Please be advised that due to the high volume of submissions, the ANZCTR is currently experiencing delays in processing submissions from those outside of Australia and New Zealand. As the ANZCTR is funded by Australia and New Zealand, we must prioritise submissions from these countries first. International submissions should allow additional time for registration. Apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000846123
Ethics application status
Approved
Date submitted
29/05/2019
Date registered
14/06/2019
Date last updated
14/06/2019
Date data sharing statement initially provided
14/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of cardiorespiratory fitness and acute aerobic exercise on liver metastases blood flow
Scientific title
The effect of cardiorespiratory fitness and acute aerobic exercise on liver metastases blood flow in patients with stage IV cancer
Secondary ID [1] 298311 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver metastases 312942 0
Condition category
Condition code
Cancer 311432 311432 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will complete a standardised a single YMCA fitness test. The test is performed on a cycle ergometer and involves three submaximal stages of increasing intensity. The test involves the participant pedaling at a cadence of 50 revolutions per minute (rpm) for at least 3 minutes at each of the three stages. If the heart rate at the second and third minutes varies by more than 5 bpm, the stage is extended for one minute or until steady state is achieved. Heart rate and VO2 of the last minute of each stage will be plotted. This is then extrapolated to the age-predicted maximum heart rate to predict maximal oxygen
consumption (VO2max).

The participant will rest for at least 10 minutes prior to commencing the next bout of exercise. Heart rate, blood pressure and oxygen saturation will be monitored throughout the rest period. The rest period will be extended beyond 10 minutes if required, until physiological measures return to baseline levels.

Participants will complete a single bout of moderate intensity exercise. The participant will cycle at 46-56% VO2max (40-50% heart rate reserve (HRR)) for at least 5 minutes, until steady state heart rate has been reached.

As per the YMCA test, the participant will rest for at least 10 minutes following exercise, until
physiological markers return to baseline levels.

A sub-group of 18 participants will complete three short (5 min) bouts of exercise in a single session. One will be at a low intensity (27-37% VO2max/20-30% HRR), one at a moderate intensity (46-56% VO2max/40-50% HRR) and one at a high intensity (64-74% VO2max/60-70% HRR). Individuals will be invited to participate in the sub-study if they possess aerobic fitness (VO2peak) of 18 ml/kg/min or above, as estimated during the aerobic fitness testing. The order of intensities performed will be randomised using a computer-generated random numbers list. Sealed envelopes containing the randomised exercise sequence will be opened in front of the participant on the day of testing. Following each exercise condition, the participant will rest for at least 10 minutes, until physiological markers return to baseline levels.

All exercise interventions will be administered in a one-on-one mode, and will be supervised by an accredited Exercise Physiologist.
Intervention code [1] 314543 0
Other interventions
Comparator / control treatment
Participants act as their own control. Resting physiological and blood flow measures will be considered as the control treatment (no exercise).
Control group
Active

Outcomes
Primary outcome [1] 320184 0
Blood flow in liver tumour and blood flow in hepatic artery will be measured using Doppler ultrasound imaging.
Timepoint [1] 320184 0
Immediately post-exercise for 10 minutes
Secondary outcome [1] 370794 0
Heart rate response to exercise using a wearable heart rate monitor.
Timepoint [1] 370794 0
Immediately pre-exercise for 15 minutes, during YMCA test for 12 minutes, immediately post-YMCA for 10 minutes, during exercise for 5 minutes and immediately post-exercise for 10 minutes
Secondary outcome [2] 371124 0
Blood pressure response to exercise using a sphygmomanometer
Timepoint [2] 371124 0
Immediately pre-exercise for 15 minutes, during YMCA test for 12 minutes, immediately post-YMCA for 10 minutes, during exercise for 5 minutes and immediately post-exercise for 10 minutes
Secondary outcome [3] 371125 0
Oxygen saturation response to exercise using a pulse oximeter
Timepoint [3] 371125 0
Immediately pre-exercise for 15 minutes, during YMCA test for 12 minutes, immediately post-YMCA for 10 minutes, during exercise for 5 minutes and immediately post-exercise for 10 minutes
Secondary outcome [4] 371126 0
Cardiorespiratory fitness, specifically submaximal VO2, using a metabolic cart
Timepoint [4] 371126 0
During exercise

Eligibility
Key inclusion criteria
a. Voluntarily signed the informed consent form
b. Ability to speak and understand english
c. Aged over 18 years
d. Histologically confirmed stage IV cancer with a liver metastasis appropriate and easily accessible for Doppler ultrasound.
e. ECOG 0-2
f. Treating oncologist approval
g. Willingness and ability to comply with all study procedures
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Present with an acute systemic infection or fever
b. Presence of any condition that is a contraindication to exercise
c. Presence of orthopaedic problems, peripheral neuropathy or pain that would limit lower body exercise
d. Currently taking beta-blocker medications

Study design
Purpose of the study
Educational / counselling / training
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
Other
Other design features
A total of 80 participants will be enrolled and undergo aerobic fitness testing and a bout of moderate intensity exercise. A sub-group of 18 participants will also complete two additional bouts of exercise. To ensure capacity to complete the two additional exercise bouts, individuals will be invited to participate in the sub-study if they possess aerobic fitness (VO2peak) of 18 ml/kg/min or above, as estimated during the aerobic fitness testing. The order of intensities performed will be randomised using a computer-generated random numbers list. Sealed envelopes containing the randomised exercise sequence will be opened in front of the participant on the day of testing.
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
Descriptive statistics will be used to describe age, height, weight, physical activity, quality of life, fatigue, oxygen consumption, ultrasound data, recruitment rate, exercise compliance and adverse events. The relationship between blood flow and cardiorespiratory fitness will be evaluated using inferential statistics. One-way repeated ANOVA will be used to compare blood flow across the three intensities, within subjects. This will be followed by a- priori post hoc testing using T-tests to examine if there are significant difference between low to moderate and between moderate to high exercise intensities. Hypotheses will be tested using a significance level of 0.05 and a power of 95%.

Results will guide development of future phase II/III studies and will provide objective data on which to estimate magnitude of effects and sample sizes.

Recruitment
Recruitment status
Not yet 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)
NSW
Recruitment hospital [1] 13821 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 26579 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 302852 0
University
Name [1] 302852 0
University of Sydney
Address [1] 302852 0
Cumberland Campus 75 East Street, Lidcombe, NSW, 2141
Country [1] 302852 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Cumberland Campus 75 East Street, Lidcombe, NSW, 2141
Country
Australia
Secondary sponsor category [1] 302803 0
None
Name [1] 302803 0
Address [1] 302803 0
Country [1] 302803 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303427 0
Sydney Local Health District Ethics Review Committee Royal Prince Alfred Hospital Zone
Ethics committee address [1] 303427 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 303427 0
Australia
Date submitted for ethics approval [1] 303427 0
03/04/2019
Approval date [1] 303427 0
14/05/2019
Ethics approval number [1] 303427 0
X19-0123 & 2019/ETH00544

Summary
Brief summary
The main purpose of this study is to assess if there is an association between cardiorespiratory fitness and acute aerobic exercise on tumour blood flow in patients with cancer that has spread to the liver. A secondary aim of the study is to determine the most effective exercise intensity for increasing tumour blood flow.

Who is it for?
You may be eligible for this study if you are aged over 18 and diagnosed with stage IV cancer with a liver metastases.

Study details
All participants in this study will be required to attend a single visit. Participants will perform an aerobic fitness test (YMCA). After a rest period, participants will ride on an exercise bike for 5 minutes, or take part in the sub-study which participants will complete 3 cycling tasks of varying difficulty. Each will last for 5 minutes and there will be a rest period in between each one. Physiological measurements will be taken before, during and after the intervention, including blood pressure, heart rate and oxygen saturation, as well as oxygen consumption and ultrasound measures.

The study will extend the work of a current pilot study, investigating the safety and feasibility of intra-infusion aerobic exercise and help progress towards clinical application. The results will not provide a full picture into the mechanism or relationship of tumour blood flow and chemotherapy delivery but rather provide a platform for further research.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93642 0
Dr Kate Edwards
Address 93642 0
Rm K207, Cumberland Campus, The University of Sydney, Lidcombe, NSW, 2141
Country 93642 0
Australia
Phone 93642 0
+61 2 9036 7396
Fax 93642 0
Email 93642 0
kate.edwards@sydney.edu.au
Contact person for public queries
Name 93643 0
Dr Kate Edwards
Address 93643 0
Rm K207, Cumberland Campus, The University of Sydney, Lidcombe, NSW, 2141
Country 93643 0
Australia
Phone 93643 0
+61 2 9036 7396
Fax 93643 0
Email 93643 0
kate.edwards@sydney.edu.au
Contact person for scientific queries
Name 93644 0
Dr Kate Edwards
Address 93644 0
Rm K207, Cumberland Campus, The University of Sydney, Lidcombe, NSW, 2141
Country 93644 0
Australia
Phone 93644 0
+61 2 9036 7396
Fax 93644 0
Email 93644 0
kate.edwards@sydney.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
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
Summary results
No Results