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Trial registered on ANZCTR


Registration number
ACTRN12615001292561
Ethics application status
Approved
Date submitted
23/11/2015
Date registered
26/11/2015
Date last updated
12/03/2019
Date data sharing statement initially provided
12/03/2019
Date results information initially provided
12/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility, safety, adherence, and efficacy of high intensity interval training in a hospital-initiated rehabilitation program for heart disease.
Scientific title
Feasibility, safety, adherence, and efficacy of high intensity interval training compared to moderate intensity continuous training in a hospital-initiated cardiac rehabilitation program for patients with coronary artery disease.
Secondary ID [1] 287947 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The FITR Heart Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary artery disease 296828 0
Condition category
Condition code
Cardiovascular 297054 297054 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High intensity interval training
Isocaloric exercise protocol to usual care
31 minutes exercise (including 3minute warm-up and 3 minute cool down)
- Following warm-up, 4 x 4minute high intensity intervals (85-95% VO2 peak)
- Interspersed with 3minute intervals (3 in total) of moderate intensity intervals (60-70% VO2 peak)
Various aerobic exercise machines will be used, depending on preference and musculoskeletal limitations. These include treadmill, cycle ergometer, cross-trainer, or rowing ergometer. Training will be adapted for home-based exercise equipment or walking program.

Stage 1: Four weeks hospital program = 2 x supervised sessions and 1 home-based session per week. All supervised classes will be delivered by an Accredited Exercise Physiologist.
Stage 2: Eight weeks home-based program (3 sessions/week) with weekly telephone support These weekly 5-10 minute calls will be provided by a qualified health professional (e.g. nurse or exercise physiologist) to discuss adherence and other issues (e.g. symptoms).
Stage 3: Maintain home-based program (at least 3 sessions/week) for a further 9 months. Follow-up testing at 6 months and 12 months from baseline measures.

Adherence to exercise program will be monitored at supervised rehabilitation sessions (initial 4 weeks), home exercise log with weekly telephone follow-up (for subsequent 8 weeks), FitBit device data (for a sub-group of patients), and 7-day accelerometer data at each testing period (4 weeks, 13 weeks, 6 months, 12 months).

Compliance will be assessed as 70% adherence to recommended exercise program (intensity, type, time, and frequency)

Dietary control will also be monitored on 2 days at each testing period by a dietitian administered 24-hour recall.
Intervention code [1] 293292 0
Rehabilitation
Intervention code [2] 293293 0
Lifestyle
Intervention code [3] 293317 0
Prevention
Comparator / control treatment
Moderate intensity continuous training (usual care)
40 minutes exercise (including 3 minute warm-up and 3 minute cool down)
Intensity of 11-13 (fairly light to somewhat hard) based on BORG rating of perceived exertion (RPE) 6-20 scale

Various aerobic exercise machines will be used, depending on preference and musculoskeletal limitations. These include treadmill, cycle ergometer, cross-trainer, or rowing ergometer. Training will be adapted for home-based exercise equipment or walking program.

Stage 1: Four weeks hospital program = 2 x supervised sessions and 1 home-based session per week. All supervised classes will be delivered by an Accredited Exercise Physiologist.
Stage 2: Eight weeks home-based program (3 sessions/week) with weekly telephone support These weekly 5-10 minute calls will be provided by a qualified health professional (e.g. nurse or exercise physiologist) to discuss adherence and other issues (e.g. symptoms).
Stage 3: Maintain home-based program (at least 3 sessions/week) for a further 9 months. Follow-up testing at 6 months and 12 months from baseline measures.

Adherence to exercise program will be monitored at supervised rehabilitation sessions (initial 4 weeks), home exercise log with weekly telephone follow-up (for subsequent 8 weeks), FitBit device data (for a sub-group of patients), and 7-day accelerometer data at each testing period (4 weeks, 13 weeks, 6 months, 12 months).

Compliance will be assessed as 70% adherence to recommended exercise program (intensity, type, time, and frequency)

Dietary control will also be monitored on 2 days at each testing period by a dietitian administered 24-hour recall.
Control group
Active

Outcomes
Primary outcome [1] 296657 0
Cardiorespiratory fitness as peak oxygen consumption (VO2 peak), measured by maximal exercise test.
Timepoint [1] 296657 0
4 weeks
Primary outcome [2] 296658 0
Visceral adipose tissue volume, captured by magnetic resonance imaging and quantified using automated specialised software.
Timepoint [2] 296658 0
4 weeks.
Secondary outcome [1] 319020 0
Body composition (total body lean tissue mass, fat mass, bone mineral density, and visceral adipose tissue) measured by dual-energy x-ray absorptiometry.
Timepoint [1] 319020 0
4 weeks, 13 weeks, 6 months, and 12 months
Secondary outcome [2] 319021 0
Cardiorespiratory fitness as peak oxygen consumption (VO2 peak), measured by maximal exercise test.
Timepoint [2] 319021 0
Repeated measures at 13 weeks, 6 months, and 12 months.
Secondary outcome [3] 319023 0
Cardiovascular disease risk factors such as body weight, waist circumference, blood pressure, total cholesterol, LDL:HDL cholesterol ratio, triglycerides, and insulin resistance.

Blood samples will be collected to measure lipid profile and insulin resistance. Total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) will be assessed using cholesterol lipid assay kits. Detection and quantification of plasma insulin will be performed using a radioimmunoassay kit. The homeostasis assessment model (HOMA) will be used to estimate insulin resistance.

Blood pressure will be measured by sphygmomanometry on each arm after 10 minutes of quiet sitting, with a second reading on each arm taken. When there is a difference >10 mmHg between arms the highest reading recorded will be taken.
Timepoint [3] 319023 0
4 weeks, 13 weeks, 6 months, and 12 months
Secondary outcome [4] 319024 0
Vascular function measured as flow-mediated dilation (by brachial artery reactivity).
Timepoint [4] 319024 0
4 weeks, 13 weeks, 6 months, and 12 months
Secondary outcome [5] 319025 0
Safety will be measured by data collected on adverse events.

Participants will be advised that they should report any spontaneous adverse events that may occur during the study, and will be provided with contact details for reporting.
During Stage 1 and Stage 2 participants will be questioned weekly about adverse events at supervised sessions or by weekly telephone support. During Stage 3 participants will be questioned at the 6 month and 12 month follow-up.
Participants will be encouraged to use the contact details for reporting adverse events at any time throughout the study period. The type, incidence, and severity of adverse events (Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; and Grade 5: Death) will be noted. Examples of adverse effects would be musculoskeletal injury, angina, hypotension, myocardial infarction).

Timepoint [5] 319025 0
Data will be collected on a continual basis.
Data will be analysed at 4 weeks, 13 weeks, 6 months, and 12 months. Data will be collected
Secondary outcome [6] 319026 0
Exercise adherence will be assessed as 70% compliance to the prescribed type, frequency, intensity, and duration of exercise sessions/week.

A combination of physical attendence, self-reporting, and activity device data (accelerometer) will be used. The participant will be deemed compliant if they achieve 70% of the randomized exercise protocol targets each week.

During Stage 1, exercise adherence will be recorded on the exercise data sheets at supervised exercise sessions. At each exercise session, participants will be asked if they have completed any home-based sessions since their previous supervised sessions, and the nature of this session.
During Stage 2, exercise adherence will be self-reported by participants during their routine telephone support session. They will be asked how many sessions they have completed for the week, and the duration and intensity of those sessions. During the supervised sessions participants will be taught how to monitor their exercise intensity using heart rate and rating of perceived effort (RPE). They will be encouraged to keep an exercise log to track this data for their home-based sessions. For those participants using Fit-Bits, uploaded data will also be used to assess compliance to the duration, frequency, and intensity of exercise sessions.
During Stage 3, exercise adherence will be self-reported by participants during their 6 month and 12 month follow-up sessions. Accelerometer data, captured for 7 days at each testing period, will also be used to assess compliance to the exercise protocol.
Timepoint [6] 319026 0
4 weeks, 13 weeks, 6 months, and 12 months
Secondary outcome [7] 319027 0
Feasibility measured by cardiac rehabilitation staff exercise training feedback questionnaire and participant exercise training feedback questionnaire. These questionnaires have been specifically designed for this study. Face validation of these questionnaires has been provided by a clinical psychologist within the Centre of Research for Exercise, Physical Activity, and Health (The University of Queensland)
Timepoint [7] 319027 0
4 weeks, 13 weeks, 6 months, and 12 months
Secondary outcome [8] 319028 0
Patient quality of life measured by The McNew Heart Disease health-related quality of life instrument
Timepoint [8] 319028 0
4 week, 13 weeks, 6 months, and 12 months.
Secondary outcome [9] 319029 0
Intrahepatic lipid (liver fat) measured by proton magnetic resonance spectroscopy during magnetic resonance imaging procedure.
Timepoint [9] 319029 0
4 weeks and 13 weeks.
Secondary outcome [10] 319131 0
Vascular structure measured as arterial stiffness (by pulse wave velocity)
Timepoint [10] 319131 0
4 weeks, 13 weeks, 6 months, and 12 months.
Secondary outcome [11] 321707 0
Dietary intake, behaviour and food preferences measured by 24hr recall multi pass method, Three Factor Eating Questionnaire, and computer-based Leeds Food Preference Questionnaire.
Timepoint [11] 321707 0
4 weeks, 13 weeks, 6 months, and 12 months

Eligibility
Key inclusion criteria
Coronary artery disease patients who are eligible to attend the Wesley Hospital Phase II cardiac rehabilitation program will be offered the opportunity to participate in the study. Diagnostic criteria for coronary artery disease is confirmation of the disease in at least one vessel by a cardiologist following coronary angiogram. Patients may have a history of myocardial infarction (MI) > 4 weeks, percutaneous coronary intervention (PCI) > 3 weeks, coronary artery bypass graft (CABG) surgery > 4 weeks, valve surgery > 4 weeks, and heart failure. Access to a smartphone or computer will also be required.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Absolute or relative contraindications to exercise testing as per American College of Cardiology and American Heart Association guidelines, including but not limited to:
Unstable angina; Unstable arrhythmias, Significant valvular disease; Uncompensated heart failure; Pulmonary disease; Uncontrolled hypertension (systolic blood pressure > 200 mmHg and/or diastolic blood pressure >110 mmHg); Renal failure (Chronic Kidney Disease stages III-V); Orthopaedic/neurological limitations; Physical impairment limiting the ability to exercise.

Additionally patients will be excluded for: Planned operations during the research period; Drug or alcohol abuse; Planning to or participation in another study; Not willing to sign the consent from; Females pregnant or expecting to be pregnant during the study period; Any other reason which would limit their ability to participate in this study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The sample size calculation for peak VO2 was conducted using the change over the four week supervised phase of the CR program, the primary outcome of this study. This timeframe was selected as it represents a standard CR program. Measurements post-Stage 2 (13 weeks), and at 6- and 12-month follow-up, will be secondary outcomes.
Peak VO2: The sample size calculation was for change in VO2peak(ml/kg/min) between the two groups. A clinically significant change was taken as 1 MET (3.5 ml/kg/min) based on the work of Kodama et al. (2009), which indicated this would reduce the risk of cardiovascular disease and all cause mortality by 15% and 13% respectively. It was assumed that the standard deviation of the change in VO2peak would be 4.75 ml/kg/min, based on the work of Moholdt et al. in 59 patients post CABG [Moholdt, 2009). Therefore with power of 0.9 and a 0.05 level of significance, 80 participants would be required. Accounting for a 20% loss to follow-up, a total of 100 participants will be recruited.

All statistical analyses will be carried out on an intention-to-treat (ITT) basis unless otherwise stated. Continuous variables will be described using mean (standard deviation) or median (interquartile range), while categorical variables will be described using frequencies (percentages). Though our design will randomly assign participants, we will assess any possible imbalances in baseline variables between HIIT and MICT groups that could potentially affect the impact of HIIT intervention on the outcomes. Pearson’s Chi-square test or Fisher’s exact test will be applied to assess categorical variables. Depending on normality, student’s t-test or the Mann–Whitney U-test will be applied to assess continuous variables. Continuous outcomes including the primary outcomes of VO2peak and VAT will be analysed using random effects multivariable linear regression, while categorical outcomes will be analysed using random effects multivariable logistic regression. Conditional on the degree of dispersion, either mixed effects poisson or negative binomial regression will be used to model count data. Irrespective of modelling approach, correlation of observations within participants and over follow-up will be accounted for by the inclusion of random intercepts and slopes into the regression modelling. All models will treat intervention as a fixed effect and adjust for all possible measured confounders. To test whether intervention effect was modified by the presence of model covariates, all models will be extended to include the presence of interaction terms. Sensitivity analyses will be conducted testing model functional forms, the variables to be used, and the impact of influential outliers on estimates. In addition, per-protocol analyses will also be conducted to assess the robustness of our findings for various degrees of non-adherence and protocol violation. Where appropriate and under the assumption of missing at random, multiple imputation will be used to account for missing data, with results being compared to those produced by complete case analyses. All analyses will be conducted using SPSS version 21. The level of statistical significance will be set at 0.05 and all hypothesis tests will be two-sided.

Recruitment
Recruitment status
Completed
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)
QLD
Recruitment hospital [1] 4696 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 12269 0
4066 - Auchenflower

Funding & Sponsors
Funding source category [1] 292428 0
University
Name [1] 292428 0
University of Queensland (School of Human Movement and Nutrition Sciences)
Address [1] 292428 0
School of Human Movement and Nutrition Sciences
Human Movement Studies Building (#26B)
The University of Queensland
St Lucia, QLD, 4072
Country [1] 292428 0
Australia
Funding source category [2] 293101 0
Charities/Societies/Foundations
Name [2] 293101 0
Wesley Medical Research
Address [2] 293101 0
East Wing, Level 8
The Wesley Hospital
Chasely St
Auchenflower, 4066
Country [2] 293101 0
Australia
Funding source category [3] 296288 0
Government body
Name [3] 296288 0
National Health and Medical Research Council
Address [3] 296288 0
Research Committee Secretariat NHMRC GPO Box 1421 Canberra ACT 2601
Country [3] 296288 0
Australia
Primary sponsor type
University
Name
University of Queensland (School of Human Movement and Nutrition Sciences)
Address
School of Human Movement and Nutrition Sciences
Human Movement Studies Building (#26B)
The University of Queensland
St Lucia, QLD, 4072
Country
Australia
Secondary sponsor category [1] 291117 0
Hospital
Name [1] 291117 0
The Wesley Hospital (Cardiac Rehabilitation)
Address [1] 291117 0
Cardiac Rehabilitation Department
East Wing, Level B1
The Wesley Hospital
Chasely St, Auchenflower, QLD, 4066
PO Box 499, Toowong, 4066
Country [1] 291117 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293888 0
UnitingCare Health Human Research Ethics Committee
Ethics committee address [1] 293888 0
UnitingCare Health Human Research Ethics Committee
The Wesley Hospital
PO Box 499
Auchenflower, Qld, 4066
Ethics committee country [1] 293888 0
Australia
Date submitted for ethics approval [1] 293888 0
24/08/2015
Approval date [1] 293888 0
24/11/2015
Ethics approval number [1] 293888 0
1522
Ethics committee name [2] 294604 0
University of Queensland Institutional Human Research Ethics
Ethics committee address [2] 294604 0
Human Ethics, Research Management Office
UQ Research and Innovation
Cumbrae-Stewart Building (#72)
St Lucia Campus
BRISBANE QLD 4072
Ethics committee country [2] 294604 0
Australia
Date submitted for ethics approval [2] 294604 0
07/12/2015
Approval date [2] 294604 0
09/12/2015
Ethics approval number [2] 294604 0
2015001938

Summary
Brief summary
This project aims to investigate if a high intensity interval training (HIIT) program offers greater improvements, than moderate intensity continuous exercise, for intra-abdominal fat, fitness, inflammation, cardiovascular risk factors, and exercise adherence. The project will also investigate whether HIIT can be successfully integrated into a hospital-based cardiac rehabilitation program as a practical and safe alternative to moderate intensity exercise. We expect high intensity interval training will be a safe and practical option. This will lead to the, development of a protocol to guide cardiac rehabilitation programs on how to incorporate HIIT as a standard exercise option for patients.
Trial website
www.fitrheartstudy.com
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61698 0
Mrs Jenna Taylor
Address 61698 0
Cardiac Rehabilitation Department
East Wing, Level B1
The Wesley Hospital
Chasley St, Auchenflower, QLD, 4066
PO Box 499, Toowong, QLD, 4066
Country 61698 0
Australia
Phone 61698 0
+61438526205
Fax 61698 0
Email 61698 0
j.kirchner@uq.net.au
Contact person for public queries
Name 61699 0
Mrs Jenna Taylor
Address 61699 0
Cardiac Rehabilitation Department
East Wing, Level B1
The Wesley Hospital
Chasley St, Auchenflower, QLD, 4066
PO Box 499, Toowong, QLD, 4066
Country 61699 0
Australia
Phone 61699 0
61499784790
Fax 61699 0
Email 61699 0
FITRheartstudy@gmail.com
Contact person for scientific queries
Name 61700 0
Mrs Jenna Taylor
Address 61700 0
Cardiac Rehabilitation Department
East Wing, Level B1
The Wesley Hospital
Chasley St, Auchenflower, QLD, 4066
PO Box 499, Toowong, QLD, 4066
Country 61700 0
Australia
Phone 61700 0
+61438526205
Fax 61700 0
Email 61700 0
j.kirchner@uq.net.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary