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Trial registered on ANZCTR


Registration number
ACTRN12618001155280
Ethics application status
Approved
Date submitted
27/06/2018
Date registered
13/07/2018
Date last updated
24/01/2019
Date data sharing statement initially provided
24/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
EX-HEART TRIAL: Exercise for heart health in prostate cancer
Scientific title
EX-HEART TRIAL: Evaluating the impact of exercise on cardiac remodeling in men with prostate cancer undergoing androgen deprivation therapy
Secondary ID [1] 294974 0
Nil
Universal Trial Number (UTN)
Trial acronym
EX-HEART TRIAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 307974 0
Cardiovascular disease 307975 0
Condition category
Condition code
Cardiovascular 307013 307013 0 0
Normal development and function of the cardiovascular system
Cancer 307511 307511 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The 3-month periodised exercise intervention will involve three supervised exercise sessions per week. The exercise sessions will take approximately 30-60 minutes and will be supervised by an experienced exercise physiologist. Each participant will be asked to complete additional unsupervised exercise training (walking) for at least ~60 minutes per week to equate to the American College of Sports Medicine exercise and cancer roundtable recommendations of 150 minutes of aerobic exercise per week. The aerobic exercise training program will comprise of moderate intensity continuous training, moderately vigorous intensity interval training, and high intensity interval training each week and will follow an individualized training prescription based on participants’ baseline cardiopulmonary exercise test (CPET). The aerobic exercise training program will follow a athletic mesocycle approach; moderate continuous exercise training for month one and a combination of moderate intensity continuous training, moderately vigorous intensity interval training, and high intensity interval training for month two and three. Exercise intensity will be progressed each week by 7%-10%, depending on the baseline exercise capacity and training history of the participant. All participants will complete the aerobic exercise training on a cycle ergometer and/or treadmill. The resistance training program will be completed twice per week for 3 months. The progressive resistance training program will involve 5-6 exercises that target the major upper and lower body muscle groups. The initial intensity will be set to 60% of 1-RM (i.e. 60% of the maximal weight that can be lifted one time) at 3 sets of 12 repetitions. Exercise prescription will be progressive and modified according to individual response with the aim to increase the load and volume by 10% each week, in accordance with the American College of Sports Medicine guidelines for cancer survivors. Compliance and attendance (including the reason for any missed sessions) will be tracked throughout the program by the exercise physiologist.
Intervention code [1] 301296 0
Lifestyle
Intervention code [2] 301297 0
Rehabilitation
Intervention code [3] 301298 0
Treatment: Other
Comparator / control treatment
The usual care group will have no formalised exercise intervention during the research study. During the research study period, participants will be advised to stay physically active and continue to exercise at same level as entering the study. To minimise drop-out and drop-in, the usual care arm will be offered the supervised intervention after the follow- up period (12- months).

A healthy control group will be recruited for this study for comparison to men with prostrate cancer receiving ADT. The healthy control group will receive no formalised exercise intervention during the research study. During the research study period, participants will be advised to stay physically active and continue to exercise at same level as entering the study.
Control group
Active

Outcomes
Primary outcome [1] 306046 0
Change in left ventricular mass to volume ratio will be assessed with cardiac magnetic resonance imaging (CMR). Proportion of participants with a > 10% change in left ventricular mass to volume ratio will be assessed with CMR and Right Vol analysis software. Cardiac volumes (end-diastolic and end-systolic volume) will be calculated using the contouring technique in end-diastole and end-systole of each cardiac cycle.
Timepoint [1] 306046 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy (primary endpoint)
Secondary outcome [1] 347420 0
Echocardiographic indices of systolic (left ventricular ejection fraction, global longitudinal strain) and diastolic function (filling velocities, relaxation times) will be assessed by a trained trans-thoracic sonographer.


Timepoint [1] 347420 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [2] 347422 0
Maximal oxygen uptake (absolute and relative) will be assessed with a cardiopulmonary exercise test on an upright cycle ergometer with breath by breath expired gas analysis.
Timepoint [2] 347422 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [3] 347423 0
Cardiovascular disease risk will b assessed using the Framingham risk score to estimate 10-year cardiovascular risk.
Timepoint [3] 347423 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [4] 347424 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based serum lipid markers (total cholesterol)
Timepoint [4] 347424 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [5] 347425 0
Flow-mediated dilation will be acquired using vascular ultrasound imaging of baseline and peak diameter and velocity of the brachial artery prior to and following artery occlusion.
Timepoint [5] 347425 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [6] 347426 0
Carotid to femoral pulse wave velocity will be measured by collecting arterial pressure at both carotid and femoral sites. Each recording length will be acquired for ~10 seconds (equating to approximately 10 cardiac cycles). Pulse wave velocity will be recorded in millimetres per second.

Pulse wave analysis will be evaluated using on-invasive tonometry to measure the central pressure wave form of the ascending aorta via the radial artery. Augmentation index will be estimated by calculating the ratio of augmentation to the central pulse pressure waveform (expressed as a percentage).
Timepoint [6] 347426 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [7] 347427 0
Body composition - regional and whole body lean mass will be assessed by Dual-Energy X-ray Absorptiometry (DXA)
Timepoint [7] 347427 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [8] 347428 0
Timed stair climb power test will be used to assess lower limb muscular power. Participants will be instructed to climb a flight of stairs (12 stairs per flight, 17-cm step) without the use of the handrail.
Timepoint [8] 347428 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [9] 347429 0
Health-related quality of life will be assessed using the EORTC QLQ-30 and prostate cancer specific module EORTC-QLQ-PR25.
Timepoint [9] 347429 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [10] 347430 0
Cancer related fatigue will be assessed using the Functional Assessment of Chronic Illness Therapy (FACT-IT Fatigue).
Timepoint [10] 347430 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [11] 347431 0
Sleep quality will be assessed using the Pittsburgh Sleep Quality Index
Timepoint [11] 347431 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [12] 347432 0
Exercise levels will be assessed using modified Godin Leisure Time Exercise Questionnaire
Timepoint [12] 347432 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [13] 348313 0
Aortic pulse-wave velocity and change in aortic diameter from systole to diastole will be used as indices of aortic stiffness. These will be obtained from images of the proximal ascending and descending aorta taken during the CMR.
Timepoint [13] 348313 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [14] 349018 0
Cancer-specific psychological distress will be assessed using the brief symptom inventory (BSI 18)
Timepoint [14] 349018 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [15] 349019 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based cardiac biomarkers (Troponin I)
Timepoint [15] 349019 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [16] 349020 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based inflammatory markers (C-reactive protein and Interleukin-6)
Timepoint [16] 349020 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [17] 349274 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based serum lipid markers (triglycerides)
Timepoint [17] 349274 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [18] 349275 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based serum lipid markers (high-density lipoprotein)
Timepoint [18] 349275 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [19] 349276 0
A 15 mL fasted blood sample will be taken for the assessment of blood-based serum lipid markers (low-density lipoprotein)
Timepoint [19] 349276 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [20] 349277 0
Bone mineral density of hip and lumbar spine will be assessed by Dual-Energy X-ray Absorptiometry (DXA)
Timepoint [20] 349277 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy
Secondary outcome [21] 349371 0
Body composition - fat mass will be assessed by Dual-Energy X-ray Absorptiometry (DXA)
Timepoint [21] 349371 0
(1) Baseline - currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)
(2) 3-month follow up - 3-months since first administration of androgen deprivation therapy.
(3) 12-months - 12-months since first administration of androgen deprivation therapy

Eligibility
Key inclusion criteria
The inclusion criteria for the prostate cancer group are:
• Histologically confirmed prostate cancer
• 40 years and older
• Currently receiving or scheduled to receive androgen deprivation therapy (<1 month of initiating therapy)

Additionally, 10 aged-matched control participants will be recruited to assess the trajectory of change in cardiovascular function. Men will be included if they are male and have not been diagnosed with cancer.
Minimum age
40 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
The exclusion criteria for the prostate cancer group and age-matched control are:
• Unstable heart condition determined by study doctor and/or general practitioner
• Previously received ADT or chemotherapy for the treatment of a previous cancer
• Acute illness or any musculoskeletal, cardiovascular or neurological disorder that
could inhibit exercise or put participants at risk during exercise testing
• A contraindication to cardiac magnetic resonance imaging is a metallic implant or cardiac pacemaker


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)
Allocation concealment will be completed by an independent researcher external to the research project using a computer generated random number generator to randomly allocate prostate cancer participants to exercise and control.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Following baseline assessments, prostate cancer participants will be randomly assigned using a 1:1 group allocation method by central randomization by computer. Written informed consent will be required prior to any testing or randomization. Participants who dropout prior to completing baseline testing will not be randomised. Participants will be stratified by age (>=68 years or <68 years) and cardiovascular disease risk (low vs high). The aged-matched control group will not be randomised but allocated to the prostate cancer usual care group using a 3:1 group allocation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
No previous research has examined the impact of exercise training on cardiac remodeling in men with prostate cancer receiving ADT, therefore this study will be an exploratory study. Sample size calculations were based previous research examining the influence of exercise training and usual care on cardiac remodeling, which demonstrated a moderate-large standardised effect (d = 0.50-0.82) following exercise training. Therefore, to detect a clinically meaningful effect in LV mass to volume ratio (between–groups), a sample size of 25 participants per group is required to detect a large standardised effect (d =0.82) at 80% power and a 0.05 and within-participant difference, sample size of 16 is required to detect moderate to large standardised effect (d =0.76), assuming there would be minimal change in the usual care group. To obtain complete data and accounting for participant drop outs, we will increase our sample size to 31 participants per group (attrition rate of 25%). Previous experience in exercise and cancer interventional trials indicates an attrition rate of ~20% during a 3-12 month is appropriate for an intervention trial. The aged-matched controls will be recruited from a convenience sample at a 3:1 (prostate cancer: aged-matched healthy controls) ratio. Therefore, we will require a total of 31 prostate cancer participants per group to be adequately powered to address these hypotheses in men receiving ADT.

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)
VIC
Recruitment hospital [1] 11025 0
The Alfred - Prahran
Recruitment postcode(s) [1] 22818 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 299564 0
University
Name [1] 299564 0
Australian Catholic University
Address [1] 299564 0
Mary MacKillop Institute for Health Research, Australian Catholic University
Level 5, 215 Spring Street, Melbourne, VIC 3000
Country [1] 299564 0
Australia
Primary sponsor type
University
Name
Australian Catholic University
Address
Mary MacKillop Institute for Health Research, Australian Catholic University
Level 5, 215 Spring Street, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 298871 0
Other
Name [1] 298871 0
Baker Heart and Diabetes Institute
Address [1] 298871 0
Alfred Centre, Level 4 99 Commercial Road, Prahran, VIC 3004
Country [1] 298871 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300461 0
Alfred Health Ethics Committee
Ethics committee address [1] 300461 0
45 Commercial Road, Prahran, VIC 3004
Ethics committee country [1] 300461 0
Australia
Date submitted for ethics approval [1] 300461 0
11/12/2017
Approval date [1] 300461 0
09/03/2018
Ethics approval number [1] 300461 0
HREC/18/Alfred/4

Summary
Brief summary
The objective of this study is to a) determine the effects of androgen deprivation therapy (ADT) on the structure and function of the heart in prostate cancer patients and b) evaluate whether a targeted exercise intervention can reduce the ADT-induced impacts on the heart.

Who is it for?
You may be eligible to take part in the study if you are male aged 40 years and over, are diagnosed with prostate cancer and are currently receiving or scheduled to receive ADT (<1 month of initiating ADT). You may also be able to take part if you are male and have not been diagnosed with cancer.

Trial details:
Participants in this study will be randomly (by chance) divided into two groups. Participants in one group (i.e. exercise intervention group) will attend a 3 month physical exercise intervention program that involves aerobic (e.g. cycling) and resistance exercise (i.e. lifting weights) undertaken 3 times per week at various community based fitness centres/gyms throughout Melbourne. Exercise sessions will take approximately 60 minutes and will be conducted under the supervision of an accredited exercise physiologist. Participants in the second group (i.e. Usual care) will maintain usual care for 12 months and will then be offered the exercise intervention. All participants will be required to complete a number of tests at baseline, 3 months and 12 months in order to assess the function and structure of their heart, their physical fitness, and body composition. Participants will also be required to complete a number of questionnaires to assess their physical and psychological wellbeing.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 83734 0
A/Prof Prue Cormie
Address 83734 0
Mary MacKillop Institute for Health Research, Australian Catholic University
Level 5, 215 Spring Street Melbourne, VIC 3000
Country 83734 0
Australia
Phone 83734 0
+613 9230 8242
Fax 83734 0
Email 83734 0
prue.cormie@acu.edu.au
Contact person for public queries
Name 83735 0
Miss Ashley Bigaran
Address 83735 0
Mary MacKillop Institute for Health Research, Australian Catholic University
Level 5, 215 Spring Street Melbourne, VIC 3000
Country 83735 0
Australia
Phone 83735 0
+613 9230 8268
Fax 83735 0
Email 83735 0
ashley.bigaran@myacu.edu.au
Contact person for scientific queries
Name 83736 0
A/Prof Prue Cormie
Address 83736 0
Mary MacKillop Institute for Health Research, Australian Catholic University
Level 5, 215 Spring Street Melbourne, VIC 3000
Country 83736 0
Australia
Phone 83736 0
+613 9230 8242
Fax 83736 0
Email 83736 0
prue.cormie@acu.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The study protocol approved through the human research ethics committee does not permit secondary analysis
What supporting documents are/will be available?
No other documents available
Summary results
No Results