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Trial registered on ANZCTR


Registration number
ACTRN12618000799257
Ethics application status
Approved
Date submitted
9/05/2018
Date registered
10/05/2018
Date last updated
1/10/2019
Date data sharing statement initially provided
9/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of cognitive training on cognitive outcomes following coronary artery bypass grafting surgery in older adults.
Scientific title
Reducing delirium and dementia risk: A cognitive training intervention of older adults undergoing elective coronary artery bypass grafting surgery.
Secondary ID [1] 294821 0
NMHRC Boosting Dementia Research Leadership Fellowship- GNT 1135676
Secondary ID [2] 294835 0
Heart Foundation Vanguard Grant- 101758
Universal Trial Number (UTN)
U1111-1213-7811
Trial acronym
The Cognitive CABG Study, CCABG
Linked study record
NA

Health condition
Health condition(s) or problem(s) studied:
Cognition 307751 0
Delirium 307752 0
Condition category
Condition code
Neurological 306807 306807 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The HappyNeuron Pro cognitive training platform will be utilised to deliver the cognitive training within the study. There will be two cognitive training intervention time points throughout the study. The first is pre-surgery, starting immediately after completing their baseline session, and involve approximately 2 weeks of training. The second intervention will begin 1-month after the participant has had their surgery and will involve 12 weeks of cognitive training. The same participants who complete pre-surgery cognitive training will complete post-surgery intervention. The cognitive training intervention will be in addition to normal care pre and post-surgery, and the intervention will be conducted outside of any needed hospital visits so not to disrupt normal care.
Within the cognitive training program, each session has been planned and is identical across participants (each session equally trains targeted domains; pyscho-motor speed, attention, memory and executive function). However, the program is still personalised as each exercise has 9 levels and allows participants to level up through the exercises at different rates (consistent high performance increases the level, consistent low performance results in levelling down).
For participants randomised into the cognitive training, the training intervention will be home-based and conducted on either a participant’s personal laptop or on a supplied University laptop. The duration of the sessions will be 45 minutes of completed cognitive training (if break wanted/needed then extend session. E.g. 3 minute break; session extends to 48 minutes). The session frequency pre-surgery will be every other day (3.5 times a week), post-surgery this frequency will be decreased to 3 times a week.
Pre-surgery cognitive training: The initial session will be instructed and supervised, with an emphasis being placed on participant understanding and competence of system use. Participants will complete 45 minutes of cognitive training every other day over a two week period following baseline testing (total of approximately 7 sessions).

Post-surgery cognitive training: This second program will last for a longer duration (compared to pre-surgery) of 12 weeks. Between their pre- and post-surgery interventions participants will be prohibited from using their cognitive training log in. The initial session will yet again be supervised. The post-surgery intervention will be conducted for twelve weeks with 45 minute sessions three times a week (total of 27 hours). Following the completion of the intervention, participants will be informed and prohibited from using the cognitive training system until the commencement of the final follow-up session (3 years post-surgery).

To support participants with their cognitive training and to help with adherence, multiple strategies have been put in place. Firstly weekly, face-to-face interventions will be offered to the participants to support any person who may be having difficulties. If individual participants require further support, multiple face-to-face sessions/ phone calls or other support will be organised. Weekly phone calls will also be made to check in on participants, and allow them to ask any questions. An instruction booklet will be provided to participants with information of how to use the program and outline technical troubleshooting. Within the booklet contact information of the cognitive training members of the research team is provided for any further questions. The members of the research team have been trained by Dr Amit Lampit, a cognitive training expert with experience in running large cognitive training interventions.
Intervention code [1] 301134 0
Prevention
Comparator / control treatment
Participants who are not randomised into cognitive training will not receive any form of cognitive training and will receive normal care. Normal care pre and post-surgery may include doctors appointments, information sessions regarding surgery and out-patient rehabilitation. These participants will still be contacted throughout the research process for data collection.
Control group
Active

Outcomes
Primary outcome [1] 305799 0
Cognition
Measured by the Addenbrookes Cognitive Examination-III and a 5 assessment battery on the CANTAB system (MOT, RTI, PAL, SWM and OTS).
Timepoint [1] 305799 0
Baseline (2 weeks prior to surgery), Discharge (day after discharge), 4-months post-surgery [Primary Timepoint], 6-months post-surgery, 12-months post-surgery and 3 years post-surgery
Primary outcome [2] 305800 0
Delirium
Measured in ICU (CAM-ICU and RASS)
Measured in ward (MDAS, OSLA and CAM)
Weekends, chart based review delirium method conducted on Monday (data for Saturday and Sundays)
Timepoint [2] 305800 0
In hospital, in ICU (daily until moved to ward) and daily within ward until discharge. Additional day after discharge measure during discharge assessment [Primary Timepoint].
Secondary outcome [1] 346621 0
Depression measured by Geriatric Depression Scale: short form
Timepoint [1] 346621 0
Baseline (2 weeks prior to surgery), Discharge (day after discharge), 4-months post-surgery, 6-months post-surgery, 12-months post-surgery and 3 years post-surgery
Secondary outcome [2] 346661 0
Dementia Risk measured with the Australian National University - Alzheimer’s Disease Risk Index (ANU-ADRI)
Timepoint [2] 346661 0
Baseline (2 weeks prior to surgery), 6-months post-surgery, 12-months post-surgery and 3 years post-surgery
Secondary outcome [3] 346662 0
Disability measured with the World Health Organisation Disability Assessment Schedule 2.0 -WHODAS 2.0 12-item
Timepoint [3] 346662 0
Baseline (2 weeks prior to surgery), 6-months post-surgery, 12-months post-surgery and 3 years post-surgery
Secondary outcome [4] 346663 0
Quality of Life measured with the World Health Organisation Quality of Life Brief Questionnaire- WHOQOL-BREF
Timepoint [4] 346663 0
Baseline (2 weeks prior to surgery), 6-months post-surgery, 12-months post-surgery and 3 years post-surgery

Eligibility
Key inclusion criteria
Persons must be undergoing elective CABG surgery at the Royal Adelaide Hospital aged 65 years and over. Must be proficient English speakers, have normal vision and hearing with or without the use of aids, live within metropolitan boundaries of Adelaide (Development Act 1993) and be willing to participate in a longitudinal study with follow-up sessions.
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known learning disabilities or dementia diagnosis, a significant neurological/ psychiatric diagnosis (all factors will affect ability to perform assessments)
* History of cancer treatment within the past 5 years (excluding pure surgical treatment) [as cancer treatment is known to negatively affect cognition ]).
* Suffered a stroke within the past year (many stroke related cognitive impairments subside within a year)
* Currently practicing cognitive training (will interfere or muddle cognitive training effects).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Recruitment will take place at the Royal Adelaide Hospital during pre-surgery clinic day by the Lead investigator. Randomisation into either control or intervention will take place during the baseline session conducted the day following pre-surgery clinic day by research assistants. The randomisation list was established prior to the enrollment of the first participant. Participants will be give an sequential ID number (by order of recruitment), this number will indicate which study group they will enrolled in according to the randomisation sheet.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence was generated prior to the enrollment of the first participant.
The randomisation was generated utilising computer software ensuring even numbers would be allocated to each group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Utilising G*power statistical analysis software, a priori sample size was calculated based on a published meta-analysis effect size (Hedges' g=.35) of the overall effect of CCT on cognitive outcomes (in adults 60 years and older who presented with mild cognitive-impairment). This power analysis is based on the primary study outcomes; presence of cognitive decline at 4-month follow-up and delirium presence following surgery. Utilising g=.35, power=.80 and a=.05, the computed sufficient sample size for comparing presence vs absence of delirium or cognitive decline utilising logistic regression was n= 94 (47 per group); therefore, in order to account for participant attrition during follow-up a total of n=120 (60 per group) participants will be recruited.

To determine the cognitive effects of CCT on delirium incidence and cognitive decline post-CABG, a per-protocol analysis method will be employed; where only data from participants who completed greater than or equal to 66% of prescribed CCT will be included in the primary analyses (not applicable to control group). For our primary analyses (delirium: delirium presence, and cognitive decline: 4 months) we will therefore only include participants without missing data. For all analyses, effect sizes will be reported and discussed.

Primary and secondary outcomes
Delirium: Delirium (presence vs absence across hospital stay) will be the outcome variable in a logistic regression, with group membership (control v intervention) as a predictor variable, and age and gender as covariates.

Cognitive decline: Cognitive decline will be calculated using the reliable change index (RCI) method, across the four CANTAB tests (main outcome measure will be utilised for RTI, PAL, SWM, OTS). The RCI method reflects individual change, between two timepoints (baseline to follow-up time-point), relative to whole sample data whilst considering practice effects of the test. Significant cognitive decline of an individual will be considered if a score greater than or equal to -1.64 in one or more of the four tests is present, resulting in a dichotomous variable for each participant (decline vs no decline/improvement). For the primary cognitive outcome at 4-months post-CABG, cognitive decline (decline vs no-decline/improved) will be analysed by logistic regression with group membership (control v intervention) as the predictor variable, and covariates of age and gender.

For the secondary outcomes of all other follow-up sessions (discharge, 6-month and 1-year), cognitive decline at each time-point (always compared to pre-CABG cognition) will be used in separate logistic regressions, with group membership (control v intervention) as the predictor variable, and covariates of age and gender.

Exploratory delirium analyses will be conducted to investigate whether cognitive training affects delirium characteristics (as opposed to presence).
Delirium outcomes of severity, duration of episode and motor subtype; will be analysed with the same predictors described in previous analyses. Delirium severity (MDAS score) and days spent in a delirium episode will be investigated using linear regression and delirium motor subtype (hypoactive/hyperactive/mixed) will be investigated using multi-nominal logistic regression.

Exploratory cognitive decline analyses will be run to identify significant predictors of response to cognitive training. A series of univariate linear regressions will be conducted with the outcome being cognition change (RCI scores, as a continuous variable, calculated utilising CANTAB data for each participant at each time-point), and predictor variables will include baseline dementia risk, APOE genotype, depression, pain, delirium, gender, age, cardiovascular risk (cholesterol, glucose, blood pressure), medical history, quality of life and disability, BMI, waist-hip ratio, waist circumference, medications, education, baseline cognition (ACE-III score) and peri-operative factors (anaesthetics, time on bypass, time aorta clamped, number of bypasses, surgical complications). These analyses will be conducted on data obtained at discharge, 4- month, 6-month and 1-year follow-ups separately.

Recruitment
Recruitment status
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)
SA
Recruitment hospital [1] 10876 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 22621 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299418 0
Government body
Name [1] 299418 0
National Health and Medical Research Council
Address [1] 299418 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 299418 0
Australia
Funding source category [2] 299432 0
Charities/Societies/Foundations
Name [2] 299432 0
Heart Foundation
Address [2] 299432 0
155-159 Hutt Street
Adelaide SA 5000
Country [2] 299432 0
Australia
Primary sponsor type
University
Name
The University of South Australia
Address
University of South Australia
GPO Box 2471
Adelaide, South Australia 5001
Australia
Country
Australia
Secondary sponsor category [1] 298721 0
None
Name [1] 298721 0
Address [1] 298721 0
Country [1] 298721 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300318 0
CALHN Human Research Ethics Committee
Ethics committee address [1] 300318 0
Central Adelaide Local Health Network
CALHN Human Research Ethics Committee
Level 3, Roma Mitchell House
136 North Terrace
Adelaide, South Australia, 5000
Ethics committee country [1] 300318 0
Australia
Date submitted for ethics approval [1] 300318 0
16/11/2017
Approval date [1] 300318 0
14/12/2017
Ethics approval number [1] 300318 0
R20171020
Ethics committee name [2] 300331 0
University of South Australia Human Research Ethics Committee
Ethics committee address [2] 300331 0
University of South Australia
GPO Box 2471
Adelaide, South Australia 5001
Australia
Ethics committee country [2] 300331 0
Australia
Date submitted for ethics approval [2] 300331 0
14/12/2017
Approval date [2] 300331 0
20/12/2017
Ethics approval number [2] 300331 0
0000034053

Summary
Brief summary
Older adults are increasingly having operations on their heart, which improves heart function however often leads to problems with learning and memory (cognitive impairment). These adults are already at high risk of dementia due to poor heart health, therefore this cognitive impairment after surgery puts them at even greater risk of late-life dementia.

This project aims to decrease future dementia risk following heart surgery, in 120 patients 65 years and older, using cognitive training interventions. Learning and memory will be measured at the beginning of the study, so any changes can be assessed following surgery. The cognitive interventions will take place both before and after surgery in half of the patients. Cognitive impairment (such as delirium) will be monitored in hospital and learning and memory will be tested 4 and 6 and 12 months, and 1 and 3 years post-surgery. It is expected that patients who undertake cognitive training will demonstrate better learning and memory after surgery compared to patients who did not.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83278 0
Miss Danielle Greaves
Address 83278 0
The University of South Australia
School of Psychology, Social Work and Social Policy
GPO Box 2471, Adelaide, South Australia 5001
Country 83278 0
Australia
Phone 83278 0
+61 08 83024909
Fax 83278 0
Email 83278 0
danielle.greaves@mymail.unisa.edu.au
Contact person for public queries
Name 83279 0
Miss Danielle Greaves
Address 83279 0
The University of South Australia
School of Psychology, Social Work and Social Policy
GPO Box 2471, Adelaide, South Australia 5001
Country 83279 0
Australia
Phone 83279 0
+61 08 83024909
Fax 83279 0
Email 83279 0
danielle.greaves@mymail.unisa.edu.au
Contact person for scientific queries
Name 83280 0
Dr Hannah Keage
Address 83280 0
The University of South Australia
School of Psychology, Social Work and Social Policy
GPO Box 2471, Adelaide, South Australia 5001
Country 83280 0
Australia
Phone 83280 0
+61 08 83024340
Fax 83280 0
Email 83280 0
hannah.keage@unisa.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
Not included in ethics approval
What supporting documents are/will be available?
No other documents available
Summary results
No Results