Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000458831
Ethics application status
Approved
Date submitted
21/01/2021
Date registered
20/04/2021
Date last updated
6/10/2022
Date data sharing statement initially provided
20/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the impact of an online person-centred, multi-domain intervention program (BetterBrains) on cognitive decline.
Scientific title
A prospective, blinded endpoint, randomised controlled trial to determine the effect of an online person-centred, multi-domain, intervention program (BetterBrains) compared to general health education on cognitive decline in middle-aged community-dwelling adults with a family history of dementia.
Secondary ID [1] 301140 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Family history of dementia 317253 0
Dementia 317254 0
Alzheimer's disease 317255 0
Condition category
Condition code
Neurological 315388 315388 0 0
Dementias
Neurological 315389 315389 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The BetterBrains intervention will be delivered remotely by clinicians (i.e., registered psychologists, physiotherapists, social workers or occupational therapists; henceforth referred to as BetterBrains Coaches) trained in motivational interviewing and behaviour change strategies.

The BetterBrains intervention incorporates: (1) online risk factor screening; (2) telephone-based goal setting, coaching, and follow-up support, health care provider communication and community linkage for management of identified risk factors; and (3) provision of health education regarding dementia risk reduction; and (4) smartphone-app support to assist participants in undertaking their recommended intervention. The risk management pathway and person-centered approach of the BetterBrains intervention, means that the content, duration and frequency of the intervention provided to each participant will be unique. Participants will receive a minimum of 6 scheduled calls from their coach (3 calls over 6 weeks after baseline and 3 calls over 6 weeks at 6 months). The risk factor assessment is expected to take 40 minutes to complete. The intervention program will be implemented over 12 months with participants followed up for a further 12 months (24 months total).
A detailed program evaluation will be conducted concurrently to the RCT to assess intervention adherence and fidelity.

Below we outline each of the components and how this will be assessed for adherence/intervention fidelity.

(1) Online risk factor screening
Study participants will visit the BetterBrains study website and complete a risk factor screening assessment. The risk factor assessment comprises of 10 validated questionnaires, as well as review of participant demographic and medical/health histories, which map onto 4 risk domains each of which have a robust evidence base for dementia risk reduction: sleep (Epworth Sleepiness Scale (ESS); Insomnia Sleep Index (ISI); Pittsburgh Sleep Quality Index (PSQI)), cardiovascular health (including physical inactivity) (International Physical Activity Questionnaire (IPAQ); Medical/health history (including smoking and alcohol intake), social/cognitive engagement (Relationships Questionnaire; Educational and Occupational History) and mental health (Depression, Anxiety and Stress Scale (DASS) (21-item); Centre for Epidemiological Studies (Depression Scale), Hospital Anxiety and Depression Scale (HADS)).
Evaluation: Number of registrations and completed risk factor screening assessments.

(2) Goal setting, coaching, and follow-up telephone support for management of identified risk factors
Over a 12-month time period commencing after completion of the participant’s risk factor and baseline assessment, BetterBrains coaches will provide education and coaching to participants in the intervention group via telephone calls. Participants will receive a minimum of 6 scheduled calls from their coach. We expect that the average duration of the initial BetterBrains consultation call will be approximately 30 minutes, with all other BetterBrains coaching calls thereafter lasting approximately 15-20 minutes (on average). Coaching in these telephone calls will focus on person-centred care to optimise participant engagement.
Motivational interviewing will be used to support the participant to understand the findings of their risk assessment and to facilitate guided goal-setting based on the participant’s identified risk factors. Anticipated barriers to engagement (e.g., work and/or family commitments) will also be identified, and coaches will assist participants to find solutions to these perceived barriers. Further, coaches will also assist participants by recommending action strategies to meet specified goals, and assist with finding appropriate support services and resources local to the participant’s residential area (community linkages).
Evaluation: Identification of barriers and enablers to implementation from the perspectives of the BetterBrains coaches and participants in the trial, through participant surveys, monitoring of the online discussion forums, and interviews with the BetterBrains coaches.
Analysis of participant risk factors and intervention strategies selected and completed as per BetterBrains coaches website records.
Assessment of the degree to which BetterBrains was implemented as planned (implementation fidelity and adherence) assessed via multiple data sources (e.g., intervention documentation, including number of phone calls, smartphone app engagement, recordings/monitoring of BetterBrains coach calls).

(3) Provision of health education regarding dementia risk reduction
All participants will receive written monthly updates on general news about dementia and Alzheimer’s disease, and general psychoeducational health material about dementia risk reduction, in the form of educational blog posts, termed ‘BrainBlog’ (information will be presented in a variety of medium, including written, pictorial diagrams, and/or videos). The BrainBlog will be produced by the investigator team explicitly for study purposes. It is anticipated that participants will engage with this material for approximately 15-20 minutes (on average) each month for as long as the trial is active (a minimum of 24-months). The BrainBlog will be available to all participants and will not contain any personalised recommendations or information. All participants will also be provided with additional (optional) further reading material, which we estimate participants will engage with for an added 30-40 minutes. Material will simultaneously be available on the BetterBrains website and smartphone app.
Evaluation: Engagement via web analytics with smartphone app, webpage and the BrainBlog.

(4) Smartphone app support
If participants have a smartphone, they will be encouraged to download the BetterBrains app. The BetterBrains app will be used to assist participants in the intervention group in undertaking their recommended intervention (through weekly goal check-ins), and in the assessment of engagement and barriers to engagement. Intervention participants will receive goal check-in alerts weekly from their first intervention phone call up until week 52 of the intervention. Both intervention and control group participants will also receive a general health check-in monthly, also administered through the app. Both intervention and control group participants will also be able to communicate more readily with research team members via the app (internal message system, schedule calls, see upcoming calls). As the BetterBrains app is an optional component of the intervention intended to enhance participant experience and engagement with the clinical/research team, minimum or expected participant time spent using the app has not been specified nor estimated and will be entirely up to the discretion of the participant.
Evaluation: Useability, from the perspectives of the BetterBrains coaches and participants will be explored via participant surveys, monitoring of the online discussion forums, and interviews with the BetterBrains coaches including app and website analytics. Frameworks used to evaluate program acceptability include: Acceptability of Intervention Measure, Intervention Appropriateness Measure and Feasibility of Intervention Measure, as well as the Unified Theory of Acceptance and Use of Technology 2.
Intervention code [1] 317448 0
Prevention
Intervention code [2] 317449 0
Lifestyle
Intervention code [3] 320048 0
Treatment: Devices
Comparator / control treatment
All study participants will undergo a risk assessment. Control group participants will not receive personalized intervention recommendations. After completing their risk assessment at baseline, they will only receive mention of the number and nature of risk factors for dementia that apply to them, based on their responses. All participants will receive monthly updates on general news about dementia and Alzheimer’s disease, and general psychoeducational health material about dementia risk reduction, in the form of educational blog posts, termed ‘BrainBlog’. The BrainBlog will be produced by the investigator team explicitly for study purposes. Material will simultaneously be available on the BetterBrains website and smartphone app.
Control group
Active

Outcomes
Primary outcome [1] 323636 0
The primary composite outcome is favourable cognitive performance at 24-months defined as absence of decline from baseline (decline of less than 0.5SD) on one or more of the following cognitive tests: (a) Cogstate Detection test, (b) Cogstate One Card Learning test, (c) Cogstate One Back test, and (d) total score on the Cognitive Function Index.
Timepoint [1] 323636 0
Baseline and 24-months after baseline assessment
Secondary outcome [1] 382446 0
Change in cognitive function as assessed by the Cogstate Brief Battery.
Timepoint [1] 382446 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [2] 382447 0
Change in attention/processing speed as assessed by the Cogstate IDSST.
Timepoint [2] 382447 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [3] 382448 0
Change in learning ability as assessed by the ORCA battery.
Timepoint [3] 382448 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [4] 393028 0
Change in subjective ratings of quality of life as assessed by the RAND.
Timepoint [4] 393028 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [5] 393029 0
Change in dementia risk as assessed by the ANU-ADRI dementia risk score.
Timepoint [5] 393029 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [6] 393030 0
Change in dementia risk as assessed by the CAIDE dementia risk score.
Timepoint [6] 393030 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [7] 393031 0
Change in health literacy as assessed by the HLQ.
Timepoint [7] 393031 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [8] 393032 0
Change in motivation to change health behaviour as assessed by the Motivation to Change Health Behaviour for Dementia Risk Reduction questionnaire.
Timepoint [8] 393032 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [9] 393033 0
Change in work productivity as assessed by the VOLP questionnaire.
Timepoint [9] 393033 0
Baseline, 12- and 24-months after intervention commencement
Secondary outcome [10] 393034 0
Change in perceived risk of dementia as assessed by the Cognitive Beliefs and Perceived Risk of AD questionnaire.
Timepoint [10] 393034 0
Baseline, 12- and 24-months after intervention commencement

Eligibility
Key inclusion criteria
Community-dwelling persons, aged 40 to 70 years, fluent in the English language and who have: a first- or second-degree family history of Alzheimer's disease or dementia, resided in Australia for at least 2 years, access to a laptop or desktop computer, are willing to provide informed consent and a saliva sample for genotyping, and have at least one modifiable risk factor for dementia as identified during the online screening process, will be recruited.
Minimum age
40 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for both the control and intervention group are: a diagnosis of Alzheimer’s disease, Parkinson’s disease, Dementia with Lewy Bodies or other known diagnosis of dementia; use of TGA approved medication for the treatment of Alzheimer’s disease (e.g., donepezil, galantamine, rivastigmine, or other newly approved medication); use of any TGA approved medications for the treatment of Parkinson’s disease (e.g., sinemet, amantadine, bromocriptine, pergolide, selegiline, or other newly approved medication); history of severe traumatic brain injury or other significant neurological disease or insult (e.g., Multiple Sclerosis, Stroke); diagnosis of a major psychiatric condition (e.g., schizophrenia, uncontrolled major depressive disorder); history of alcohol or substance abuse or dependence within the past 2 years; regular (daily) use of narcotics or antipsychotic medication; history of myocardial infarction in the past year or unstable severe cardiovascular disease including angina with congestive heart failure symptoms at rest; diagnosis of epilepsy; respond “no, and I have no intention to make changes” in response to the question “have you made any changes to your lifestyle during the past year to actively reduce your risk of dementia (e.g., increasing physical activity, engaging in cognitively stimulating activities, lowering stress)?”

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 concealment: central randomisation by computer

Upon the completion of all baseline assessments, participants will be randomly assigned into the intervention (BetterBrains) or control groups in a 1:1 ratio based on the following stratification variables: (a) age (less than 55 years vs. greater than or equal to 55 years), and (b) rurality (i.e., urban vs. rural/regional based on classifications from the Australian Bureau of Statistics). Computer-generated allocation as a part of electronic Case Report Form (eCRF) will be conducted using permuted blocks of variable sizes (not disclosed in the protocol due to its public availability) after the baseline assessment. Participants will be notified of group allocation automatically via the study website.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned into the intervention (BetterBrains) or control groups in a 1:1 ratio based on the following stratification variables:
(a) age (less than 55 years vs. greater than or equal to 55 years),
(b) rurality (i.e., distance from a major urban centre)

Age and rurality were selected as stratification variables as they were considered to have a substantial impact on the primary outcome and community/health resources available to participants in the intervention group.
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
Efficacy
Statistical methods / analysis
Outcome analyses will be conducted following intention-to-treat principles. All outcomes and analyses are prospectively categorized as primary, secondary, or exploratory. Differences in all endpoints between the two study groups will be tested independently at the two-tailed 0.05 level of significance. All estimates of treatment effects will be presented with 95% confidence intervals (CIs). No formal adjustments will be undertaken to constrain the overall Type I error associated with the secondary, tertiary and exploratory analyses. Their purpose is to supplement evidence from the primary analysis to more fully characterise the treatment effect. Results from the secondary, tertiary and exploratory analyses will be interpreted in this context. Descriptive statistics will be generated for each of the measures used in study.

The primary outcome will be analysed using an adjusted logistic regression model with the achievement of a favourable cognitive outcome at 24-months (yes/no) as the dependent variable and the treatment group as the independent variable.

Secondary, tertiary and exploratory endpoints will be analysed using appropriate regression models. Exploratory longitudinal analyses will be conducted using linear mixed models (LMM) with random slopes and random intercepts to determine any between-group differences in rates of change in objective and subjective cognitive function, dementia risk, quality of life (RAND), health literacy (HLQ), motivation to change behaviour for dementia risk reduction (Motivation to Change Health Behaviour for Dementia Risk Reduction questionnaire), work productivity (VOLP), and perceived risk of dementia (Cognitive Beliefs and Perceived Risk of AD questionnaire). We will also explore the moderating effects of APOE e4, the nature and number of risk factors, and participants’ readiness to change on cognitive outcomes. The details of the statistical analysis will be summarized in a separate Statistical Analysis Plan prior to the lock of the trial data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/04/2021
Actual
19/07/2021
Date of last participant enrolment
Anticipated
21/04/2023
Actual
Date of last data collection
Anticipated
2/05/2025
Actual
Sample size
Target
1510
Accrual to date
1426
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 305583 0
Government body
Name [1] 305583 0
National Health and Medical Research Council
Country [1] 305583 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University
18 Innovation Walk, Clayton VIC 3168, Australia
Country
Australia
Secondary sponsor category [1] 308118 0
None
Name [1] 308118 0
Address [1] 308118 0
Country [1] 308118 0
Other collaborator category [1] 281337 0
University
Name [1] 281337 0
University of Melbourne
Address [1] 281337 0
Level 2,
333 Exhibition St,
Melbourne VIC 3004
Country [1] 281337 0
Australia
Other collaborator category [2] 281338 0
Commercial sector/Industry
Name [2] 281338 0
Cogstate Ltd
Address [2] 281338 0
Level 2,
255 Bourke Street,
Melbourne, VIC 3000
Country [2] 281338 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305883 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 305883 0
Ethics committee country [1] 305883 0
Australia
Date submitted for ethics approval [1] 305883 0
30/05/2020
Approval date [1] 305883 0
10/08/2020
Ethics approval number [1] 305883 0
MUHREC 2020-25221-47721

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

Contacts
Principal investigator
Name 101926 0
A/Prof Yen Ying Lim
Address 101926 0
Turner Institute for Brain and Mental Health
School of Psychological Sciences
Monash University
Room 613, 18 Innovation Walk
Clayton VIC 3800
Country 101926 0
Australia
Phone 101926 0
+61 433873222
Fax 101926 0
Email 101926 0
[email protected]
Contact person for public queries
Name 101927 0
Yen Ying Lim
Address 101927 0
Turner Institute for Brain and Mental Health
School of Psychological Sciences
Monash University
Room 613, 18 Innovation Walk
Clayton VIC 3800
Country 101927 0
Australia
Phone 101927 0
+61 433873222
Fax 101927 0
Email 101927 0
[email protected]
Contact person for scientific queries
Name 101928 0
Yen Ying Lim
Address 101928 0
Turner Institute for Brain and Mental Health
School of Psychological Sciences
Monash University
Room 613, 18 Innovation Walk
Clayton VIC 3800
Country 101928 0
Australia
Phone 101928 0
+61 433873222
Fax 101928 0
Email 101928 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?
Individual participant data will not be made publicly available. Access to de-identified data (individual participant data of published results only) can be requested from the investigator team, and approval may depend on the scientific rationale and data security and handling arrangements proposed. Any approvals will require the interested party to sign a Data Use Agreement.
When will data be available (start and end dates)?
Data will be available 3 years after the end of the trial. This is to allow the investigator team opportunity to publish key outcomes of the trial.
Available to whom?
Academic researchers
Available for what types of analyses?
Exploratory analyses
How or where can data be obtained?
Formal request to the BetterBrains Steering Committee ([email protected]), which outlines a brief proposed analysis plan, variables requested and provisions for data storage and security.


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
SourceTitleYear of PublicationDOI
EmbaseAn Online, Person-Centered, Risk Factor Management Program to Prevent Cognitive Decline: Protocol for A Prospective Behavior-Modification Blinded Endpoint Randomized Controlled Trial.2021https://dx.doi.org/10.3233/JAD-210589
EmbaseProtocol for a Mixed-Methods Process Evaluation of BetterBrains: A Person-Centered Online Intervention to Delay Cognitive Decline in Adults at Risk of Dementia.2022https://dx.doi.org/10.3233/JAD-220341
N.B. These documents automatically identified may not have been verified by the study sponsor.