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Trial registered on ANZCTR


Registration number
ACTRN12611000479909
Ethics application status
Approved
Date submitted
6/05/2011
Date registered
9/05/2011
Date last updated
15/05/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Multi-Parametric Cardiovascular Magnetic Resonance Assessment of Hypertrophic Cardiomyopathy
Scientific title
Multi-Parametric Cardiovascular Magnetic Resonance Assessment of Hypertrophic Cardiomyopathy
Secondary ID [1] 262125 0
None
Universal Trial Number (UTN)
U1111-1121-1965
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertrophic Cardiomyopathy 265798 0
Condition category
Condition code
Cardiovascular 265954 265954 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All phenotype positive patients will undergo a 10ml genetic blood test. Patients who are then genotype positive for cardiac myosin binding protein-C mutations or cardiac beta-myosin heavy chain gene mutations will be recruited and undergo baseline cardiac magnetic resonance imaging, cardiac magnetic resonance spectroscopy and echocardiography. These will be repeated at 1, 2 and 4 years.
Intervention code [1] 264539 0
Not applicable
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 266706 0
Phosphocreatine (PCr)/Adenosinetriphosphate (ATP) ratio. Method: Cardiac magnetic resonance spectroscopy will be used to measure cardiac high energy phosphate metabolism in-vivo. The novel SLOOP method (spatial localisation with optimum pointspread function) allows accurate measurement of absolute concentrations of high-energy phosphates.
Timepoint [1] 266706 0
4 years for the main study.
Secondary outcome [1] 276226 0
AMPK activity as measured by peripheral blood test
Timepoint [1] 276226 0
4 years for the main study.
Secondary outcome [2] 276237 0
Absolute concentration of high-energy phosphates as measured by cardiac magnetic spectroscopy.
Timepoint [2] 276237 0
4 years for the main study.
Secondary outcome [3] 276238 0
LV diastolic function as measured by cardiac magnetic resonance imaging and doppler echocardiography
Timepoint [3] 276238 0
4 years for the main study.
Secondary outcome [4] 276239 0
regional function as measured by cardiac magnetic resonance imaging
Timepoint [4] 276239 0
4 years for the main study.
Secondary outcome [5] 276240 0
LV systolic function as measured by cardiac magnetic resonance imaging
Timepoint [5] 276240 0
4 years for the main study.

Eligibility
Key inclusion criteria
Hypertrophic cardiomyopathy patients aged between 18 and 75; phenotype positive (established by echocardiography or cardiac magnetic resonance scan); genotype positive for cardiac myosin binding protein-C gene mutations or cardiac beta-myosin heavy chain gene mutations.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Impaired LV systolic function (EF <50%) as detected on echocardiography or cardiac magnetic resonance scan; history of diabetes mellitus, calculated GFR <30mls/hr; significant derranged liver function defined as liver enzymes of 3 x ULN; current therapy with metformin or amiodarone; absolute contraindication of having MRI scan.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3997 0
5042

Funding & Sponsors
Funding source category [1] 265025 0
Charities/Societies/Foundations
Name [1] 265025 0
National Heart Foundation
Address [1] 265025 0
Heart Foundation
Research Program
Level 12, 500 Collins Street,
Melbourne VIC 3000,
Australia
Country [1] 265025 0
Australia
Primary sponsor type
Individual
Name
Professor Joseph Selvanayagam
Address
Department of Cardiovascular Medicine
Flinders Medical Centre
1 Flinders Drive
BEDFORD PARK SA 5042
Country
Australia
Secondary sponsor category [1] 264121 0
Individual
Name [1] 264121 0
Professor John Horowitz
Address [1] 264121 0
Department of Cardiology
The Queen Elizabeth Hospital
Woodville South, Adelaide
South Australia 5011
Country [1] 264121 0
Australia
Secondary sponsor category [2] 264122 0
Individual
Name [2] 264122 0
Professor Christopher Semsarian
Address [2] 264122 0
Molecular Cardiology, Centenary Institute
Royal Prince Alfred Hospital
Missenden Rd
Camperdown, NSW 2050
Country [2] 264122 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 267008 0
Flinders Clinical Research Ethics Committee
Ethics committee address [1] 267008 0
Flinders Medical Centre
Flinders Drive
BEDFORD PARK SA 5042
Ethics committee country [1] 267008 0
Australia
Date submitted for ethics approval [1] 267008 0
09/09/2010
Approval date [1] 267008 0
17/12/2010
Ethics approval number [1] 267008 0
36910

Summary
Brief summary
Hypertrophic cardiomyopathy (HCM) is the most common cardiovascular genetic disorder and can cause significant morbidity and mortality, including the most serious complications of heart failure and sudden death. At present, there are no proven pharmacological therapies that either prevent or cause regression of clinical features. This is largely due to a lack of knowledge in our understanding of the molecular and functional consequences of the disease-causing gene mutations leading to the clinical disease. The proposed study will aim to test whether cardiac energetic compromise is a central pathophysiological mechanism in HCM. We will investigate potentially beneficial treatments based on our hypothesis of trialling the use of metformin in a HCM group. If the results from this ‘proof of concept study’ are confirmatory, it could pave the way for larger multi-centre randomised studies (with longer duration of treatment) with either metformin or facilitators of fatty acid oxidation such as ranolazine. If realised, these treatments could prevent the vicious cycle of cardiac hypertrophy and myocardial dysfunction seen in HCM, leading to improved morbidity and mortality. These investigations will establish early phenotype changes in HCM patients and provide insights into potential therapeutic interventions for a condition that currently has little therapeutic evidence base.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32577 0
Address 32577 0
Country 32577 0
Phone 32577 0
Fax 32577 0
Email 32577 0
Contact person for public queries
Name 15824 0
Christine Edwards
Address 15824 0
Flinders Clinical Research
Level 3A
Mark Oliphant Building
Laffer Drive
BEDFORD PARK SA 5042
Country 15824 0
Australia
Phone 15824 0
+61 8 8204 5656
Fax 15824 0
+61 8 8204 7047
Email 15824 0
christine.edwards2@health.sa.gov.au
Contact person for scientific queries
Name 6752 0
Professor Joseph Selvanayagam
Address 6752 0
Department of Cardiovascular Medicine
Flinders Medical Centre
1 Flinders Drive
BEDFORD PARK SA 5042
Country 6752 0
Australia
Phone 6752 0
+61 8 8404 2195
Fax 6752 0
Email 6752 0
joseph.selvanayagam@health.sa.gov.au

No information has been provided regarding IPD availability
Summary results
No Results