Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000789268
Ethics application status
Approved
Date submitted
23/06/2009
Date registered
10/09/2009
Date last updated
7/03/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Non-invasive cardiac imaging in the detection and assessment of subclinical diabetic heart disease
Scientific title
Non-invasive cardiac imaging in the detection and assessment of subclinical diabetic heart disease in type 2 diabetes mellitus patients - outcome of antifibrotic therapy with spironolactone
Secondary ID [1] 282083 0
No secondary ID
Universal Trial Number (UTN)
Trial acronym
No acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic cardiomyopathy 237082 0
Condition category
Condition code
Cardiovascular 237403 237403 0 0
Other cardiovascular diseases
Metabolic and Endocrine 237404 237404 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects (n=225) will be screened for evidence of diabetic heart disease. Subjects with either will then be matched to patients with diabetes but without these findings.
Patients with subclinical dysfunction will be randomized to spironolactone 1x25 mg tablet orally per day for 6 months (as an anti-fibrotic drug) or 1x placebo tablet orally per day for 6 months (lactose based tablet). Randomization will be stratified by evidence of diastolic dysfunction on tissue Doppler imaging echocardiographic parameters. After 6 months, patients will be free to take additional therapy for glycemic control. In order to check for adverse events and compliance with treatment, subjects will receive follow-up phone calls and electrolyte monitoring with blood tests at 4 week intervals.
Intervention code [1] 236801 0
Treatment: Drugs
Comparator / control treatment
Subjects in the spironolactone arm will be compared with matched subjects in the placebo arm.
Control group
Placebo

Outcomes
Primary outcome [1] 238207 0
Improvement in early diastolic tissue velocity on tissue Doppler imaging echocardiography following anti-fibrotic therapy with spironolactone
Timepoint [1] 238207 0
Patients will be screened with exhocardiography pre and post a 6 month intervention with spironolactone
Secondary outcome [1] 244520 0
Improvement in collagen biomarkers following anti-fibrotic therapy with spironolactone
Timepoint [1] 244520 0
Biomarkers will be measured pre and post a 6 month intervention with spironolactone
Secondary outcome [2] 257422 0
Improvement in deformation parameters on tissue Doppler imaging echocardiography following anti-fibrotic therapy with spironolactone
Timepoint [2] 257422 0
Patients will be screened with echocardiography pre and post a 6 month intervention with spironolactone
Secondary outcome [3] 257423 0
Improvement in diastolic functional class (on echocardiographic criteria) following anti-fibrotic therapy with spironolactone
Timepoint [3] 257423 0
Patients will be screened with echocardiography pre and post a 6 month intervention with spironolactone
Secondary outcome [4] 257424 0
Improvement of myocardial fibrosis on contrast enhanced magnetic resonance imaging (MRI) following anti-fibrotic therapy with spironolactone
Timepoint [4] 257424 0
Patients will be screened with magnetic resonance imaging (MRI) pre and post a 6 month intervention with spironolactone
Secondary outcome [5] 257425 0
Improvement in exercise capacity following anti-fibrotic therapy with spironolactone
Timepoint [5] 257425 0
Patients will be screened with treadmill exercise testing and maximal oxygen uptake pre and post a 6 month intervention with spironolactone

Eligibility
Key inclusion criteria
Type 2 diabetes mellitus
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Cardiac disease
Pregnancy or breast feeding
Psychiatric illness precluding compliance
Atrial Fibrillation (AF)
Other serious medical illness including renal impairment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
After suitability is confirmed by data entry, the database will generate an enrolment number and randomization statement via a central randomisation computer program with randomisation arm concealed from both the study investigators and the study subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation sequence is generated by random number generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/02/2009
Actual
16/02/2009
Date of last participant enrolment
Anticipated
31/12/2010
Actual
10/01/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
225
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 237195 0
Government body
Name [1] 237195 0
National health and Medical Research Council (NHMRC)
Country [1] 237195 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Southern Medical School
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Rd
Woolloongabba
QLD 4102
Country
Australia
Secondary sponsor category [1] 4690 0
None
Name [1] 4690 0
Address [1] 4690 0
Country [1] 4690 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239291 0
Princess Alexandra Hospital Ethics Committee
Ethics committee address [1] 239291 0
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
QLD 4102
Ethics committee country [1] 239291 0
Australia
Date submitted for ethics approval [1] 239291 0
Approval date [1] 239291 0
05/06/2007
Ethics approval number [1] 239291 0
2007/85

Summary
Brief summary
This project aims to establish the prevalence of subclinical diabetic heart disease, its relationship to myocardial fibrosis on imaging and biochemical parameters and its response to antifibrotic therapy with spironolactone.
MATERIALS & METHODS
Patient Selection
The patient cohort will compromise apparently healthy patients with type 2 diabetes mellitus (T2DM) and suboptimal control (glycosylated haemoglobin [HbA1c] > 7%) recruited from the hospital clinics and the community. Subjects with known macrovascular or microvascular complications of type two diabetes mellitus (T2DM), hypertensive, valvular or coronary disease or other significant co-morbidities such as arrhythmias, malignancy, psychiatric or renal disease will be excluded. Pregnant and breast feeding women will also be excluded.
Study design
225 patients will be recruited and undergo initial screening with echocardiography and cardiac magnetic resonance imaging for evidence of diabetic heart disease. Based on past studies at our research centre, it is predicted that approximately one third of these participants will have evidence of subclinical myocardial dysfunction. Previous work with spironolactone and hypertensive heart disease in our group has shown a significant impact on myocardial properties in patient numbers of less than 30, so a proportionate reduction should be detectable from this study group even allowing for a 30% drop-out. There are no previous studies investigating myocardial fibrosis in type 2 diabetes mellitus (T2DM) with cardiac magnetic resonance imaging on which this study can be powered.
Baseline measures on all subjects will include: body mass index, hip and waist circumference and resting haemodynamic parameters. Fasting blood samples will be collected to assess haematological parameters, renal and hepatic function, lipid profile, glucose, insulin, glycosylated haemoglobin (HbA1c) and brain natriuretic peptide (BNP) concentrations. Urine collection for albumin to creatinine ratio for detection of diabetic nephropathy will also be performed. Additional plasma, serum and urine will be stored for subsequent investigation of collagen biomarkers as surrogate measures of myocardial fibrosis.
All study subjects will undergo a baseline transthoracic echocardiogram to assess for evidence of systolic or diastolic dysfunction using standard echocardiographic parameters. Tissue Doppler imaging (TDI)including tissue velocity, strain and strain rate will be employed to detect further subclinical abnormalities. All subjects will then undergo a standard treadmill exercise stress test before being reimaged at peak heart rate for evidence of inducible wall motion abnormalities (indicative of ischaemic heart disease) and with tissue Doppler imaging (TDI) for subtle myocardial dysfunction which is not otherwise apparent at rest. Those with inducible wall motion abnormalities will be excluded based on their likelihood to have ischaemic heart disease. Appropriate clinical follow-up will be arranged.
Patients who are found to have evidence of subclinical myocardial dysfunction and a proportion of matched controls from the original patient group will then be further investigated with cardiac magnetic resonance imaging for evidence of underlying myocardial fibrosis. Patients with subclinical dysfunction will also be randomised to anti-fibrotic therapy with spironolactone (25 mg orally per day) or placebo for 6 months with the aim of reducing the extent and progression of myocardial collagen deposition. Throughout the intervention period, patients will receive 4 weekly follow-up to monitor for adverse events and compliance. Post-intervention, anthropometric measurements, biochemical markers and imaging with resting and exercise echocardiograms and cardiac magnetic resonance imaging will be repeated.
PROJECTED OUTCOMES
This work aims to highlight the importance of early detection and treatment of subclinical diabetic heart disease, which, if left unaddressed, may result in an epidemic of symptomatic diabetic heart disease in the future. We also hypothesize that anti-fibrotic therapy will have a favourable effect on myocardial function and exercise capacity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29788 0
Dr Christine Jellis
Address 29788 0
School of Medicine
The University of Queensland
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
4102, Qld
Country 29788 0
Australia
Phone 29788 0
+61 32405813
Fax 29788 0
Email 29788 0
c.jellis@uq.edu.au
Contact person for public queries
Name 13035 0
Dr Christine Jellis
Address 13035 0
Southern School of Medicine
University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Rd
Woolloongabba
QLD 4102
Country 13035 0
Australia
Phone 13035 0
+61 7 3240 5813
Fax 13035 0
+61 7 3240 5399
Email 13035 0
c.jellis@uq.edu.au
Contact person for scientific queries
Name 3963 0
Dr Christine Jellis
Address 3963 0
Southern School of Medicine
University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Rd
Woolloongabba
QLD 4102
Country 3963 0
Australia
Phone 3963 0
+61 7 3240 5813
Fax 3963 0
+61 7 3240 5399
Email 3963 0
c.jellis@uq.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIDiabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions2023https://doi.org/10.1038/s41420-023-01553-4
N.B. These documents automatically identified may not have been verified by the study sponsor.