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Trial registered on ANZCTR


Registration number
ACTRN12615001347550
Ethics application status
Approved
Date submitted
3/12/2015
Date registered
10/12/2015
Date last updated
9/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of computerised cognitive training on memory outcomes in older adults with documented cognitive decline.
Scientific title
A randomised controlled trial in older adults with documented cognitive decline of computerised cognitive training compared to active control training on memory outcomes.
Secondary ID [1] 287477 0
nil
Universal Trial Number (UTN)
UTN U111111758096.
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary prevention of cognitive decline 296220 0
Condition category
Condition code
Neurological 296493 296493 0 0
Dementias
Mental Health 296541 296541 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Supervised multi-domain computerised cognitive training using Captain's Log MindPower Builder. There will be small group training sessions with a maximum of 8 participants per session and two supervisors. One of the supervisors has a background in conducting clinical trials with Computerised Cognitive Training and the other supervisor will be a clinical neuropsychologist.

There will be an attendance log kept by the supervisor and there is also a computer login date and time recorded per participant.

In months 1-3, participants undergo 24 training sessions (2 sessions per week, 60 minutes per session for 12 weeks).
In months 4-18, participants will be asked to complete a 60-minute booster session every month. Participants whose within-session performance on one or more cognitive exercises falls to below 15% of their post-training maxima will be invited to attend three additional 60-minute booster sessions the following week.
Intervention code [1] 292860 0
Prevention
Intervention code [2] 292861 0
Treatment: Other
Comparator / control treatment
In months 1-3, participants undergo supervised, intensity matched, general activity didactic viewing and
listening exercises over 24 sessions (2 sessions per week, 60 minutes per session for 12 weeks).
In months 4-6, participants receive supervised multi-domain computerised cognitive training using the Captain's Log MindPower Builder over 24 training sessions (2 sessions per week, 60 minutes per session for 12 weeks).
There will be no additional intervention between months 7-18.

The didactic viewing and listening exercises are administered by the computer and can be repeated on request.
Control group
Active

Outcomes
Primary outcome [1] 300347 0
The RAVLT: Ability to learn new information, assessed by the Sum of Trials 1-5 (total learning).
Timepoint [1] 300347 0
all time points: baseline, 3 months, 6 months, 18 months
Primary outcome [2] 300348 0
The RAVLT: Trials 7 score will measure delayed recall ability in memory.
Timepoint [2] 300348 0
Baseline, 3, 6, and 18 months
Secondary outcome [1] 317554 0
1. Global cognition change: based on pre-specified summary z-score composite across 5 cognitive domains: memory (WMS-III Logical memory I and II, Rey Auditory Verbal Learning Test, and Rey Complex Figure), attention(WAIS-III Digit span), executive functions (DKEFS Stroop, DKEFS Sorting and Trials B), processing speed (Symbol Digit Modalities Test, Trailmaking A), and language (Verbal Fluency test).
Timepoint [1] 317554 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [2] 317673 0
2. Global Clinical change: clinical dementia rating scale sum-of-boxes
Timepoint [2] 317673 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [3] 319380 0
3. Functional Change: ADCS-ADL-Prevention questionnaire
Timepoint [3] 319380 0
At baseline and after 3, 6 and 18 months
Secondary outcome [4] 319382 0
4i. Change in individual cognitive domains measured in separate summary z-score composites. Memory: based on a pre-specified summary z-score composite of the following tests-WMS-III Logical memory I and II, Rey Auditory Verbal Learning Test, and Rey Complex Figure)
Timepoint [4] 319382 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [5] 319383 0
4ii. Change in individual cognitive domains measured in separate summary z-score composites. Attention/Working memory: based on a pre-specified summary z-score composite of the following tests- WAIS-III Digit Span, IVA-2
Timepoint [5] 319383 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [6] 319384 0
4iii. Change in individual cognitive domains measured in separate summary z-score composites. Processing Speed: based on a pre-specified summary z-score composite of the following tests- Symbol Digit Modalities Test, oral version, Trail Making A
Timepoint [6] 319384 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [7] 319385 0
4iv. Change in individual cognitive domains measured in separate summary z-score composites. Language:based on a pre-specified summary z-score composite of the following test- Verbal Fluency
Timepoint [7] 319385 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [8] 319386 0
4v. Change in individual cognitive domains measured in separate summary z-score composites. Executive Functions: based on a pre-specified summary z-score composite of the following tests-DKEFS Stroop, DKEFS Sorting, and Trails B
Timepoint [8] 319386 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [9] 319387 0
5. Change in Quality of life: World Health Organisation Quality of Life Scale (WHOQOL)
Timepoint [9] 319387 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [10] 319388 0
6. Change in mood and mental health symptoms: 16-item Geriatric Depression Scale (GDS)
Timepoint [10] 319388 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [11] 319389 0
7. Change in sleep-wake systems: diary and actigraphy

.
Timepoint [11] 319389 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [12] 319390 0
8. Change in Risk perception: an economic decision-making test known to be age-sensitive. (Based on significant findings from the results of previous study done by one of our investigators that measured choice consistency, rationality, and preferences for known and unknown risks)

Tymula A, Belmaker L, Ruderman L, Glimcher PW, Levy I (2013) Like Cognitive function, decision making across the life span shows profound age-related changes. PNAS 110(42): 17143-17148
Timepoint [12] 319390 0
At baseline and after 3, 6 and 18 months.
Secondary outcome [13] 319425 0
Gene-response relationships: saliva samples will be taken from all participants at baseline. A genome-wide association study will examine the relationship between genetic polymorphism and response to CCT.
Timepoint [13] 319425 0
baseline
Secondary outcome [14] 319426 0
MRI scan:
1. Structural imaging (3D whole-brain T1 high resolution 1mm isotropic, and T2 high resolution hippocampal scans),
These measures will be acquired from a subsample of 50% of participants, based on 1:1 randomisation within each group
Timepoint [14] 319426 0
At baseline and after 3 months.
Secondary outcome [15] 319427 0
MRI scan:
2. Resting-state functional MRI : To explore if cognitive phenotype and hippocampal morphometry before training onset are potential predictors of ultimate clinical response.
These measures will be acquired from a subsample of 50% of participants, based on 1:1 randomisation within each group
Timepoint [15] 319427 0
At baseline and after 3 months.
Secondary outcome [16] 319428 0
MRI scan:
3. MR spectroscopy of the hippocampus. To explore if hippocampal morphometry before training onset are potential predictors of ultimate clinical response.
These measures will be acquired from a subsample of 50% of participants, based on 1:1 randomisation within each group
Timepoint [16] 319428 0
At baseline and after 3 months.

Eligibility
Key inclusion criteria
Older adults (aged 60 years or older) with documented longitudinal cognitive decline unresponsive to intervention (not attributable by illness or new medication onset): those individuals who, over the course of at least 6-24 months and multiple neuropsychological assessments have had any memory-related test decline by at least 0.5SD of age-corrected norms despite routine clinic intervention. Memory tests administered by the clinics include: WMS-III Logical memory (I and II), the RAVLT and the Rey Complex Figure.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) history, diagnosis or treatment for dementia (of any aetiology); (2) current use of third-generation or tricyclic antidepressants; (3) history of stroke in last 12 months; (4) major neurological disorder requiring current treatment (epilepsy, Parkinson's disease); (5) major psychiatric disorder requiring current treatment (schizophrenia, bipolar disorder); (6) physical (sensory or motor) impairment that would limit training; (7) current undertaking of any other computerised cognitive training (CCT) program; (8) current alcohol dependence or abuse (defined as drinking over NHMRC guidelines); (9) definitive exclusion of possible undiagnosed major depression using the Geriatric Depression Scale (15-item score 10 or greater) or Hamilton Rating Scale for Depression (17-item score 12 or greater) i.e. if participants were found to have clinical depression scores at baseline measurement that were not previously diagnosed, these participants will be excluded.

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)
Allocation will be performed by contacting a fully-blinded, independent statistician at the NHMRC Clinical Trials Centre at USYD after completion of baseline assessments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A stratified block-based randomisation strategy to aid matching on age, sex and entry-level cognitive status (MMSE) will be conducted and managed by an independent agent.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
1:1 allocation.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Aim 1 (efficacy of high intensity centre-based CCT) will be tested using an intention-to-treat approach using recommended Linear Mixed Modelling. We will evaluate a model including main effects for Group, Time and the main interaction term of interest: Group (Arm A vs Arm B) X Time (FU1 to FU2). Covariates will only be added if baseline differences are noted between groups.

Aim 2 (efficacy of maintenance dose CCT) will be addressed using an intention-to-treat approach using Linear Measures Mixed Modelling. We will test a model including main effects for Group, Time and the main interaction term of interest: Group (Arm A vs Arm B) X TIME (FU3 to FU4). Covariates will only be added if baseline differences are noted between groups.

Aim 3 (efficacy on secondary outcomes) will be addressed as per Aims 1 and 2 for each secondary outcome separately.

Aim 4 (clinical response prediction): will be addressed by multiple regression examining relationships between baseline predictor variables (i.e., cognitive phenotype, or hippocampal measures or genotype) and cognitive change scores.

This study is powered on the basis of a relative effect size (RES) on Global Cognition of 0.44 at the end of the Phase I RCT (based on average from our Timecourse Trial results and our NHMRC SMART trial). Designate power of 0.90 controlling a at 0.05 translates to a required sample size of N=68 (calculated using G*Power 3.1 based on ANOVA repeated measures within-between interaction test, 2 groups, 2 time-points, within subject autocorrelation =0.4, equivalent effect size of [v]=0.22). A sample of N=86 (rounded up from 85) will be recruited to allow for 20% overall attrition (as per Timecourse Trial extrapolated to 15-months).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
We were unable to obtain the correct contract of service required from the intervention company required for the University of Sydney governance
Date of first participant enrolment
Anticipated
3/01/2016
Actual
Date of last participant enrolment
Anticipated
3/08/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
86
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4835 0
Prince of Wales Private Hospital - Randwick
Recruitment hospital [2] 4836 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 12342 0
2031 - Randwick
Recruitment postcode(s) [2] 12344 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 292055 0
Government body
Name [1] 292055 0
National Health and Medical Research Council of Australia
Country [1] 292055 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
University of Sydney,
Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 291014 0
None
Name [1] 291014 0
Address [1] 291014 0
Country [1] 291014 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293539 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 293539 0
Ethics committee country [1] 293539 0
Australia
Date submitted for ethics approval [1] 293539 0
Approval date [1] 293539 0
04/09/2015
Ethics approval number [1] 293539 0
2015/564
Ethics committee name [2] 293965 0
SESLHD HREC
Ethics committee address [2] 293965 0
Ethics committee country [2] 293965 0
Australia
Date submitted for ethics approval [2] 293965 0
Approval date [2] 293965 0
Ethics approval number [2] 293965 0

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

Contacts
Principal investigator
Name 60358 0
A/Prof Michael Valenzuela
Address 60358 0
Regenerative Neuroscience Group, Brain and Mind Centre
Room 408, Level 4, Bldg M02K
94 Mallett St Camperdown,
NSW, 2050 Australia
Country 60358 0
Australia
Phone 60358 0
+61 2 9114 4135
Fax 60358 0
+61 2 9351 0930
Email 60358 0
[email protected]
Contact person for public queries
Name 60359 0
Amit Lampit
Address 60359 0
Regenerative Neuroscience Group, Brain and Mind Centre
Room 408, Level 4, Bldg M02K
94 Mallett St Camperdown,
NSW, 2050 Australia
Country 60359 0
Australia
Phone 60359 0
+61 2 9351 0893
Fax 60359 0
+61 2 9351 0930
Email 60359 0
[email protected]
Contact person for scientific queries
Name 60360 0
Amit Lampit
Address 60360 0
Regenerative Neuroscience Group, Brain and Mind Centre
Room 408, Level 4, Bldg M02K
94 Mallett St Camperdown,
NSW, 2050 Australia
Country 60360 0
Australia
Phone 60360 0
+61 2 9351 0893
Fax 60360 0
+61 2 9351 0930
Email 60360 0
[email protected]

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