Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001548729
Ethics application status
Approved
Date submitted
12/10/2022
Date registered
14/12/2022
Date last updated
9/05/2024
Date data sharing statement initially provided
14/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Cognitive decline in cancer: Investigating a brain training intervention
Scientific title
Cancer-related cognitive impairment: Investigating the impact of a brain training intervention on cognition, psychosocial factors, and neurogenesis biomarkers
Secondary ID [1] 307992 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12622001537741p

This study is a cross-sectional observation study, from which the participants for the current study will be recruited. The data from the cross-section will also serve as baselines for assessing interventional efficacy.

Health condition
Health condition(s) or problem(s) studied:
cancer 327652 0
cancer-related cognitive impairment (CRCI) 327653 0
cancer psychosocial distress 327654 0
neurodegenerative disorders 327655 0
Condition category
Condition code
Neurological 324741 324741 0 0
Neurodegenerative diseases
Cancer 324742 324742 0 0
Any cancer
Physical Medicine / Rehabilitation 325189 325189 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: cognitive training

Variables collected include cognitive performance, psychosocial functioning, medical history, and peripheral plasma brain-derived neurotrophic factor (BDNF) levels.

This study entails a double blinded randomised control trial, evaluating the efficacy of a cognitive training intervention in treating cancer-related cognitive impairment (CRCI). The doctoral candidate is blinded to the intervention/control groups. Cognitive training is theorised to work by stimulating neuroplasticity - a process intricately linked with neurogenesis.


The intervention used in the RCT will be a computerised cognitive training intervention (Cognifit) which will be administered at home, through participants' personal hardware (computer, phone, tablet). The procedure for participants entails completing brain training tasks. The task difficulty will be tailored by the programme software to each individual participant, in order to be sufficiently challenging but not overwhelming. This is to facilitate yield of optimal cognitive benefit. The tailoring of the difficulty is done automatically by the programme throughout each training session. The control group participants will be receiving a placebo/active control, which are cognitive activities that do not target proposed impaired domains of cognition (i.e., memory, attention, executive function, and processing speed). The process, administration, delivery, location etc. will mirror the intervention group.

Cognitive training tasks include (but are not limited to): puzzles, games, word problems. The cognitive training will be a global battery of tasks, with stimulated domains including (but not limited to) memory, attention, executive function, and processing speed.

This intervention is self-administered with reminders. The doctoral candidate leading the study will provide information on use to participants. Each participant will follow their own timeline. The intervention will be delivered across six weeks, with a minimum of four administrations per week; each session will be a minimum of 20 minutes.

To clarify, the base requirement is that participants must complete a minimum of 120 minutes of training per week - i.e., 720 minutes / 12 hours of training across the six weeks. The additional requirements are that the weekly 120 minutes must be completed across four or more training sessions, and each session should be a minimum of 20 minutes. However, note that four sessions of 20 minutes do not actually meet the minimum weekly 120 minutes - they merely form the minimum training parameters. The actual duration of each session will depend on total weekly number of sessions. This can be done multiple ways. Some possible examples include (but are not limited to):
o 4 x 30 min = 120 min
o 6 x 20 min = 120 min
o 3 x 20 min + 2 x 30 min = 120 min
o 2 x 20 min + 2 x 25 min + 1 x 30 min = 120 min

There is no maximum amount of training. Each participant will be asked to complete the training in their own home at whichever times best suit them, so long as the minimum 12 hours of training is achieved, in the required weekly increments.

Additionally, a CogniFit General Cognitive Assessment (30 min) will be completed at the start and end of the six weeks; this is an in house tool is required for the programme to calibrate and evaluate the participants' training.

Intervention adherence and fidelity will be assessed by the doctoral candidate. The daily reminders will help minimise attrition.

At the end of this six-week trial, participants will attend a follow-up assessment (90-120 min), mirroring the appointment at the baseline. Ideally, this follow-up will be conducted within one week of completing cognitive training.
Intervention code [1] 324563 0
Treatment: Other
Comparator / control treatment
As the study is a double blinded RCT, the control group participants will be receiving an active control, which are cognitive activities that do not target proposed impaired domains of cognition in CRCI (i.e., memory, attention, executive function, and processing speed).

The materials, process, administration, delivery, location etc. will mirror the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 332707 0
Changes in verbal memory, as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R).
Timepoint [1] 332707 0
Baseline; within 7 days post-completion of intervention (primary); and, if possible, a 3-month follow-up post-completion of intervention.
Primary outcome [2] 332708 0
Changes in peripheral BDNF levels, as measured by plasma assays.
Timepoint [2] 332708 0
Baseline; within 7 days post-completion of intervention (primary); and, if possible, a 3-month follow-up post-completion of intervention.
Primary outcome [3] 333321 0
Changes in attention / executive functioning, as assessed by the Trail Making Test (TMT).
Timepoint [3] 333321 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [1] 414443 0
Changes in verbal fluency, as assessed by the Controlled Oral Word Association Test (COWAT) of the Multilingual Aphasia Examination.
Timepoint [1] 414443 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [2] 414444 0
Changes in auditory information processing speed, as assessed by the Paced Auditory Serial Addition Test (PASAT).
Timepoint [2] 414444 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [3] 414463 0
Changes in perceived cancer-related cognitive impairment, as assessed by the Functional Assessment of Cancer Therapy - Cognition (FACT-Cog).
Timepoint [3] 414463 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [4] 414466 0
Changes in depressive symptoms, as assessed by the Patient Health Questionnaire-9 (PHQ-9).
Timepoint [4] 414466 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [5] 414467 0
Changes in anxiety symptoms, as assessed by the General Anxiety Disorder-7 (GAD-7).
Timepoint [5] 414467 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [6] 414468 0
Changes in sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PSQI).
Timepoint [6] 414468 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [7] 414469 0
Changes in experienced pain severity, as assessed by the McGill Pain Questionnaire - Short Form (MPQ-SF).
Timepoint [7] 414469 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [8] 414470 0
Changes in self-efficacy, as assessed by the New General Self-Efficacy Scale (NGSE).
Timepoint [8] 414470 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [9] 414471 0
Changes in quality of life / subjective well-being, as assessed by the McGill Quality of Life Questionnaire - Expanded (MQOL-E).
Timepoint [9] 414471 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [10] 414472 0
Changes in death anxiety, as assessed by the Death and Dying Distress Scale (DADDS).
Timepoint [10] 414472 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [11] 414473 0
Changes in morale levels, as assessed by the Demoralisation Scale-II (DS-II).
Timepoint [11] 414473 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [12] 414475 0
Medical history, including, but not limited to: tumour details, treatment regimen, current medication, and comorbidities/premorbidities, menopausal. Assessed through obtaining medical history and direct questioning.
Timepoint [12] 414475 0
Full assessment at baseline. Then checking with participant to see if anything changed post intervention completion - within 7 days and at three month follow-up.
Secondary outcome [13] 414476 0
Lifestyle factors, such as exercise habits, weekly alcohol consumption, use of tobacco, recreational substance use. Assessed through self-report.
Timepoint [13] 414476 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [14] 415931 0
Changes in working memory, as assessed by the Stroop test.
Timepoint [14] 415931 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.
Secondary outcome [15] 434854 0
Therapeutic Framework of Acceptability - Adapted for Cognitive Training in Cancer Patients
Timepoint [15] 434854 0
Secondary outcome [16] 434855 0
Therapeutic Framework of Acceptability - Adapted for Cognitive Training in Cancer Patients
Timepoint [16] 434855 0
Baseline; within 7 days post-completion of intervention; and, if possible, a 3-month follow-up post-completion of intervention.

Eligibility
Key inclusion criteria
From baseline, study inclusion criteria require participants to be aged over 18 years old, currently live in Perth and Peel regions of Western Australia (or close enough), have been diagnosed with non-CNS cancer, be currently undergoing any treatment, and have a working proficiency of the English language.

Participants invited to take part in the RCT will have cancer, access to and ability to use a phone/tablet/computer with internet for six weeks, and will demonstrate cognitive impairment, operationalised by scores meeting one or more of the following criteria (Vardy et al., 2007; Wefel et al., 2011): scores = 1.0SD below the norm on two or more objective cognitive measures; or score of = 1.5SD below the norm on one or more objective cognitive measures; Global Deficit Score (GDS) = 0.5 points. GDS = mean of deficit scores (which are converted from T scores). A GDS of 0.5 or greater indicates the mean of the objective cognitive measure scores is = 1SD below the norm. Note that “norm” means demographic matched normative scores from neuropsychological compendium.

If necessitated, subjective impairment will also be considered; evidence thereof will be identified through FACT-Cog Perceived Cognitive Impairment (18-item) subscale scores < 54 (Dyk et al., 2020).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
From baseline, exclusion criteria preclude participation of individuals with premorbid developmental / cognitive dysfunction; premorbid neurodegenerative conditions; pregnancy; and central nervous system metastases.

Inverse of the baseline inclusion criteria, participants not demonstrating cognitive impairment are not invited to the RCT.

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 concealment will be conducted through central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation will be conducted through computerised randomisation table.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
80-100 cancer patients are planned to be recruited for the RCT.

To disentangle the complex relationships within CRCI, meta-analyses advocate for sophisticated statistical modelling and machine learning (Santos & Pyter, 2018; Seigers & Fardell, 2011; Wefel et al., 2015). As such, the proposed research will conduct three different algorithms for the main analysis, and the model that most validly represents the data for each study will be selected. It is not uncommon to test models against each other in machine learning research; this method has also been adopted by CRCI studies (e.g., Zhou et al., 2021). The proposed models are random forest regression (RFR), support vector machine (SVM), and least absolute shrinkage and selection operator (LASSO) logistic regression. To provide comparative benchmarks, basic logistic/hierarchical regressions will be run with variables mirroring the ones evinced as significant by the machine learning counterparts. The predictive utility of the machine learning models will be assessed by comparing error rate when testing the validation sample, as well as percentage of variance accounted for in outcome variable. The training/validation split will be the conventional 80/20. Treatment efficacy will be assessed simply with a within subjects t-test or Mann-Whitney U-test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/05/2023
Actual
14/12/2023
Date of last participant enrolment
Anticipated
10/01/2025
Actual
Date of last data collection
Anticipated
7/03/2025
Actual
Sample size
Target
100
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 312254 0
University
Name [1] 312254 0
Curtin University
Country [1] 312254 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Kent St, Bentley 6102, Western Australia
Country
Australia
Secondary sponsor category [1] 313796 0
None
Name [1] 313796 0
Address [1] 313796 0
Country [1] 313796 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311781 0
Curtin Human Research Ethics Committee
Ethics committee address [1] 311781 0
Ethics committee country [1] 311781 0
Australia
Date submitted for ethics approval [1] 311781 0
18/07/2023
Approval date [1] 311781 0
16/10/2023
Ethics approval number [1] 311781 0
HRE2023-0599

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

Contacts
Principal investigator
Name 121782 0
Mr Siddharth Ganesh
Address 121782 0
Curtin University, Kent St, Bentley WA 6102
Country 121782 0
Australia
Phone 121782 0
+61 406659735
Fax 121782 0
Email 121782 0
[email protected]
Contact person for public queries
Name 121783 0
Siddharth Ganesh
Address 121783 0
Curtin University, Kent St, Bentley WA 6102
Country 121783 0
Australia
Phone 121783 0
+61 493105286
Fax 121783 0
Email 121783 0
[email protected]
Contact person for scientific queries
Name 121784 0
Siddharth Ganesh
Address 121784 0
Curtin University, Kent St, Bentley WA 6102
Country 121784 0
Australia
Phone 121784 0
+61 406659735
Fax 121784 0
Email 121784 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?
Scores on cognitive and psychosocial measures; deidentified medical and demographic information; neurogenesis biomarkers data. Subsequent analyses will be made public as well.

None of this data will be identifiable.
When will data be available (start and end dates)?
Once data is obtained - no end date.
Available to whom?
Only future researchers who provide a methodologically sound proposal, at the discretion of the primary investigators and Curtin University.
Available for what types of analyses?
Meta-analyses / systematic reviews, machine learning research, CRCI research.
How or where can data be obtained?
Yet to be determined, but will need to contact primary investigators.

Siddharth Ganesh
[email protected]


What supporting documents are/will be available?




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.