Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000950268
Ethics application status
Approved
Date submitted
3/11/2009
Date registered
4/11/2009
Date last updated
31/05/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of exercise training on cardiac autonomic function in patients with subclinical diabetic heart disease
Scientific title
Effects of exercise training on cardiac autonomic function in patients with subclinical diabetic heart disease
Secondary ID [1] 1115 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Cardiomyopathy 251993 0
Condition category
Condition code
Cardiovascular 252184 252184 0 0
Other cardiovascular diseases
Metabolic and Endocrine 252186 252186 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects (n=225) will be screened for subclinical diabetic heart disease. Patients with subclinical disease (based on evidence of diastolic dysfunction from non-invasive cardiac imaging) or autonomic neuropathy will then be allocated to exercise training (supervised gym-based sessions in addition to home-based training) for 6 months, or a control group. Exercise prescription (including intensity, duration and volume of exercise) will be based on the guidelines for exercise training for patients with type 2 diabetes defined by the American Heart Association and the American Diabetes Association. Eligibility for allocation will be determined by evidence of diastolic dysfunction based on tissue Doppler imaging echocardiographic parameters. In order to check for adverse events and compliance with treatment, subjects will receive follow-up phone calls.
Intervention code [1] 241403 0
Lifestyle
Comparator / control treatment
Subjects in the exercise training arm will be compared with matched subjects in a control arm.
Control group
Active

Outcomes
Primary outcome [1] 253062 0
Improvement in heart rate variability following exercise training.

Heart rate variability will be assessed by the coefficient of variation of R-R intervals recorded over 5 minutes using an electrocardiogram (ECG).
Timepoint [1] 253062 0
Patients will be tested for heart rate variability pre and post a 6-month exercise training intervention.
Primary outcome [2] 253088 0
Improvement in exercise capacity (maximal oxygen uptake - VO2max) following exercise training.
Timepoint [2] 253088 0
Patients will perform maximal treadmill exercise testing for maximal oxygen uptake (VO2max) pre and post a 6-month exercise training intervention.

Note: Heart rate variability and exercise capacity, comprising the two primary endpoints, will each be reported fully and with equal emphasis.
Secondary outcome [1] 257885 0
Improvement in early diastolic tissue velocity (Em) on tissue Doppler imaging echocardiography following exercise training.
Timepoint [1] 257885 0
Patients will be tested with echocardiography pre and post a 6-month exercise training intervention.
Secondary outcome [2] 257887 0
Improvement in glycaemic control following exercise training.
Timepoint [2] 257887 0
Patients will be tested for a blood biochemical marker of glycaemic control (glycosylated haemoglobin - HbA1c) pre and post a 6-month exercise training intervention.
Secondary outcome [3] 257888 0
Reduction in arterial stiffness following exercise training.
Timepoint [3] 257888 0
Patients will be tested for aortic stiffness (carotid-femoral pulse wave velocity) pre and post a 6-month exercise training intervention.
Secondary outcome [4] 257945 0
Documentation of change in early diastolic tissue velocity (Em) as an independent determinant of change in exercise capacity (VO2max) following 6 months exercise training.
Timepoint [4] 257945 0
This study will involve development of a model of determinants of change in exercise capacity (VO2max) pre and post a 6-month exercise training intervention. Change in Em will be forced into the model to ascertain whether it is an independent correlate of change in VO2max.
Secondary outcome [5] 257946 0
Documentation of change in heart rate variability as an independent determinant of change in early diastolic tissue velocity (Em) following 6 months exercise training.
Timepoint [5] 257946 0
This study will involve development of a model of determinants of change in early diastolic tissue velocity (Em) pre and post a 6-month exercise training intervention. Change in heart rate variability will be forced into the model to ascertain whether it is an independent correlate of change in Em.
Secondary outcome [6] 257947 0
Documentation of change in glycaemic control (HbA1c) as an independent determinant of change in heart rate variability following 6 months exercise training.
Timepoint [6] 257947 0
This study will involve development of a model of determinants of change heart rate variability pre and post a 6-month exercise training intervention. Change in HbA1c will be forced into the model to ascertain whether it is an independent correlate of change in heart rate variability.
Secondary outcome [7] 257948 0
Documentation of change in exercise capacity (VO2max) as an independent determinant of change in heart rate variability following 6 months exercise training.
Timepoint [7] 257948 0
This study will involve development of a model of determinants of change heart rate variability pre and post a 6-month exercise training intervention. Change in VO2max will be forced into the model to ascertain whether it is an independent correlate of change in heart rate variability.

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?
No
Key exclusion criteria
Known cardiovascular disease, pregnancy or breast-feeding, psychiatric illness precluding compliance, atrial fibrillation, other serious medical illness including renal impairment

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/02/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
225
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 243865 0
Government body
Name [1] 243865 0
NHMRC
Country [1] 243865 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
Southern Medical School
Princess Alexandra Hospital, Lvl 4 Bdg 1
199 Ipswich Road
Woolloogabba QLD 4102
Country
Australia
Secondary sponsor category [1] 237212 0
None
Name [1] 237212 0
Address [1] 237212 0
Country [1] 237212 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243988 0
Princess Alexandra Hospital Ethics Committee
Ethics committee address [1] 243988 0
Princess Alexandra Hospital
199 Ipswich Road
Woolloogabba QLD 4102
Ethics committee country [1] 243988 0
Australia
Date submitted for ethics approval [1] 243988 0
Approval date [1] 243988 0
05/06/2007
Ethics approval number [1] 243988 0
2007/85

Summary
Brief summary
This trial aims to determine the relationship between diabetic myocardial disease and cardiac autonomic neuropathy and the response of cardiac autonomic function to exercise training in patients demonstrating evidence of subclinical myocardial disease. The patient cohort will comprise apparently healthy patients with type 2 diabetes. Subjects with known cardiovascular disease or other significant co-morbidities such as malignancy, psychiatric or renal disease will be excluded. Pregnant or breast-feeding women will also be excluded. 225 patients will be recruited and undergo screening using echocardiography for diabetic heart disease. Based on past research conducted by our group, approximately one-third of patients will demonstrate evidence of subclinical myocardial dysfunction. Previous exercise training interventions have demonstrated significant improvements in maximal oxygen uptake (VO2max) in patient numbers of less than 30, so a proportionate improvement should be detectable from the study group even allowing for a 30% drop-out. There are no previous studies investigating cardiac autonomic function in diabetic patients with myocardial disease on which this study can be powered. Baseline measures on all subjects will include: body mass index, waist and hip circumference and resting haemodynamic parameters. Fasting blood samples will be collected to assess haematological parameters, renal and hepatic function, lipid profile, glucose, insulin, HbA1c, and B-type Natriuretic Peptide (BNP) concentrations. Urine collection for albumin to creatinine ratio for detection of diabetic nephropathy will also be performed. 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 re-imaged at peak heart rate for evidence of inducible wall motion abnormalities (indicative of ischaemic heart disease) and with 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. In addition to the echocardiography and exercise testing, patients will be studied for cardiac autonomic function using heart rate variability measured by electrocardiogram during supine rest. A standard 5-minute segment of R-R intervals will be analysed for both time and frequency domain parameters of heart rate variability. Patients will also undergo testing of cardiovascular reflexes (including heart rate responses to deep breathing, valsalva and standing and systolic blood pressure response to standing) to complete the battery of cardiac autonomic function tests. Patients with subclinical myocardial dysfunction or autonomic neuropathy will be allocated to exercise training (based on the current guidelines) or control for 6 months. Throughout the intervention, patients will receive 4-weekly follow-up to monitor for adverse events and compliance. Following the intervention, anthropometric, biochemical, autonomic, and imaging with rest and exercise echocardiograms will be repeated. Projected Outcomes: This trial aims to determine the efficacy of exercise training in diabetic cardiac autonomic neuropathy and subclinical myocardial disease. We hypothesise that exercise training will represent an effective treatment to improve exercise capacity and cardiac autonomic function, and that these improvements may represent mechanisms by which exercise training can improve myocardial function in patients with subclinical myocardial disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30380 0
Address 30380 0
Country 30380 0
Phone 30380 0
Fax 30380 0
Email 30380 0
Contact person for public queries
Name 13627 0
Julian Sacre
Address 13627 0
Southern School of Medicine
The University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Road
Woolloogabba QLD 4102
Country 13627 0
Australia
Phone 13627 0
+61 431 997 935
Fax 13627 0
Email 13627 0
j.sacre@uq.edu.au
Contact person for scientific queries
Name 4555 0
Julian Sacre
Address 4555 0
Southern School of Medicine
The University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Road
Woolloogabba QLD 4102
Country 4555 0
Australia
Phone 4555 0
+61 431 997 935
Fax 4555 0
Email 4555 0
j.sacre@uq.edu.au

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Results publications and other study-related documents

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