CardiomyopathyNCT02350829
T1 Mapping of Diffuse Myocardial Fibrosis in Congenital Heart Disease
A study testing Cardiac magnetic resonance sequence T1 mapping in people with Cardiomyopathy, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
Diffuse fibrosis (or scarring) of the heart muscle is found in a variety of congenital heart diseases and in cardiomyopathies (heart muscle disease), and is considered a mediator of decreased cardiac function. Read more about this study
- Who is it for?
- Ages 6 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiomyopathy
- What is being tested?
- Cardiac magnetic resonance sequence T1 mapping
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2014to Aug 2017
- 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 6 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Inclusion Criteria: Patients with cardiomyopathies (clinically established diagnosis of dilated or hypertrophic cardiomyopathy) / Patients with congenital heart disease (Diagnosis of Transposition of the great arteries after arterial switch operation, repaired Tetralogy of Fallot, patients after single ventricle palliation at the Fontan stage) scheduled for an MR investigation including gadolinium (MRI contrast medium)
- Patients / guardians capable of giving informed consent
- Informed written consent / assent by the parents / legal guardians and patients where applicable
- Ability to undergo a MRI examination without anaesthesia. Children > 6 years are typically able to cooperate sufficiently.
- Control Patients: Patients undergoing a non-cardiac MR investigation (musculoskeletal / abdomen / brain) including gadolinium without a history of cardiac disease
Exclusion Criteria:- Consent / assent refusal by guardian / patient
- General contraindications for a MRI examination such as non-MRI compatible metallic implants, claustrophobia.
- No contrast required for the clinical portion of the MRI
- Patients who require anaesthesia for MRI (typically < 6 years of age)
- Known renal failure or previous allergic reaction to gadolinium containing contrast agent
- Control subjects: history of cardiac problems, e.g. rhythm disorders, former myocarditis, active myositis or other inflammatory conditions except suspected or confirmed inflammatory bowel disease such as Crohn's disease or ulcerative colitis
- Known pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Quantification of Diffuse Myocardial Fibrosis in Children With Cardiomyopathy or Congenital Heart Disease by T1 Mapping Cardiac Magnetic Resonance
Diffuse fibrosis (or scarring) of the heart muscle is found in a variety of congenital heart diseases and in cardiomyopathies (heart muscle disease), and is considered a mediator of decreased cardiac function. The detection and quantification of diffuse myocardial fibrosis has recently become feasible non-invasively, using cardiac magnetic resonance (CMR), applying a new technique labeled T1 mapping. With this technique, the part of the heart tissue which is not made up of muscle cells (extracellular volume) can be quantified, as long as the individual's hematocrit (cellular volume in the blood) is known. The extracellular volume in the heart tissue is regarded as a quantifiable marker for the extent of diffuse myocardial fibrosis.
In the proposed study this new T1 mapping technique shall be applied in patients with different forms of congenital heart disease (n=130), cardiomyopathies (n=40) and in control subjects (n=30). The additional scan time due to participation in the study will be approximately 5-10 minutes, without changing the clinical protocol.
The main objective is to study the presence and extent of myocardial fibrosis by T1 mapping CMR in pediatric patients with congenital heart disease and cardiomyopathies, in comparison to cardiovascularly healthy controls.
Read the detailed description
A better understanding of the mechanisms by which the heart muscle fails in pediatric heart disease may result in novel therapies directed at preventing rather than treating ventricular failure. The most likely mediator candidate for cardiac demise in congenital heart disease as well as the cardiomyopathies is diffuse myocardial fibrosis and non-favorable chronic biventricular remodeling. As such, fibrosis may be a marker, if not a mediator, preceding the onset of actual echocardiographic and clinical deterioration, opening opportunities for more timely and targeted treatment. Chronic stressors of myocardial function (hypoxemia, abnormal afterload or preload) appear to promote fibrosis. In some groups of patients, a genetically upregulated collagen metabolism seems to play a role. In adult patients with dilated cardiomyopathy the extent of myocardial fibrosis is predictive of outcome.
With cardiac magnetic resonance imaging, the characterization of myocardial tissue is possible. Whereas standard late gadolinium enhancement (LGE) CMR can only identify patchy scars neighboring healthy tissue, quantification of diffuse myocardial fibrosis in the living has become feasible with the T1 mapping technique. Both techniques (T1 mapping and LGE) are based on the principle that MR contrast medium (gadolinium) is trapped in between collagen fibres and is retained in areas of fibrosis while it is quickly washed out of healthy myocardium. As gadolinium is a T1 shortening agent, the fibrosed tissue with its 'trapped' gadolinium has a shorter T1 time than healthy tissue. T1 mapping measures the T1 time constant, which has been shown to correlate with the degree of fibrosis. In a refined approach of this technique, which we will use, it is now possible to quantify the extracellular space (equivalent to the degree of fibrosis) by T1 mapping. This method has been validated against the current gold standard of surgical myocardial biopsy.
- Conditions
- Cardiomyopathy
- Being tested
- Cardiac magnetic resonance sequence T1 mapping
- Medical subject headings
- Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac magnetic resonance sequence T1 mappingOther
Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers
| Study group | Role | What they receive |
|---|---|---|
| Cardiomyopathy | Active comparator | Clinically established diagnosis of dilated, hypertrophic or arrhythmogenic right ventricular cardiomyopathy
Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Administering Multihance 0.2ml/kg as part of clinical scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers Receives: Other: Cardiac magnetic resonance sequence T1 mapping |
| Congenital Heart Disease | Active comparator | Diagnosis of Transposition of the great arteries after arterial switch operation, repaired Tetralogy of Fallot, patients after single ventricle palliation at the Fontan stage, native and repaired Aortic Coarctation Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Administering Multihance 0.2ml/kg as part of clinical scan
Obtaining bloodwork for assessment of hematocrit and collagen biomarkers Receives: Other: Cardiac magnetic resonance sequence T1 mapping |
| Controls | Active comparator | Patients undergoing a non-cardiac MR investigation (musculoskeletal / abdomen / brain) without a history of cardiac disease Adding limited cardiac sequence to the clinical magnetic resonance scan including T1 mapping Administering Multihance 0.2ml/kg as part of clinical scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers Receives: Other: Cardiac magnetic resonance sequence T1 mapping |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring degree of diffuse myocardial fibrosis
Participants will be followed for the duration of hospital visit, which is approximately 2 hours for the MRI part, and eventually longer, depending on possible other appointments on that day
Measured: Once at the end of the visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2015 (estimated)
- Study startFeb 2014
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CardiomyopathyStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lars Grosse-Wortmann, The Hospital for Sick Children
- Investigators
- Lars Grosse-Wortmann, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02350829
- Sponsor's protocol ID
- 1000039963
- Status last verified
- Sep 2019
- First submitted
- 20 Jan 2015
- Last updated
- 19 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of Diffuse Myocardial Fibrosis in Children With Cardiomyopathy or Congenital Heart Disease by T1 Mapping Cardiac Magnetic Resonance
- ClinicalTrials.gov ID
- NCT02350829
- Acronym / sponsor ID
- 1000039963
- Conditions
- Cardiomyopathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 30 Jan 2015 (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.
Diffuse fibrosis (or scarring) of the heart muscle is found in a variety of congenital heart diseases and in cardiomyopathies (heart muscle disease), and is considered a mediator of decreased cardiac function. The detection and quantification of diffuse myocardial fibrosis has recently become feasible non-invasively, using cardiac magnetic resonance (CMR), applying a new technique labeled T1 mapping. With this technique, the part of the heart tissue which is not made up of muscle cells (extracellular volume) can be quantified, as long as the individual's hematocrit (cellular volume in the blood) is known. The extracellular volume in the heart tissue is regarded as a quantifiable marker for the extent of diffuse myocardial fibrosis.
In the proposed study this new T1 mapping technique shall be applied in patients with different forms of congenital heart disease (n=130), cardiomyopathies (n=40) and in control subjects (n=30). The additional scan time due to participation in the study will be approximately 5-10 minutes, without changing the clinical protocol.
The main objective is to study the presence and extent of myocardial fibrosis by T1 mapping CMR in pediatric patients with congenital heart disease and cardiomyopathies, in comparison to cardiovascularly healthy controls.
Detailed description
A better understanding of the mechanisms by which the heart muscle fails in pediatric heart disease may result in novel therapies directed at preventing rather than treating ventricular failure. The most likely mediator candidate for cardiac demise in congenital heart disease as well as the cardiomyopathies is diffuse myocardial fibrosis and non-favorable chronic biventricular remodeling. As such, fibrosis may be a marker, if not a mediator, preceding the onset of actual echocardiographic and clinical deterioration, opening opportunities for more timely and targeted treatment. Chronic stressors of myocardial function (hypoxemia, abnormal afterload or preload) appear to promote fibrosis. In some groups of patients, a genetically upregulated collagen metabolism seems to play a role. In adult patients with dilated cardiomyopathy the extent of myocardial fibrosis is predictive of outcome.
With cardiac magnetic resonance imaging, the characterization of myocardial tissue is possible. Whereas standard late gadolinium enhancement (LGE) CMR can only identify patchy scars neighboring healthy tissue, quantification of diffuse myocardial fibrosis in the living has become feasible with the T1 mapping technique. Both techniques (T1 mapping and LGE) are based on the principle that MR contrast medium (gadolinium) is trapped in between collagen fibres and is retained in areas of fibrosis while it is quickly washed out of healthy myocardium. As gadolinium is a T1 shortening agent, the fibrosed tissue with its 'trapped' gadolinium has a shorter T1 time than healthy tissue. T1 mapping measures the T1 time constant, which has been shown to correlate with the degree of fibrosis. In a refined approach of this technique, which we will use, it is now possible to quantify the extracellular space (equivalent to the degree of fibrosis) by T1 mapping. This method has been validated against the current gold standard of surgical myocardial biopsy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cardiomyopathy | Active comparator | Other: Cardiac magnetic resonance sequence T1 mappingClinically established diagnosis of dilated, hypertrophic or arrhythmogenic right ventricular cardiomyopathy Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Administering Multihance 0.2ml/kg as part of clinical scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers |
| Congenital Heart Disease | Active comparator | Other: Cardiac magnetic resonance sequence T1 mappingDiagnosis of Transposition of the great arteries after arterial switch operation, repaired Tetralogy of Fallot, patients after single ventricle palliation at the Fontan stage, native and repaired Aortic Coarctation Adding T1 mapping sequence to the clinical cardiac magnetic resonance scan Administering Multihance 0.2ml/kg as part of clinical scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers |
| Controls | Active comparator | Other: Cardiac magnetic resonance sequence T1 mappingPatients undergoing a non-cardiac MR investigation (musculoskeletal / abdomen / brain) without a history of cardiac disease Adding limited cardiac sequence to the clinical magnetic resonance scan including T1 mapping Administering Multihance 0.2ml/kg as part of clinical scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
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 |
|---|---|---|
| Cardiac magnetic resonance sequence T1 mappingAdding T1 mapping sequence to the clinical cardiac magnetic resonance scan Obtaining bloodwork for assessment of hematocrit and collagen biomarkers | Other | Cardiomyopathy, Congenital Heart Disease, Controls |
Primary outcome
Measuring degree of diffuse myocardial fibrosis
Time frame: Once at the end of the visit
Participants will be followed for the duration of hospital visit, which is approximately 2 hours for the MRI part, and eventually longer, depending on possible other appointments on that day
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 Sep 2019.
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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.
Lars Grosse-Wortmann, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiac magnetic resonance sequence T1 mapping in people with Cardiomyopathy, run by The Hospital for Sick Children 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?
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 Sep 2019. 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?
Measuring degree of diffuse myocardial fibrosis (time frame: Once at the end of the visit). 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 19 Sep 2019.