Iron Overload | – | –chronic blood transfusion related myocardial iron overload |
| Healthy Volunteers | – | –age matched healthy volunteers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with transfusion dependent anemias Age-matched healthy subjects
Key inclusion criteria (2 listed)
- Diagnosis of thalassemia Treatment with iron chelation therapy Referral for cardiac MR assessment of iron overload
- No significant past medical history and no evidence of cardiovascular or metabolic disease.
Key exclusion criteria (1 listed)
- Arrhythmia Claustrophobia Pregnancy and potential pregnancy (patient cannot exclude potential pregnancy) History of allergic reaction to Gadolinium based contrast agent (GBCA) Impaired renal function with eGFR < 30 ml/min/1.73m2 Any general MR contraindication such as pacemaker or defibrillators.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Evidence of diffuse myocardial fibrosis (elevated extracellular volume fraction) confirmed by MRI
Time frame: at time of cardiac MR examination for each individual
At the time of MRI respective imaging data will be collected to assess the extracellular volume fraction as a marker for diffuse myocardial fibrosis.
1 secondary outcome
Regional myocardial dysfunction as assessed by global longitudinal strain Echocardiography measurement
Time frame: at time of echocardiography examination for each individual
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 17 Jul 2014.
- Derived from this study: PubMed 26653680Hanneman K, Nguyen ET, Thavendiranathan P, Ward R, Greiser A, Jolly MP, Butany J, Yang IY, Sussman MS, Wintersperger BJ. Quantification of Myocardial Extracellular Volume Fraction with Cardiac MR Imaging in Thalassemia Major. Radiology. 2016 Jun;279(3):720-30. doi: 10.1148/radiol.2015150341. Epub 2015 Dec 10.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thalassemia Major and Chronic Blood Transfusion Related Iron Overload, run by University Health Network, Toronto at 1 site in Canada.
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 2 inclusion and 1 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 17 Jul 2014. 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 Canada. 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?
Evidence of diffuse myocardial fibrosis (elevated extracellular volume fraction) confirmed by MRI (time frame: at time of cardiac MR examination for each individual). 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 NCT02090699, 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 17 Jul 2014.