ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619000143123

Ethics application status

Approved

Date submitted

24/01/2019

Date registered

30/01/2019

Date last updated

28/09/2022

Date data sharing statement initially provided

30/01/2019

Date results information initially provided

28/09/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

Effects of exercise on Sexual function and CArdiovascular health in men with prostate cancer (ESCA) Study

Scientific title

Effects of exercise on Sexual function and CArdiovascular health in men with prostate cancer (ESCA) Study

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1225-6675

Trial acronym

ESCA

Linked study record

Health condition

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

Prostate Cancer

Sexual Function

Cardiovascular Disease Risk

Condition category

Condition code

Cancer

Prostate

Reproductive Health and Childbirth

Other reproductive health and childbirth disorders

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study involves two components. The first, an interventional study which will compare the effects of a 12-week exercise intervention to usual care in men who have, or who have previously had, prostate cancer. The second, a situational appraisal of this exercise intervention.

1. Exercise Intervention
The intervention will be a structured and individualised 12-week exercise program with the following components:
1) Participants will aim to complete 36 one-hour exercise sessions during this 12-week period (equating to three exercise sessions per week) in either a supervised gymnasium or in the participant’s community/home (if deemed the participant is able to safely and effectively complete their exercises unsupervised). If participants are unable to reach the target 36 sessions during these 12 weeks (i.e. they miss sessions due to excess treatment-related side effects), then they will be provided with the option of performing make-up sessions during this 12-week period (i.e. a participant may complete two sessions one week, then four sessions the following week). Alternatively, participants will be provided with the option of completing as many of the remaining sessions as possible during one additional week, making the intervention 13 weeks in duration (at most) for these participants.
2) Supervised exercise sessions will either be individual or group-based and be supervised by an accredited exercise physiologist (AEP). Unsupervised home-based exercise sessions will be individual.
3) The exercise intervention will taper from fully supervised (weeks 1-4) to partially supervised with self-managed sessions (weeks 5-12).
4) Each session will include a tailored exercise program, including a combination of high intensity aerobic and resistance exercises. These tailored exercise programs will be reviewed after each exercise session and will take into account each participant’s disease-status, exercise performance and exercise preferences. High-intensity exercise will be individualised to the participants’ cardiorespiratory fitness and closely monitored by the AEP.
5) Exercise programs will be delivered via a computer/phone application (Physitrack®) and thus can be accessed by participants both during their supervised and self-managed home-based sessions. Participants will be provided with coaching on how to use the phone application during their initial supervised exercise sessions. If participants are unwilling and/or unable to use the phone application, then a paper version of their exercise program will be provided, with the AEP then manually entering the participants completed exercises into Physitrack®.

2. Situational Appraisal
Princess Alexandra Hospital clinicians (medical oncologists, prostate cancer nurses, physiotherapists, and service managers) and intervention participants will be invited to attend focus groups. Participants will be required to attend one of two focus groups, lasting no longer than 90 minutes in duration. Participants will be asked questions regarding resource utilisation, the knowledge and skills needed to implement the intervention, as well as cultural and structure barriers and facilitators.

Intervention code [1]

Treatment: Other

Intervention code [2]

Prevention

Intervention code [3]

Lifestyle

Comparator / control treatment

Men who have, or who have previously had, prostate cancer who are randomised to the control group will continue with usual care (i.e. continue with their usual course of hormone therapy, chemotherapy, etc.; or continue with their normal health care, if not actively undergoing treatment for prostate cancer). Control group participants will be informed that they are not prohibited from exercising during the study period.

Control group

Active

Outcomes

Primary outcome [1]

Changes in erectile function and intercourse satisfaction (composite outcome), as assessed via the Abridged version of the International Index of Erectile Function (IIEF-5) questionnaire

Timepoint [1]

Baseline and 12 weeks (primary timepoint) after randomisation

Secondary outcome [1]

Changes in erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction (composite outcome), as assessed via the International Index of Erectile Function (IIEF) questionnaire

Timepoint [1]

Baseline and 12 weeks after randomisation

Secondary outcome [2]

Changes in macro vascular function, as assessed via Brachial-Artery Flow-mediated Dilation (BA-FMD) using doppler ultrasound

Timepoint [2]

Baseline and 12 weeks after randomisation

Secondary outcome [3]

Changes in Brain Blood Flow and Carotid Dilation, as assessed via carotid-artery flow-mediated dilation and neurovascular coupling using a doppler ultrasound and a Finapres NOVA System

Timepoint [3]

Baseline and 12 weeks after randomisation

Secondary outcome [4]

Changes in macro vascular structure, as assessed via Carotid Intima-media Thickness (CIMT) using doppler ultrasound

Timepoint [4]

Baseline and 12 weeks after randomisation

Secondary outcome [5]

Changes in macro vascular function, as assessed via Carotid Distensibility (CD) using a doppler ultrasound, a hand-held PowerLab tonometer connected to LabChart, and a Finapres NOVA System

Timepoint [5]

Baseline and 12 weeks after randomisation

Secondary outcome [6]

Changes in central blood pressures and pulse wave characteristics, as assessed via Pulse Wave Analysis (PWA) using a SphygmoCor XCEL PWA and PWV system

Timepoint [6]

Baseline and 12 weeks after randomisation

Secondary outcome [7]

Changes in central pulse transfer times, as assessed via Pulse Wave Velocity (PWV) using a SphygmoCor XCEL PWA and PWV system

Timepoint [7]

Baseline and 12 weeks after randomisation

Secondary outcome [8]

Changes in autonomic nervous system function, as assessed via Heart Rate Variability (HRV) using a resting 3-lead electrocardiogram

Timepoint [8]

Baseline and 12 weeks after randomisation

Secondary outcome [9]

Changes in autonomic nervous system function, as assessed via heart rate and blood pressure responses to both deep breathing and a Valsalva Manoeuvre using a Finapres NOVA System

Timepoint [9]

Baseline and 12 weeks after randomisation

Secondary outcome [10]

Changes in inflammatory blood markers, as assessed via levels of:
- Cardiac Troponin-I
- pro-Brain Natriuretic Peptide (pro-BNP)
- High-sensitivity C-reactive Protein (hs-CRP)
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [10]

Baseline and 12 weeks after randomisation

Secondary outcome [11]

Changes in oxidative stress as assessed via plasma nitrate and nitrite levels.
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [11]

Baseline and 12 weeks after randomisation

Secondary outcome [12]

Changes in metabolic and hormonal blood markers as assessed via;
- Low-density lipoprotein (LDL)
- High-density lipoprotein (HDL)
- Total cholesterol (TC)
- Triglycerides (TG)
- Fasting glucose
- Haemoglobin A1c (HbA1c)
- Insulin
- Insulin-like growth factor 1 (IGF-1)
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [12]

Baseline and 12 weeks after randomisation

Secondary outcome [13]

Changes in cytokine blood markers as assessed via;
- Interleukin 1 beta (IL-1beta)
- Interleukin 6 (IL-6)
- Interleukin 2 (IL-2)
- Tumor Necrosis Factor alpha (TNFalpha)
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [13]

Baseline and 12 weeks after randomisation

Secondary outcome [14]

Changes in prostate cancer cell growth, as assessed via cell culture analyses (using cell number assays and cell death assays).
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [14]

Baseline and 12 weeks after randomisation

Secondary outcome [15]

Changes in a hormonal blood marker, as assessed via levels of testosterone.
All bloods for Secondary Outcomes numbered 10-15 collected via 10mL and 6mL serum tubes, a 10mL Ethylenediaminetetraacetic acid (EDTA) tube, a 4mL Lith/Hep tube, and a 2mL glucose tube (32mL in total)

Timepoint [15]

Baseline and 12 weeks after randomisation

Secondary outcome [16]

Changes in state and trait anxiety, as assessed via the Hospital Anxiety and Depression Scale (HADS) questionnaire

Timepoint [16]

Baseline and 12 weeks after randomisation

Secondary outcome [17]

Changes in fatigue, as assessed via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale questionnaire

Timepoint [17]

Baseline and 12 weeks after randomisation

Secondary outcome [18]

Changes in participant's perceived performance status, as assessed via the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale

Timepoint [18]

Baseline and 12 weeks after randomisation

Secondary outcome [19]

Changes in cardiorespiratory fitness (VO2Peak), as assessed via a Cardiopulmonary Exercise Test (CPET) using a cycle ergometer and metabolic system

Timepoint [19]

Baseline and 12 weeks after randomisation

Secondary outcome [20]

Changes in body composition, as assessed via whole-body bone, muscle and fat mass using Dual Energy X-ray Absorptiometry (DEXA)

Timepoint [20]

Baseline and 12 weeks after randomisation

Secondary outcome [21]

Changes in body composition, as assessed via muscle cross sectional area and bone density of the tibia and femur using peripheral Quantitative Computed Tomography (pQCT)

Timepoint [21]

Baseline and 12 weeks after randomisation

Secondary outcome [22]

Changes in habitual physical activity and sedentary behaviours, as assessed via accelerometery using a ActiGraph GT3X+ accelerometer

Timepoint [22]

Baseline and 12 weeks after randomisation

Secondary outcome [23]

Adverse Events (AE) occurrence during the intervention period, as assessed via weekly face-to-face contact (at exercise sessions) from baseline to week 12. AE which might be directly related to the intervention (to be determined by an accredited exercise physiologist) will be assessed using the US Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE). Possible AE include:
- Cardiac events (e.g. Myocardial Infarction, Stroke, Cardiac Arrhythmia)
- Musculoskeletal events (e.g. Development of Lower Back Pain, Knee Pain)
- Treatment-related events (e.g. Fatigue development, Immunocompromised i.e. flu)
- Concurrent prostate cancer treatment-related events (e.g. Pain, Skin irritation)

Timepoint [23]

Every supervised exercise session from baseline to week 12, throughout the 12-week exercise intervention period

Secondary outcome [24]

Resource utilisation in both groups during the intervention period, as assessed via discussion in the situational appraisal component of the study. Discussion of labour (e.g. to deliver the intervention) and non-labour (e.g. gymnasium use, pain medication) costs. Resource use will be costed at market rates (e.g. industrial award rates for labour costs), for use in cost-effectiveness analyses.

Timepoint [24]

Following exercise intervention completion

Secondary outcome [25]

Evaluation of factors relating to participant adherence to the exercise intervention, as assessed via a Cancer Exercise Adherence Survey specially designed for this study

Timepoint [25]

Baseline (Intervention group ONLY)

Secondary outcome [26]

Changes in habitual dietary intake, as assessed via a three-day diet diary

Timepoint [26]

Baseline and 12 weeks after randomisation

Secondary outcome [27]

Changes in body composition, as assessed via:
- Weight
- Height
- Body mass index (BMI)
- Waist and hip circumferences
- Waist-to-hip ratio (WHR)

Timepoint [27]

Baseline and 12 weeks after randomisation

Eligibility

Key inclusion criteria

- Men with a histologically-confirmed diagnosis of prostate cancer
- Sexual dysfunction score of moderate (score = 8-11/25), mild-to-moderate (score = 12-16/25), or mild (score = 17-21/25), as assessed by the abridged version of the International Index of Erectile Function (IIEF-5)
- Undergoing watchful waiting, active surveillance, or previous or concurrent treatment with any anti-cancer treatment/s
- Aged >18 years
- >4 weeks since major surgery
- No co-morbid condition or falls risk that could prevent safe completion of the intervention
- Cognitively capable of consent

Minimum age

18 Years

Maximum age

No limit

Sex

Males

Can healthy volunteers participate?

Key exclusion criteria

- Planning to undergo surgery during the intervention period
- Any intellectual or physical disability which would make exercise intervention participation unsafe for the individual

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 is concealed at baseline. The randomisation process for this trial is performed by a person external to the study (an academic from The University of Queensland, St Lucia). A Chief Investigator for the trial then contacts the external person, who informs them of the participant’s randomisation at the conclusion of baseline testing sessions.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Individuals who consent to participate in the trial are randomised at a 1:1 ratio to either the intervention or control group by the external person. Randomisation is performed electronically online using permuted block randomisation.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

40 participants are required for >80% power to detect a clinically important mean difference of 6.1 points between groups at any assessment on the primary outcome (IIEF-5). This assumes up to 30% attrition, SD=5.5 and alpha=0.05.

Statistical analyses of raw data will be conducted on IBM SPPS Statistics for iOS. Categorical outcomes will be described using frequencies and proportions, and analysed using general estimating equations with a logistic regression model to account for repeated measures. ORs and 95% CIs will be reported. Control and intervention groups will be compared for continuous outcomes using mean/SD or median/interquartile range if not normally distributed. To account for the repeated measures, continuous outcome measures will be modelled using linear mixed-models. Assumptions of models will be examined by plotting the residuals using histograms and skewness and kurtosis measures. If the data do not meet assumptions, the 95% CIs will be bootstrapped to provide reliable estimates. Models will only be adjusted for characteristics that were unbalanced between groups and related to the outcome variable.

Recruitment

Recruitment status

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities
Participant recruitment difficulties

Date of first participant enrolment

Anticipated

4/02/2019

Actual

14/03/2019

Date of last participant enrolment

Anticipated

22/09/2023

Actual

22/01/2020

Date of last data collection

Anticipated

22/12/2023

Actual

25/05/2020

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Princess Alexandra Hospital - Woolloongabba

Recruitment postcode(s) [1]

4102 - Woolloongabba

Funding & Sponsors

Funding source category [1]

University

Name [1]

The University of Queensland

Address [1]

School of Human Movement and Nutrition Sciences, The University of Queensland, St Lucia, QLD, 4072

Country [1]

Australia

Primary sponsor type

University

Name

The University of Queensland

Address

School of Human Movement and Nutrition Sciences, The University of Queensland, St Lucia, QLD, 4072

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Metro South Human Research Ethics Committee

Ethics committee address [1]

PAH Centres for Health Research, Level 7, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland, 4102

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/11/2018

Approval date [1]

11/01/2019

Ethics approval number [1]

HREC/2018/QMS/47119

Summary

Brief summary

The purpose of this research study is to implement and evaluate a sexual function and cardiovascular health-targeted intervention during and following treatment for prostate cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or more and you have been, or have previously been, diagnosed with prostate cancer.

Study details
Participants in this study will be randomly allocated (by chance) to either 12-weeks of an exercise intervention or usual care. Participants in the exercise intervention group complete cardiorespiratory/aerobic, resistance and stretching exercises on 3 days of the week; which are individually tailored to each intervention participant. Participants in both groups are required to undertake assessments both before and after the 12-week intervention period. These assessments are related to sexual function, cardiovascular disease risk development and other health measures (e.g. body composition, blood markers, cardiorespiratory fitness).

Some participants will also be invited to attend a focus group discussion on the quality and feasibility of the intervention after intervention completion.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Tina Skinner

Address

Senior Lecturer in Exercise Physiology
School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072

Country

Australia

Phone

+61 7 3346 8810

Fax

[email protected]

Contact person for public queries

Name

Miss Natalie Vear

Address

PhD Candidate
School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072

Country

Australia

Phone

+61 4 7355 0978

Fax

[email protected]

Contact person for scientific queries

Name

Dr Tina Skinner

Address

Senior Lecturer in Exercise Physiology
School of Human Movement and Nutrition Sciences (#26B), Cnr Blair Drive & Union Road, The University of Queensland, St Lucia Campus, Queensland, 4072

Country

Australia

Phone

+61 7 3346 8810

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

As this is not a funded project and is part of a PhD student's work, we anticipate that the individual participants' data will not be made available on a publicly available repository. Should funding become available, or a journal request that the data be made available, we will apply for an amendment to make individual participant data available.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
876	Ethical approval				Ethical approval letter from Metro South Human Res... [More Details]	376595-(Uploaded-24-01-2019-11-12-42)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Conference abstract	No		Chung, E., Vear, N., Rhee, H., Skinner, T., Coombe... [More Details]
Conference abstract	No		Vear, N., Chung, E., Rhee, H., Coombes, J., Bailey... [More Details]

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically