Please note the ANZCTR will be unattended from Friday 20 December 2019 for the holidays. The Registry will re-open on Tuesday 07 January 2020. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR


Registration number
ACTRN12618000750280
Ethics application status
Approved
Date submitted
6/04/2018
Date registered
4/05/2018
Date last updated
11/12/2019
Date data sharing statement initially provided
22/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effect of Cognitive and Exercise Training on Cognition in Breast Cancer Patients Receiving Chemotherapy.
Scientific title
The Effect of Cognitive and Exercise Training on Cognitive Decline in Breast Cancer Patients Treated with Adjuvant Chemotherapy Agents
Secondary ID [1] 294234 0
None
Universal Trial Number (UTN)
U1111-1210-3035
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 306905 0
Condition category
Condition code
Cancer 305997 305997 0 0
Breast
Physical Medicine / Rehabilitation 306044 306044 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-blind (assessor blind to group allocation), two-arm (cognitive and exercise training versus usual care), randomized controlled phase 1 trial. This trial will examine the feasibility, safety and therapeutic benefits of cognitive and exercise training, compared to usual care, in stage I-III breast cancer patients treated with chemotherapy agents.

Participants will be randomly assigned to cognitive and exercise training and usual care groups by an independent biostatistician. Participants in both groups will receive 12 weeks of treatment (cognitive and exercise training / usual care).

The cognitive and exercise training program comprises three times weekly periodised aerobic and resistance exercise and computerized cognitive training for 90 minutes. All training sessions will be conducted in groups of 4-5 patients.

The cognitive training component of the intervention is informed by our previous work in healthy and neurodegenerative populations. This fully-personalised program uses a series of algorithms developed by Dr Amit Lampit (Co-PI) to adapt training difficulty and content to individual cognitive profiles. Thirty-five exercises covering subdomains of memory, planning, processing speed, inhibition and attention impairments, which are compromised in breast cancer patients, will be delivered by NeuroNation software (Berlin). The program will run via a secure research server in Perth. In line with Dr Amit Lampit’s findings regarding cognitive training settings and dose, as well as our pilot results, participants will be required to engage in the cognitive training program three times per week for 45 minutes per session in a supervised group setting in exercise clinics. Training sessions will be delivered by exercise physiologists who will follow a procedures manual. Training data will be recorded by the research server and used to analyse the association between cognitive training engagement and clinical response across individuals.

The exercise training component of the intervention is informed by our previous work and includes aerobic and resistance exercise using ergometers, free weights and machine weights. The intensity and volume of training will be set based on a baseline cardiopulmonary exercise test and muscle strength tests. Throughout the intervention the intensity and volume of training will be systematically changed using an linear periodisation protocol developed by our team. Heart rate peak, and rating of perceived exertion (RPE) during training sessions will be recorded with heart rate monitors and the Borg RPE scale and used to inform adjustments to training intensity and volume throughout the intervention. Exercise training will be delivered in a group format three times per week for 45 minutes by exercise physiologists using a standardised procedures manual to ensure the consistency of delivery. Changes in exercise performance (exercise and session RPE, total training volume, 1RM data) will be recorded by exercise physiologists.
Intervention code [1] 300528 0
Rehabilitation
Intervention code [2] 300902 0
Treatment: Other
Comparator / control treatment
The prospective trial includes a usual care control group. Patients allocated to this group will be asked to maintain their current activities of daily living. Following the trial, the control group will be provided with details of the cognitive and exercise training intervention.
Control group
Active

Outcomes
Primary outcome [1] 305033 0
Feasibility of cognitive and exercise training and usual care for breast cancer patients treated with chemotherapy agents.

Feasibility will be measured by evaluating the recruitment and retention of breast cancer patients during the trial, as well as the adherence of breast cancer patients to cognitive and exercise training and usual care. The recruitment (number of patients recruited) and retention (number of patient dropouts) of breast cancer patients during the trial will be recorded by the chief principle investigator. Adherence to cognitive and exercise training and usual care throughout the trial will be recorded by exercise physiologists.
Timepoint [1] 305033 0
The feasibility of cognitive and exercise training and usual care will be measured throughout the entirety of the trial.
Primary outcome [2] 305065 0
Safety of cognitive and exercise training

The safety of cognitive and exercise training will be examined by evaluating adverse events, including musculoskeletal injury, cardiovascular events, falls, excessive mental and physical fatigue. Adverse events reported by patients will be recorded by exercise physiologists.
Timepoint [2] 305065 0
The safety of cognitive and exercise training (adverse events and exercise tolerance) will be recorded for each training session for patients.
Primary outcome [3] 305520 0
Exercise Tolerance

Exercise tolerance will be measured using visual analog scales (VAS, 0-10); and by recording the rating of perceived exertion (RPE; Borg Scale, 0-10) after each exercise session. Exercise tolerance will be recorded by exercise physiologists.
Timepoint [3] 305520 0
Exercise Tolerance will be recorded for each training session for patients.
Secondary outcome [1] 343952 0
Verbal learning and memory

Verbal learning and memory will be evaluated using the Hopkins Verbal Learning Test-Revised. This is a composite outcome.
Timepoint [1] 343952 0
Verbal learning and memory will be examined with the Hopkins Verbal Learning Test-Revised before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [2] 343967 0
Aerobic fitness

Aerobic fitness will be examined using a standardized cardiopulmonary exercise test, 6-minute walk test and 400 m walk test.
Timepoint [2] 343967 0
Cardiopulmonary fitness will be examined before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of cognitive and exercise training.
Secondary outcome [3] 343968 0
Habitual Sleep

The Consensus Sleep Diary
Timepoint [3] 343968 0
Habitual sleep will be examined with the consensus sleep diary before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [4] 344053 0
Muscle Strength

Muscle strength will be measured in the upper and lower extremities using one repetition maximum (1RM) and six repetition maximum (1RM) strength tests .
Timepoint [4] 344053 0
Muscle strength will be examined before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of cognitive and exercise training
Secondary outcome [5] 344054 0
Anxiety and Depression

Anxiety and depression symptoms will be evaluated using the Hospital Anxiety and Depression Scale, This is a composite outcome.
Timepoint [5] 344054 0
Anxiety and Depression will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [6] 344055 0
Psychological Stress

Psychological stress will be evaluated using the Perceived Stress Scale.
Timepoint [6] 344055 0
Psychological stress will be examined with the Perceived Stress Scale before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [7] 344056 0
Fatigue

Fatigue will be examined using the Brief Fatigue Inventory.
Timepoint [7] 344056 0
Fatigue will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [8] 344057 0
Physical Activity

Physical activity will be evaluated using the Minnesota Leisure Time Physical Activity Questionnaire.
Timepoint [8] 344057 0
Physical activity will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [9] 344058 0
Social Network Size and Complexity

The Social Network Index (SNI) will be used to examine social network size and complexity.

This is a composite outcome.
Timepoint [9] 344058 0
Social network size and complexity will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [10] 344060 0
Premorbid Intelligence

The National Adult Reading Test will be used to examine premorbid intelligence.
Timepoint [10] 344060 0
Premorbid Intelligence will be evaluated before surgery.
Secondary outcome [11] 344061 0
Cognitive Leisure

Cognitive Leisure will be examined using the Cognitive Leisure Scale developed by Wilson et al (1999, 2000).
Timepoint [11] 344061 0
Cognitive leisure will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [12] 344064 0
Education and Occupation History/Complexity

Education and occupational history/complexity will be evaluated using a customized demographic questionnaire.

This is a composite outcome/Questionnaire.
Timepoint [12] 344064 0
Education and occupation history/complexity will be evaluated before surgery.
Secondary outcome [13] 344066 0
Quality of life

Health-related quality of life outcomes for general health, pain, vitality, social functioning and mental health will be evaluated using the Short Form 36 survey.
Timepoint [13] 344066 0
Health-related quality of life will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [14] 344069 0
Waist Circumference

Waist circumference are defined as the mid-point between the 10th rib and iliac crest.
Timepoint [14] 344069 0
Waist circumference will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [15] 344070 0
Hip Circumference

Hip circumferences are defined as the level of the greater trochanter for both limbs.
Timepoint [15] 344070 0
Hip circumference will be examined before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [16] 344186 0
Blood sampling

30mL of blood will be drawn from study participants for the exploratory analysis of biological markers associated with cancer related cognitive impairments. This is an exploratory outcome.
Timepoint [16] 344186 0
Blood will be sampled before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [17] 345576 0
Habitual Sleep

Pittsburgh Sleep Quality Index
Timepoint [17] 345576 0
Habitual sleep will be examined with the Pittsburgh Sleep Quality Index before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [18] 345577 0
Circadian Rhythm and Habitual Sleep

7 Day Wrist-Worn Actigraphy
Timepoint [18] 345577 0
Circadian Rhythm and Habitual Sleep will be examined with the 7 day wrist-worn actigraphy before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [19] 345578 0
Habitual Sleep/Sleep Quality

Epworth Sleepiness Scale
Timepoint [19] 345578 0
Habitual Sleep/Sleep Quality will be examined with the the Epworth Sleepiness Scale before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [20] 346255 0
Health related quality of life


The EORTC-QLQ-30 will also be used to measure specific indices of quality of life. The EORTC-QLQ-30 was specifically designed to examine health-related quality of life in cancer patients.
Timepoint [20] 346255 0
Health related quality of life will be examined with the EORTC-QLQ-30 before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [21] 346256 0
Psychological Stress

Psychological stress will be evaluated using the Brief Symptom Inventory (BSI-18).
Timepoint [21] 346256 0
Psychological stress will be examined with the Brief Symptom Inventory (BSI-18) before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [22] 346257 0
Attention, visual scanning and cognitive flexibility

Attention, visual scanning and cognitive flexibility will be examined with the Trail Making Test. This is a composite outcome.
Timepoint [22] 346257 0
Attention, visual scanning and cognitive flexibility will be examined with the Trial Making Test before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [23] 346258 0
Processing speed


Processing speed will be examined using the Symbol Digit Modalities Test
Timepoint [23] 346258 0
Processing speed will be examined with the Symbol Digit Modalities Test before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [24] 346259 0
Executive function


Executive function will be examined with the Rey Complex Figure Test.
Timepoint [24] 346259 0
Executive function will be examined with the Rey Complex Figure Test before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [25] 346260 0
Cognitive dual tasking


Cognitive dual tasking will be evaluated using a progressive subtraction test.
Timepoint [25] 346260 0
Cognitive dual tasking will be examined with progressive subtraction tests before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [26] 346261 0
Social cognition


Social cognition will be evaluated using the Reading The Mind in The Eyes Test.
Timepoint [26] 346261 0
Social cognition will be examined with the Reading The Mind in The Eyes Test before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [27] 346262 0
Social Cognition


Social cognition will be evaluated using the Mini-SEA.
Timepoint [27] 346262 0
Social cognition will be examined with the Mini-SEA before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [28] 346263 0
Emotion Recognition


Emotion recognition will be evaluated using the Cambridge Faces Test.
Timepoint [28] 346263 0
Emotion recognition will be examined with the Cambridge Faces Test before surgery, after surgery/before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and after the completion of cognitive and exercise training.
Secondary outcome [29] 377879 0
Beliefs and attitudes about sleep

Beliefs and attitudes about sleep will be evaluated using the Dysfunctional Beliefs and Attitudes About Sleep Scale.
Timepoint [29] 377879 0
Beliefs and attitudes about sleep will be evaluated using the Dysfunctional Beliefs and Attitudes About Sleep Scale before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of the cognitive and exercise training.
Secondary outcome [30] 377880 0
Sleep Effort

Sleep effort will be evaluated using the Glasgow Sleep Effort Scale.
Timepoint [30] 377880 0
Sleep effort will be evaluated using the Glasgow Sleep Effort Scale before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of the cognitive and exercise training.
Secondary outcome [31] 377881 0
Insomnia

Insomnia will be evaluated using the Insomnia Severity Index.
Timepoint [31] 377881 0
Insomnia will be evaluated using the Insomnia Severity Index before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of the cognitive and exercise training.
Secondary outcome [32] 377882 0
Circadian Rhythm

Circadian Rhythm will be evaluated using the Morningness and Eveningness Scale.
Timepoint [32] 377882 0
Circadian Rhythm will be evaluated using the Morningness and Eveningness Scale before the commencement of chemotherapy, after chemotherapy/before the commencement of the cognitive and exercise training and upon completion of the cognitive and exercise training.

Eligibility
Key inclusion criteria
Inclusion criteria include: 1) patients with stage I-III breast cancer prior to first line treatment, 2) patients that will receive adjuvant anthracycline, alkylating, antimetabolite and taxane chemotherapy agents, and 3) patients capable of providing written and informed consent.
Minimum age
21 Years
Maximum age
80 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include: 1) patients with brain metastases, and 2) patients with concomitant neurological, cardiovascular, and psychological conditions, and 3) patients unable to engage in cognitive and exercise training.

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)
Participants will be randomly allocated to cognitive and exercise training or usual care treatment groups by an independent biostatistician. All assessors will be blinded to group allocation. The biostatistician responsible for analysing the data will also be blinded to group allocation. The exercise physiologist administering the cognitive and exercise training will not be blinded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization stratified by age and medical treatment. Randomization ratio of 1:1 (cognitive and exercise training to usual care)
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)
Safety/efficacy
Statistical methods / analysis
Data will be assessed using SPSS (IBM Corporation, Chicago, IL, USA) and R statistical software. Linear mixed modeling will be used to examine changes in primary and secondary outcomes over time. All analyses will be conducted in an intention-to-treat manner.

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)
WA
Recruitment hospital [1] 10262 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 21928 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 298873 0
Charities/Societies/Foundations
Name [1] 298873 0
Cancer Council WA
Address [1] 298873 0
420 Bagot Road, Subiaco 6008, Perth, Western Australia
Country [1] 298873 0
Australia
Primary sponsor type
University
Name
Edith Cowan University
Address
Exercise Medicine Research Institute
Edith Cowan University
270 Joondalup Drive
Joondalup, WA 6027
Country
Australia
Secondary sponsor category [1] 298084 0
None
Name [1] 298084 0
Address [1] 298084 0
Country [1] 298084 0
Other collaborator category [1] 279989 0
Hospital
Name [1] 279989 0
Fiona Stanley Hospital
Address [1] 279989 0
11 Robin Warren Drive, Murdoch, 6150 Western Australia
Country [1] 279989 0
Australia
Other collaborator category [2] 279990 0
University
Name [2] 279990 0
University of Western Australia
Address [2] 279990 0
35 Stirling Hwy, Crawley, 6009, Western Australia
Country [2] 279990 0
Australia
Other collaborator category [3] 279991 0
University
Name [3] 279991 0
University of Melbourne
Address [3] 279991 0
The University of Melbourne, Victoria, 3010
Country [3] 279991 0
Australia
Other collaborator category [4] 279992 0
University
Name [4] 279992 0
German Sports University
Address [4] 279992 0
Am Sportpark Müngersdorf 6, 50933 Köln, Germany
Country [4] 279992 0
Germany

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299814 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 299814 0
11 Robin Warren Dr, Murdoch WA 6150
Ethics committee country [1] 299814 0
Australia
Date submitted for ethics approval [1] 299814 0
29/08/2018
Approval date [1] 299814 0
10/01/2019
Ethics approval number [1] 299814 0
Ethics committee name [2] 299816 0
Edith Cowan University Human Research Ethics Committee
Ethics committee address [2] 299816 0
270 Joondalup Drive, Joondalup, 6027, Western Australia
Ethics committee country [2] 299816 0
Australia
Date submitted for ethics approval [2] 299816 0
31/05/2018
Approval date [2] 299816 0
Ethics approval number [2] 299816 0

Summary
Brief summary
Study Aims
This study aims to assess the impact of a cognitive and exercise training (CET) program on cognition in breast cancer patients.

Who is it for?
You may be eligible to participate in this study if you are aged 21 years or older, have been diagnosed with Stage I-III breast cancer and are scheduled to receive chemotherapy treatment.

Study details
Participants will be randomly assigned (by chance) to receive either the cognitive & exercise training (CET) program, or continue with standard care. Those in the CET group will undergo 3 x 90 minute sessions per week for 12 weeks. The standard care group will be provided with details of the CET intervention after the 12 week period. All participants will undergo a series of diagnostic and clinical tests, including blood tests, fitness and cognitive tests, sleep tests and questionnaires.

Potential study outcomes
It is hoped this research will inform the treatment of breast cancer patients presenting with detrimental cognitive changes as a result of chemotherapy, and this research may lead to better quality of life for patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81650 0
Dr Travis Cruickshank
Address 81650 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 81650 0
Australia
Phone 81650 0
+61 8 6304 3416
Fax 81650 0
Email 81650 0
t.cruickshank@ecu.edu.au
Contact person for public queries
Name 81651 0
Dr Travis Cruickshank
Address 81651 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 81651 0
Australia
Phone 81651 0
+61 8 6304 3416
Fax 81651 0
Email 81651 0
t.cruickshank@ecu.edu.au
Contact person for scientific queries
Name 81652 0
Dr Travis Cruickshank
Address 81652 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 81652 0
Australia
Phone 81652 0
+61 8 6304 3416
Fax 81652 0
Email 81652 0
t.cruickshank@ecu.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
Data for this study will be kept confidential in a re-identifiable format. The identifier code will only be available to study investigators. Group data will only be presented at conferences and in publications
What supporting documents are/will be available?
No other documents available
Summary results
No Results