Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000913774
Ethics application status
Approved
Date submitted
22/06/2022
Date registered
27/06/2022
Date last updated
26/05/2024
Date data sharing statement initially provided
27/06/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigating the effect of exercise on brain health in breast cancer patients
Scientific title
The Effect of Exercise on Cerebrovascular Function and Cognition in Breast Cancer Patients
Secondary ID [1] 307410 0
None
Universal Trial Number (UTN)
U1111-1279-6778
Trial acronym
CaFog Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive impairment 326740 0
Breast Cancer 326741 0
Condition category
Condition code
Neurological 323972 323972 0 0
Other neurological disorders
Cancer 323973 323973 0 0
Breast
Physical Medicine / Rehabilitation 323974 323974 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this study is to conduct a pilot study that investigates the effects of a supervised 8-week multimodal exercise intervention on cerebrovascular and cognitive function in female breast cancer patients.
This will be determined objectively by assessing the following outcomes:
(1) Cerebrovascular function, determined by measuring the cerebrovascular responsiveness (CVR) to both physiological (hypercapnia; 5% carbon dioxide) and psychological stimuli (cognitive battery)
(2) Cognitive function, determined by a battery of individual cognitive tasks that are summated to reflect total cognitive capacity.
Study design and ethical considerations
An 8-week quasi-randomised, controlled-trial of female breast cancer patients (n=24) who will be assigned to either a multimodal exercise intervention or waitlist group (control) will be conducted collaboratively at the University of Southern Queensland (USQ) Toowoomba, The Fit Lab Toowoomba, and Queensland X-ray Toowoomba.
Participants will visit USQ, The Fit Lab and Queensland X-ray prior to the commencement of the study, to establish baseline measurements. Participants will undergo anthropometric (body weight, height, hip, and waist circumference), functional capacity (60s sit-to-stand, 400m walk) and strength testing measurements under the supervision of an Accredited Exercise Physiologist at The Fit Lab. Dual-energy X-ray absorptiometry will be used to determine body composition measurements (lean and fat mass, bone mineral content and density) of the participants at Queensland X-Ray by an accredited technician. Participants will undergo cerebrovascular, cognitive, and cardiovascular measurements at USQ. Cognition will be measured via an iPad using the Trail Making Task Parts A and B, Spatial Span Test and the National Institute of Health (NIH) Toolbox. . Cerebrovascular measurements will be measured non-invasively using transcranial Doppler ultrasonography (TCD). These measurements include CVR to physiological (hypercapnia; 5% carbon dioxide) and cognitive stimuli. Hypercapnia will require participants to breath a gas containing 5% carbon dioxide and 21% oxygen in a balance of nitrogen gas for 3 minutes following breathing room air for 1 minute prior, via a two-way non-rebreathing valve whilst wearing a nose-clip. The CVR to cognitive stimuli will be assessed during individual cognitive tasks and summated to achieve a total composite CVR to cognitive stimuli. Finger photoplethysmography (human non-invasive blood pressure and haemodynamic monitor) will be used to measure cardiovascular function, with heart rate and arterial blood pressure being measured on a continuous beat-to-beat basis. Participants will complete a validated nutritional questionnaire to estimate energy intake over a typical 24 h period to ensure any changes observed in the primary outcomes are primarily due to the effects of exercise and not changes in nutritional behaviour. Additionally, participants will complete the Profile of Mood States (POMS) questionnaire to calculate total mood disturbance. All measurements, as well as the Yale Physical Activity Survey (YPAS) and POMS, will be repeated 1 week following the completion of the study at a similar time of day to their baseline measurements.

Exercise intervention
Participants allocated to the exercise group will participate in a supervised multimodal exercise program for up to three sessions per week for 8 weeks. The exercise intervention is an established program delivered externally by Accredited Exercise Physiologists at The Fit Lab. It has been adapted from previous research that has validated the safety of exercise interventions in patients with breast cancer (Cormie et al. 2013; Casla et al. 2015). Each session will comprise aerobic exercise and muscle strength training (i.e. multimodal exercise training) and last for approximately 60 min, including a 5 min warm-up and 5 min cool down. Aerobic exercise training will involve, for example, rowing, walking on a treadmill and riding a stationary bike. Examples of muscle strength exercises include chest press, lat pulldown and leg press. These would be expected to be performed at a moderate to vigorous intensity. The exercise session swill be conduction in person in groups of no more than 12 people. The exercise sessions will be self-paced, with progressive overload techniques put in place to ensure exercise capacity and muscle strength progression. An attendance sheet will be used to determine participant compliance to the intervention.
Intervention code [1] 323846 0
Lifestyle
Intervention code [2] 323847 0
Treatment: Other
Comparator / control treatment
The first arm of the study will be the wait-list (control) group, which will not participate in any exercise training, This is quasi-randomised and the control group are comprised of those who are not wishing to participate in exercise at this point in time. Once the study has concluded, the control group will be provided with the exercise regime used in this study. They may enrol in the exercise program offered by Fit Lab at a later date once the study has been completed.
Control group
Active

Outcomes
Primary outcome [1] 331773 0
Cerebrovascular responsiveness to hypercapnia using a transcranial Doppler sonography
Timepoint [1] 331773 0
Pre-intervention and 9 weeks after intervention commencement
Primary outcome [2] 331774 0
Cerebrovascular responsiveness to cognitive stimuli using the NIH Toolbox, Corsi-block sorting test and the trail making task (parts A and B). This will be assessed as a composite primary outcome.
Timepoint [2] 331774 0
Pre-intervention and 9 weeks after intervention commencement
Primary outcome [3] 331775 0
Mean cognitive tests scores using NIH Toolbox battery, Trail Making Task (Parts A & B) and Corsi-block sorting test. This will be assessed as a composite primary outcome.
Timepoint [3] 331775 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [1] 411086 0
Mean profile of mood states score
Timepoint [1] 411086 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [2] 411087 0
Cardiovascular profile (arterial stiffness and blood pressure) using a non-invasive cardiovascular profiler and non-invasive blood pressure (NIBP) system.
Timepoint [2] 411087 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [3] 411088 0
Metabolic, microbiological, inflammatory, haematological and general biochemical markers (serum and plasma). These are exploratory outcomes and will be assessed as a composite secondary outcome.
Timepoint [3] 411088 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [4] 411089 0
Changes in body composition using a Dual-energy X-ray absorptiometry (DEXA). Total fat mass, lean mass, body fat percentage, and bone mineral content and density will be assessed. This will be assessed as a composite secondary outcome.
Timepoint [4] 411089 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [5] 411090 0
Changes in functional capacity (60s sit-to-stand, 400m walk). This will be assessed as a composite secondary outcome.
Timepoint [5] 411090 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [6] 411091 0
Changes in strength testing measurements (chest press, lat pulldown, squat). This will be assessed as a composite secondary outcome.
Timepoint [6] 411091 0
Pre-intervention and 9 weeks after intervention commencement
Secondary outcome [7] 411239 0
The YPAS will be used to ascertain self-reported physical activity status and behaviour.
Timepoint [7] 411239 0
Pre-intervention and 9 weeks after intervention commencement.
Secondary outcome [8] 411240 0
The POMS will be used to ascertain total mood disturbance.
Timepoint [8] 411240 0
Pre-intervention and 9 weeks after intervention commencement.

Eligibility
Key inclusion criteria
Be aged 40-80 years
Female breast cancer patient
Have blood pressure below 160/100mmHg (we will determine this at the screening visit)
Have an adequate ultrasound signal (we will determine this at the screening visit).
Not have heart condition (e.g. congestive heart failure) or a neurological disorder (e.g. stroke)
Minimum age
40 Years
Maximum age
80 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Cognitive impairment and/or dementia
Resting blood pressure equal to or greater than 160/100mmHg
Coronary heart disease
Congestive heart failure
Atrial fibrillation
Prior myocardial infarction
Stroke
Aneurysm
Epilepsy
Multiple sclerosis
Parkinson’s disease
Neuropathies
Presence of a fistulae
Smoker
Middle cerebral artery signal absent on Doppler ultrasound

Study design
Purpose of the study
Treatment
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
Parallel
Other design features
Not applicable
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis
Statistical analyses will be performed using SPSS for Windows or the like thereof. An initial power calculation was performed on the basis of previous research investigating differences in total cognitive capacity between participants undergoing an intervention study. 24 participants will be recruited, which allows for a 20% dropout rate and provides 80% power to detect a significant (P < 0.05) 10% change in total cognitive capacity following exercise training. This was based on a 10% standard deviation observed in previous studies and a medium sized effect (0.8).
Normality of data will be assessed using a Shapiro-Wilk test. Comparisons between groups for baseline characteristics will be determined using an independent t-test or Mann-Whitney U-test for parametric and non-parametric data, respectively. A two-way analysis of variance (ANOVA) will be used to determine the effects of ‘treatment’ (exercise vs. control) and ‘intervention’ (week 0 vs. week 8). Significant interaction effects will be followed by planned pairwise comparisons between groups using the Bonferroni method. Pearson product-moment correlation coefficients or Spearman’s Rho will be calculated to assess the relative percentage change from week 0 to week 8 for the CVR to hypercapnia, total composite CVR to cognitive stimuli and total composite cognitive score in the exercise group for parametric and non-parametric data, respectively. Effect sizes will be determined using Cohen’s d using previously described thresholds (Cohen 1988). Statistical significance will be set at P < 0.05. Results will be presented as means ± SD.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
22/06/2022
Date of last participant enrolment
Anticipated
30/09/2024
Actual
Date of last data collection
Anticipated
23/12/2024
Actual
Sample size
Target
24
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 311686 0
University
Name [1] 311686 0
University of Southern Queensland
Country [1] 311686 0
Australia
Funding source category [2] 313995 0
Charities/Societies/Foundations
Name [2] 313995 0
Blush Cancer Care Inc
Country [2] 313995 0
Australia
Primary sponsor type
University
Name
University of Southern Queensland
Address
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country
Australia
Secondary sponsor category [1] 313141 0
Commercial sector/Industry
Name [1] 313141 0
The Fit Lab Toowoomba
Address [1] 313141 0
Shop 8 / 231 James Street
Toowoomba City QLD 4350
Australia
Country [1] 313141 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311140 0
USQ Human Research Ethics Committee
Ethics committee address [1] 311140 0
Ethics committee country [1] 311140 0
Australia
Date submitted for ethics approval [1] 311140 0
26/04/2022
Approval date [1] 311140 0
14/06/2022
Ethics approval number [1] 311140 0
H22REA103

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120082 0
Dr Edward Bliss
Address 120082 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 120082 0
Australia
Phone 120082 0
+617 46315477
Fax 120082 0
Email 120082 0
[email protected]
Contact person for public queries
Name 120083 0
Edward Bliss
Address 120083 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 120083 0
Australia
Phone 120083 0
+617 46315477
Fax 120083 0
Email 120083 0
[email protected]
Contact person for scientific queries
Name 120084 0
Edward Bliss
Address 120084 0
University of Southern Queensland
West Street
Toowoomba Qld 4350
Australia
Country 120084 0
Australia
Phone 120084 0
+617 46315477
Fax 120084 0
Email 120084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Only data underlying published results collected during the trial will be made available, after de-identification.
When will data be available (start and end dates)?
Immediately following publication of any journal articles that are generated throughout the course of the study. No end date
Available to whom?
Individual data will also be available to the participants of the study on request.
De-identified data will be available for journal/conference proceedings.
Researchers on the project (i.e. co-investigators)
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Restricted access via USQ data portal (password protected) and this will be granted subject to approvals by Principal Investigator ([email protected]).


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
No additional documents have been identified.