Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001168842
Ethics application status
Approved
Date submitted
29/06/2021
Date registered
30/08/2021
Date last updated
17/04/2024
Date data sharing statement initially provided
30/08/2021
Date results information initially provided
17/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A holistic, interdisciplinary approach in primary care for assessing and reducing risk factors for dementia among middle-aged adults
Scientific title
A cluster randomised, controlled trial evaluating a novel Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia (HAPPI MIND) intervention aimed at assessing and reducing dementia risk factors as measured using the Australian National University - Alzheimer's Disease Risk Index (ANU-ADRI)
Secondary ID [1] 304420 0
None
Universal Trial Number (UTN)
Trial acronym
HAPPI MIND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia 322226 0
Condition category
Condition code
Neurological 319919 319919 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The main intervention will include;
• an individualised report (based on participants ANU-ADRI score) outlining risk factors known to be linked with increased risk of developing dementia in later-life.
• an educational booklet on dementia risk reduction prepared by Dementia Australia (available at https://www.dementia.org.au/sites/default/files/2020-07/20081_DA_HealthyBrainHealthyLife_A5_BOOKLET_FA_WEB.pdf).
• six individualised dementia risk reduction motivational interview sessions with a trained nurse. These sessions will occur face-to-face or via telephone or video telehealth. They will occur every 3 months for the first year then annually for a further 2 years. The first session will take 30-60minutes, with follow-up sessions likely being shorter (15-30minutes). The sessions will involve a review of the participant's dementia risk profile (and progress to date for follow-up sessions); identification of risk factors to target; discussion of capability, opportunity and motivation for behaviour change; and setting SMART (specific, measurable, attainable, realistic and timely) goals. Fidelity of the intervention will be measured using an intervention checklist completed by nurse at each session, and audio-recording at least one session at each time-point.
• a purpose-built HAPPI MIND smart phone app to support self-management of dementia risk factors at home and to track progress against risk reduction goals. Participant's will be encouraged to monitor their risk factors in accordance with their SMART goals - daily, weekly or less frequently as appropriate. Participants will be encouraged to use the app for the full three year trial. Engagement with the app (duration and frequency of use) will be evaluated using app analytics from CSIRO.
Intervention code [1] 320775 0
Prevention
Intervention code [2] 320776 0
Lifestyle
Intervention code [3] 320777 0
Behaviour
Comparator / control treatment
The minimal intervention will include;
• an individualised report (based on participants ANU-ADRI score) outlining risk factors known to be linked with increased risk of developing dementia in later-life.
• an educational booklet on dementia risk reduction prepared by Dementia Australia (available at https://www.dementia.org.au/sites/default/files/2020-07/20081_DA_HealthyBrainHealthyLife_A5_BOOKLET_FA_WEB.pdf).
• referral to general practitioner for discussing risk factors for dementia and dementia risk reduction at the next medical appointment
Control group
Active

Outcomes
Primary outcome [1] 327789 0
Change in Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI)
Timepoint [1] 327789 0
baseline, 12 months
Secondary outcome [1] 396602 0
Change in ANU-ADRI
Timepoint [1] 396602 0
baseline, 24 months and 36 months
Secondary outcome [2] 396603 0
Change in quality of life (EuroQol-5D)
Timepoint [2] 396603 0
Baseline, 12, 24 and 36 months
Secondary outcome [3] 396604 0
Change in Cardiovascular Risk Factors, Aging and Dementia [CAIDE] score
Timepoint [3] 396604 0
Baseline, 12, 24 and 36 months
Secondary outcome [4] 396629 0
Change in cognition (Montreal Cognitive Assessment score)
Timepoint [4] 396629 0
Baseline, 12, 24 and 36 months
Secondary outcome [5] 396630 0
Change in blood pressure - systolic and diastolic blood pressure (mmHg) measured using a sphygmomanometer
Timepoint [5] 396630 0
Baseline, 12 and 36 months
Secondary outcome [6] 400152 0
Change in lipids - HDL, LDL, non-HDL and triglycerides (mmol/L) using fasting blood sample
Timepoint [6] 400152 0
Baseline, 12 and 36 months
Secondary outcome [7] 400153 0
Change in risk/management diabetes - HbA1c for people with diabetes or Australian Type 2 Diabetes Risk Assessment Tool (AUDRISK) for people without diabetes
Timepoint [7] 400153 0
Baseline, 12 and 36 months
Secondary outcome [8] 400154 0
Change in smoking - nicotine dependence using heaviness of smoking index (HSI), smoking status (non-smoker, ex-smoker, current smoker), number of cigarettes smoked per day as assessed using study-specific questionnaire
Timepoint [8] 400154 0
Baseline, 12 and 36 months
Secondary outcome [9] 400155 0
Change in diet - Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet score
Timepoint [9] 400155 0
Baseline, 12 and 36 months
Secondary outcome [10] 400156 0
Change in alcohol intake - change in Alcohol Use Disorders Identification Test (AUDIT) score. (including change in total number of standard drinks per week, as assessed within the AUDIT score and ANU-ADRI score)
Timepoint [10] 400156 0
Baseline, 12 and 36 months
Secondary outcome [11] 400157 0
Change in depression - Center for Epidemiological Studies-Depression (CES-D-10) score
Timepoint [11] 400157 0
Baseline, 12 and 36 months
Secondary outcome [12] 400158 0
Change in physical activity - International Physical Activity Questionnaire (IPAQ) short form rating, days/minutes of exercise per week
Timepoint [12] 400158 0
Baseline, 12 and 36 months
Secondary outcome [13] 400159 0
Change in social engagement - Patient-Reported Outcomes Measurement Information System (PROMIS) Satisfaction with Participation in Discretionary Social Activities, Short Form score
Timepoint [13] 400159 0
Baseline, 12 and 36 months
Secondary outcome [14] 400160 0
Change in cognitive engagement - cognitive activities score from ANU-ADRI
Timepoint [14] 400160 0
Baseline, 12 and 36 months
Secondary outcome [15] 400163 0
Change in sleep – Morin Insomnia Severity Index (ISI)
Timepoint [15] 400163 0
Baseline, 12 and 36 months
Secondary outcome [16] 400164 0
Change in hearing – self-reported difficulty with hearing as assessed using study-specific questionnaire
Timepoint [16] 400164 0
Baseline, 12 and 36 months
Secondary outcome [17] 400165 0
Change in high risk medication usage – drug burden index (DBI) score
Timepoint [17] 400165 0
Baseline, 12 and 36 months
Secondary outcome [18] 400166 0
Change in GP/nurse knowledge of dementia risk reduction using the Risk factors for dementia: Frontline healthcare questionnaire
Timepoint [18] 400166 0
Baseline and 12
Secondary outcome [19] 400167 0
Change in mean individualized 5-year cardiovascular risk score (individual Framingham scores adjusted upwards)
Timepoint [19] 400167 0
Baseline, 12 and 36 months
Secondary outcome [20] 400168 0
Change in participant engagement in healthcare (patient activation measure [PAM])
Timepoint [20] 400168 0
Baseline, 12 and 36 months
Secondary outcome [21] 400169 0
economic evaluation of cost including both:
1. cost of HAPPI MIND model of care (including personnel, materials and supplies, training and app development implementation costs collected via audit of budget/spending using CostIT software), and
2. direct and indirect costs of implementing HAPPI MIND model of care from a societal perspective (including direct cost for lifestyle interventions and medications, indirect costs such as transportation and non-medical costs such as lost productivity - collected using a modified version of the “annotated cost questionnaire” developed by the Health economic Research Centre, Oxford university.
Timepoint [21] 400169 0
Baseline, 6 months, 12 months, 24 months and 36 months
Secondary outcome [22] 400170 0
Economic evaluation:
Incremental Cost-Effectiveness Ratio (ICER) between the HAPPI MIND model and the minimal intervention using ANU-ADRI and CAIDE as effectiveness measures
Timepoint [22] 400170 0
Baseline, 12 months and 36 months
Secondary outcome [23] 400171 0
Economic evaluation:
Incremental Cost-Utility Ratio (ICUR) between the HAPPI MIND model and the minimal intervention using change in quality adjusted life years (QALY)
Timepoint [23] 400171 0
Baseline, 12 months and 36 months

Eligibility
Key inclusion criteria
Community-dwelling adults, aged 45-65years, with two or more modifiable risk factors for dementia who have access to, and are able to use, a smartphone, and who have had at least one visit to the practice/clinic in the previous 12 months, will be eligible. One or more visits will indicate patient engagement with the practice/clinic.
Modifiable risk factors include: high blood pressure, hyperlipidaemia, type 2 diabetes, obesity, current smoking, physical inactivity, poor diet, excessive drinking of alcohol, depression, social isolation and lack of cognitive stimulation.
Minimum age
45 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are unable to provide informed consent, those unable to communicate in English, those with a terminal illness (anticipated survival <36 months) or those with other conditions preventing participation in the study as judged by the GP or their nominee will be excluded. Patients with a history of existing dementia, cognitive impairment or other significant neurologic disease (e.g. Parkinson’s disease, Huntington’s disease, multiple sclerosis, normal pressure hydrocephalus, progressive supranuclear palsy, seizure disorder, subdural hematoma, or history of significant head trauma with persistent neurologic sequelae or known structural brain abnormalities) will be excluded. Patients who are involved in other clinical trials targeting any of the modifiable risk factors for dementia listed above 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 concealment will be maintained through the use of sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The unit of randomisation will be the primary care clinics. Eligible primary care clinics that consent will be block randomised to either HAPPI MIND intervention or minimal intervention. The randomisation schedule has been carried out in Stata prior to the recruitment phase of the trial (using the ralloc command). Permuted blocks of 4 were applied. The allocation of treatment and control was done independent to this process.

Participants recruited from each clinic will receive the HAPPI MIND intervention or minimal intervention depending on the allocation of the clinic.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size: A medium effect (0.5 standard deviations [SD]) on the ANU-ADRI is 3.57 points. With 5% significance level and 80% power, adjusting for clustering by practice (intra-class correlation = 0.05 and cluster size 10), for a two group cRCT, the sample size required at the end of the trial is approximately 100 per arm. To allow for 20% attrition of clinics, a minimum of 26 primary care practices/GP clinics will be recruited and a minimum of 13 each randomized to intervention and control. To allow for 30% attrition of participants, recruitment will continue until 390 (195 in each arm) participants have entered the trial, i.e. on average 15 participants from each clinic.

Data will be stored in a suitable database (e.g. REDCap™) and exported for analysis in Statistical Package for Social Sciences (SPSS) (version 27.0; IBM, Armonk, NY) and Stata (ver 16, StataCorp, College Station, TX).

The mean change in ANU-ADRI scores over 12 months and 36 months in each treatment group will be estimated. Difference between groups and 95% confidence interval will be determined. Multiple linear regression analyses will be used to compare continuous outcomes between the two groups. Binary outcomes will be analysed using multiple logistic regression. All regression analyses will be adjusted for clustering, prognostic variables and potential confounders (e.g., socio-demographics, comorbidities). All primary analyses will be conducted using the intention to treat (ITT) principle. Per protocol analysis (PPA) will also be undertaken to provide a measure of reliability of the primary analysis.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/09/2021
Actual
27/09/2021
Date of last participant enrolment
Anticipated
30/04/2023
Actual
3/03/2023
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
390
Accrual to date
Final
403
Recruitment in Australia
Recruitment state(s)
NSW,VIC

Funding & Sponsors
Funding source category [1] 308785 0
Government body
Name [1] 308785 0
NHMRC Boosting Dementia Research Grants Scheme – Priority Round Five: Implementing Dementia Risk Reduction and Prevention Research (APP1171851).
Country [1] 308785 0
Australia
Funding source category [2] 308786 0
Government body
Name [2] 308786 0
NHMRC
Country [2] 308786 0
Australia
Primary sponsor type
University
Name
Monash University
Address
381 Royal Parade, Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 309695 0
University
Name [1] 309695 0
University of Newcastle
Address [1] 309695 0
University Dr, Callaghan NSW 2308
Country [1] 309695 0
Australia
Secondary sponsor category [2] 309699 0
University
Name [2] 309699 0
University of NSW
Address [2] 309699 0
Sydney NSW 2052
Country [2] 309699 0
Australia
Secondary sponsor category [3] 309700 0
University
Name [3] 309700 0
University of Melbourne
Address [3] 309700 0
Parkville VIC 3010
Country [3] 309700 0
Australia
Secondary sponsor category [4] 309701 0
University
Name [4] 309701 0
Deakin University
Address [4] 309701 0
Burwood VIC 3125
Country [4] 309701 0
Australia
Secondary sponsor category [5] 309702 0
Other Collaborative groups
Name [5] 309702 0
CSIRO Health and Biosecurity
Address [5] 309702 0
Butterfield St & Bowen Bridge Rd, Herston QLD 4029
Country [5] 309702 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308698 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 308698 0
26 Sports Walk, Clayton Campus, Research Office, Monash University VIC 3800
Ethics committee country [1] 308698 0
Australia
Date submitted for ethics approval [1] 308698 0
Approval date [1] 308698 0
27/05/2021
Ethics approval number [1] 308698 0
28273

Summary
Brief summary
While there is currently no cure for dementia, there is evidence that some health conditions and lifestyles may increase the risk of developing dementia. Some of these risk factors for dementia can exist in mid-life, well before a person may start to show signs or symptoms of dementia.

HAPPI MIND is a multi-domain intervention that brings together the expertise of different health professional groups to help reduce dementia risk factors and subsequent development of dementia in at-risk middle-aged adults. This primary care based model involves dementia risk assessment led by the practice nurse and GP, motivational interviewing to drive behavioural change, multidisciplinary management of dementia risk factors and a smart-phone app supported self-management of dementia risk factors.

The study aims to evaluate the effectiveness and cost-effectiveness of the HAPPI MIND program for assessing dementia risk and reducing dementia risk factors in middle-aged adults in the primary care setting.

It is hypothesised that primary care-based dementia risk assessment will lead to increased awareness and detection of dementia risk factors, and the tailored interdisciplinary GP/nurse-coordinated health promotion program (HAPPI MIND) will lead to reduced dementia risk, compared usual care and dementia risk assessment alone (minimal intervention).
Trial website
Trial related presentations / publications
Public notes
Procedure for enrolling participants:
1. Recruitment of practices and practice staff: Eligible primary care clinics will be identified through advertisements and consultations with Primary Health Networks (PHNs) and key informants. Direct approaches to clinics (e.g. telephone contact, direct emails with study information, brief presentations at GP continuing professional development events, presentations at practice clinical meetings, door knocking) may also be employed, particularly with clinics that have participated in previous intervention studies led by the investigators.

2. Cluster randomisation: Primary care clinics will be block randomised to main (HAPPI MIND) intervention or minimal intervention. Randomisation at the practice/clinic level will avoid contamination (i.e. the same practice managing patients from both control and intervention groups).

3. Recruitment of participants: Potentially eligible patient participants will be identified via searching primary care practice clinical databases. A trained practice nurse or authorised research assistant will search the primary care clinic database/records and identify potential candidates based on their age, medical and medication history and lifestyle (e.g. smoking status). Database searches will be conducted using general practice audit tools (e.g. Pen CS or POLAR) where possible. The nurse/authorised research assistant will then contact potentially suitable participants via telephone, SMS, email or mail (depending on preference of clinic) to confirm eligibility/interest for the recruitment interview.

The recruitment interview will occur face-to-face or via telehealth and involve confirmation of participant eligibility, provision of study information and an opportunity for potential participants to ask questions. Written informed consent will be sought by the nurse/authorised research assistant during or following this interview, once the potential participant has had sufficient time to consider their involvement.

Contacts
Principal investigator
Name 111598 0
Dr Johnson George
Address 111598 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University,
PARKVILLE, VICTORIA 3052 AUSTRALIA
Country 111598 0
Australia
Phone 111598 0
+61 399 039 178
Fax 111598 0
+613 9903 9629
Email 111598 0
[email protected]
Contact person for public queries
Name 111599 0
Dr Kali Godbee
Address 111599 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University,
PARKVILLE, VICTORIA 3052 AUSTRALIA
Country 111599 0
Australia
Phone 111599 0
+61 493 539 202
Fax 111599 0
Email 111599 0
[email protected]
Contact person for scientific queries
Name 111600 0
Dr Kali Godbee
Address 111600 0
Centre for Medicine Use and Safety
Faculty of Pharmacy and Pharmaceutical Sciences, Monash University,
PARKVILLE, VICTORIA 3052 AUSTRALIA
Country 111600 0
Australia
Phone 111600 0
+61 493 539 202
Fax 111600 0
Email 111600 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



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.