ANZCTR - Registration

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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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Diabetic Cardiomyopathy

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Metabolic and Endocrine

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]

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]

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]

Patients will be tested for heart rate variability pre and post a 6-month exercise training intervention.

Primary outcome [2]

Improvement in exercise capacity (maximal oxygen uptake - VO2max) following exercise training.

Timepoint [2]

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]

Improvement in early diastolic tissue velocity (Em) on tissue Doppler imaging echocardiography following exercise training.

Timepoint [1]

Patients will be tested with echocardiography pre and post a 6-month exercise training intervention.

Secondary outcome [2]

Improvement in glycaemic control following exercise training.

Timepoint [2]

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]

Reduction in arterial stiffness following exercise training.

Timepoint [3]

Patients will be tested for aortic stiffness (carotid-femoral pulse wave velocity) pre and post a 6-month exercise training intervention.

Secondary outcome [4]

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]

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]

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]

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]

Documentation of change in glycaemic control (HbA1c) as an independent determinant of change in heart rate variability following 6 months exercise training.

Timepoint [6]

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]

Documentation of change in exercise capacity (VO2max) as an independent determinant of change in heart rate variability following 6 months exercise training.

Timepoint [7]

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?

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]

Government body

Name [1]

NHMRC

Address [1]

National Health and Medical Research Council
National Institute of Clinical Studies
GPO BOX 4530
Melbourne VIC 3001

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Princess Alexandra Hospital Ethics Committee

Ethics committee address [1]

Princess Alexandra Hospital
199 Ipswich Road
Woolloogabba QLD 4102

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

05/06/2007

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Julian Sacre

Address

Southern School of Medicine
The University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Road
Woolloogabba QLD 4102

Country

Australia

Phone

+61 431 997 935

Fax

[email protected]

Contact person for scientific queries

Name

Julian Sacre

Address

Southern School of Medicine
The University of Queensland
Princess Alexandra Hospital
Level 4 Building 1
199 Ipswich Road
Woolloogabba QLD 4102

Country

Australia

Phone

+61 431 997 935

Fax

[email protected]

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

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically