Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000716268
Ethics application status
Approved
Date submitted
24/04/2018
Date registered
1/05/2018
Date last updated
1/09/2020
Date data sharing statement initially provided
1/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Prospective Athlete Heart Study- elucidating genetic determinants of cardiac remodelling using endurance exercise as an environmental stress.
Scientific title
The Prospective Athlete Heart Study- elucidating genetic determinants of cardiac remodelling using endurance exercise as an environmental stress.
Secondary ID [1] 294706 0
None
Universal Trial Number (UTN)
U1111_1212_8349
Trial acronym
Pro@Heart
Linked study record
ACTRN12618000711213

Health condition
Health condition(s) or problem(s) studied:
Cardiac Remodelling 307567 0
Athlete's Heart 307568 0
Heart Failure 307569 0
Genetics 307571 0
Cardiac arrythmia's 307572 0
Condition category
Condition code
Cardiovascular 306641 306641 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
A prospective comparison of endurance athletes and non-athletes which will assess the primary hypothesis that rare variants in 65 genes associated with abnormalities of cardiac structure will be more prevalent in those athletes with the greatest cardiac remodelling after 2 years of intense endurance exercise training.
All subjects will undergo detailed assessment of cardiac structure and exercise capacity at baseline, after two years, 5 years and every 5 years after that for 25years total.
Testing will include, anthropometry measures (height, weight, BP), echocardiogram, electrocardiogram, 24h holter monitoring, Cardiac Magnetic Resonance Imaging with exercise, VO2 max test, 12 month exercise diary, blood samples, Dexa scan.
Selection for genotyping after 2 years.
Intervention code [1] 300999 0
Diagnosis / Prognosis
Comparator / control treatment
Endurance exercise represents the ideal model for testing genetic–environmental interactions. Therefore endurance athletes will be compared to a non-athletic control group.
Control group
Active

Outcomes
Primary outcome [1] 305638 0
Assess the prevalence of rare variants in cardiac structural genes relative to Left Ventricular Mass index in endurance athletes and non-athletes by performing next generation sequencing in 65 cardiac genes extracting DNA from circulating white cells.
Timepoint [1] 305638 0
2 years after baseline testing
Primary outcome [2] 305641 0
left ventricular mass index (LVMi) on cardiac magnetic resonance imaging (CMR)
Timepoint [2] 305641 0
2 years after baseline testing
Secondary outcome [1] 346005 0
Assess the changes in cardiac structure (cardiac mass and geometry) by measurement of LV and RV volumes and myocardial mass using cardiac magnetic resonance (CMR) with gadolinium contrast
Timepoint [1] 346005 0
baseline, 2 years
Secondary outcome [2] 346007 0
Assess fitness status by VO2 max (measurement of maximum oxygen metabolism) test on bicycle ergometer with metabolic cart
Timepoint [2] 346007 0
baseline, two years, 5 years and every 5 years after that for 25 years.
Secondary outcome [3] 346137 0
Assess the prevalence of cardiac arrhythmia's on electrocardiogram and 24h holter monitoring
Timepoint [3] 346137 0
baseline, two years, 5 years and every 5 years after that for 25 years
Secondary outcome [4] 346139 0
Assessment of myocardial fibrosis using T1-weighted inversion recovery times on cardiac MRI
Timepoint [4] 346139 0
Baseline and 2 years
Secondary outcome [5] 346140 0
Measurement of torsion, strain and strain rate using transthoracic echocardiogram, including Doppler and 3D volumetric acquisitions.
Timepoint [5] 346140 0
baseline, 2 years
Secondary outcome [6] 346141 0
Blood samples to measure fasting lipid profile, cardiac biomarkers (Troponin I, Brain Natriuretic Peptide), Hs_CRP, FBE and U&E.
Timepoint [6] 346141 0
baseline, two years
Secondary outcome [7] 346142 0
Resting blood pressure and blood pressure response during exercise measured in office after lying supine for 10 minutes and during the VO2 max test
Timepoint [7] 346142 0
baseline, 2 years
Secondary outcome [8] 346144 0
Measurement of body composition and bone mineral density by a dual energy X-ray absorptiometry (DEXA) scan (whole body, spine and hip scan)
Timepoint [8] 346144 0
baseline, two years.
Secondary outcome [9] 346147 0
Quantify exercise duration and intensity during one week from self-report on an exercise diary or by recording on an electronic fitness device
Timepoint [9] 346147 0
baseline, two years

Eligibility
Key inclusion criteria
Endurance athletes, male and female, aged 16-23 years, competing in endurance sports in which aerobic fitness conditioning is a principal component of performance. Aiming to be involved in competition and high level training for more than 5 years.
Non-athletes, male and female, aged 16-23 years, less than 2 hours of endurance activity per week, not competing in an endurance sport, not enrolled in a fitness program to improve fitness.
Minimum age
16 Years
Maximum age
23 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known cardiovascular disease
- Cigarette smoking (current or previous)
- Moderate or severe hypertension.
- Use of performance enhancing drugs.
- A contraindication to magnetic resonance imaging

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Prospective exercise cohort (320 athletes; 220 males, 100 females)
Non-athletic controls (110 males, 50 females)
The reason for recruiting a cohort of approximately two-thirds male is a pragmatic balance between opportunities for recruitment, given greater male participation in endurance sport, balanced against the opportunity to provide female athletic data which is under-represented in the scientific literature.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
23/05/2016
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
31/12/2044
Actual
Sample size
Target
480
Accrual to date
140
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 10780 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment hospital [2] 10781 0
South Australian Health and Medical Research Institute (SAHMRI) - Adelaide
Recruitment postcode(s) [1] 22518 0
3004 - Melbourne
Recruitment postcode(s) [2] 22519 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 10351 0
Belgium
State/province [1] 10351 0
Antwerp, Brabant

Funding & Sponsors
Funding source category [1] 299311 0
Government body
Name [1] 299311 0
NHMRC APP1109322
Country [1] 299311 0
Australia
Funding source category [2] 299315 0
Charities/Societies/Foundations
Name [2] 299315 0
National Heart Foundation
Country [2] 299315 0
Australia
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
99 Commercial Road
Melbourne
VIC 3004
Country
Australia
Secondary sponsor category [1] 298580 0
None
Name [1] 298580 0
Address [1] 298580 0
Country [1] 298580 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300221 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 300221 0
55 Commercial Road
Melbourne
VIC 3004
Ethics committee country [1] 300221 0
Australia
Date submitted for ethics approval [1] 300221 0
23/07/2015
Approval date [1] 300221 0
21/10/2015
Ethics approval number [1] 300221 0
333/15

Summary
Brief summary
The heart can be stimulated to change its size and shape. The heart changing size and shape is a normal adaptation; however, in certain cases this adaptation can become harmful.
Change in heart structure predicts heart events (eg. congestive heart failure, abnormal heart beats). Heart size and shape varies considerably between people; it is currently unknown what accounts for most of this variability. Previous studies suggest a genetic contribution; however, no studies have yet identified the specific changes in a person’s genetic makeup which explain why one person has a bigger heart than another.
This study aims to identify rare variants in specific genes that are related to abnormal changes in heart structure. This study will do so by tracking changes in heart structure related to endurance exercise training as well as normal aging. Endurance athletes with the greatest change in heart structure will have select genes compared to endurance athletes with the least change in heart structure after 2 years of training. Additionally these gene profiles will be compared to non-endurance athletes who have the greatest and least change in heart structure over a 2-year period. In this way investigators can identify which gene variants are related to highly adaptive versus less adaptive hearts.
Identifying gene variants related to heart size may help identify individuals at risk of abnormalities in which the heart enlarges too much. Identifying at-risk individuals allows doctors to identify people who may benefit from advice or treatments that may prevent problems from developing.
Trial website
https://www.baker.edu.au/research/clinical-trials/pro-heart-trial
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82962 0
A/Prof Andre La Gerche
Address 82962 0
Baker Heart and Diabetes Institute
Alfred Centre, level 4
99 commercial Road
Melbourne
VIC 3004
Country 82962 0
Australia
Phone 82962 0
+61 3 8532 1169
Fax 82962 0
Email 82962 0
[email protected]
Contact person for public queries
Name 82963 0
Ms Kristel Janssens
Address 82963 0
Baker Heart and Diabetes Institute
Alfred Centre, level 4
99 commercial Road
Melbourne
VIC 3004
Country 82963 0
Australia
Phone 82963 0
+61 3 8532 1169
Fax 82963 0
Email 82963 0
[email protected]
Contact person for scientific queries
Name 82964 0
A/Prof Andre La Gerche
Address 82964 0
Baker Heart and Diabetes Institute
Alfred Centre, level 4
99 commercial Road
Melbourne
VIC 3004
Country 82964 0
Australia
Phone 82964 0
+61 3 8532 1169
Fax 82964 0
Email 82964 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
EmbaseRationale and design of the PROspective ATHletic Heart (Pro@Heart) study: Long-term assessment of the determinants of cardiac remodelling and its clinical consequences in endurance athletes.2022https://dx.doi.org/10.1136/bmjsem-2022-001309
N.B. These documents automatically identified may not have been verified by the study sponsor.