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Trial registered on ANZCTR


Registration number
ACTRN12620000054910
Ethics application status
Approved
Date submitted
14/01/2020
Date registered
23/01/2020
Date last updated
23/01/2020
Date data sharing statement initially provided
23/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Lifestyle Intervention Study for Dementia Risk Reduction in Healthy Adults Aged Over 50 Years - The LEISURE study
Scientific title
A longitudinal randomised controlled trial of a multimodal lifestyle intervention for dementia risk reduction in healthy adults aged over 50ys
Secondary ID [1] 300249 0
Nil known
Universal Trial Number (UTN)
Trial acronym
LEISURE Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia 315830 0
Condition category
Condition code
Neurological 314119 314119 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lifestyle Intervention program (LIFE)

The LIFE program is a personalised multimodal lifestyle intervention designed to reduce modifiable risk factors for dementia. The LIFE program integrates exercise, diet, mindfulness, and sleep components into a comprehensive intervention specifically targeted towards metabolic, inflammatory, and neurogenic biological pathways supportive of healthy brain ageing. The LIFE program will be individually tailored to each participants’ needs across the four intervention components. Each component of the LIFE program is detailed below.

Exercise program

The exercise intervention will consist of a mixed-mode training program incorporating both supervised and unsupervised exercise. All sessions will be performed in a fitness setting with qualified personal trainers for participant supervision and instruction. Following baseline assessment and randomisation, participants will complete an introductory session with an Exercise Physiologist to assess baseline strength, educate participants on equipment use, safety, individualise the program as necessary and complete a supervised run-through of the program.

Participants will complete three, 60-min exercise training sessions per week for 12 weeks. Participants will complete one supervised session with an exercise professional per week in a small-group setting. The other two sessions per week will be completed unsupervised, with general audio-visual guidance provided in the exercise setting. Each session will include a 10-min warm-up, followed by 4-6 individually-prescribed whole-body exercises performed at a moderate intensity in a circuit-based format with minimal rest (rating of perceived exertion, Borg Scale 10-15). Resistance weight, sets, and repetitions will be aimed at improving general functional fitness (strength, balance and function) and will be set at approximately 40-60% repetition maximum, for 1-3 sets of 8-12 repetitions per exercise. Participants will then complete 10 minutes of cardiovascular exercise at a moderate to high intensity (bike, treadmill, rowing, stepping), and a 10-min cool-down. Attendance at the fitness setting where the intervention will be delivered will be monitored for participant compliance.

Intensity will be individually prescribed in the initial session and will be regularly monitored and adjusted as needed by the exercise physiologist during the supervised sessions. Modifications to exercise intensity and program difficulty will be made in a progressive manner and will take into account participant feedback, safety concerns, and recovery. The intervention will therefore be progressive, and periodised to allow for recovery, adaptation, and minimise the risk of injury.

Diet program

The intervention comprises a Modified Mediterranean diet (ModiMed), based on the Australian Dietary guidelines and the Dietary Guidelines for Adults in Greece. The ModiMed diet is rich in vegetables, fruit and whole grains with an emphasis on increased consumption of oily fish, olive oil, legumes and raw unsalted nuts. Moderate consumption of lean read meat and reduced fat dairy is included. The ModiMed diet comprises the following energy ratios: 39% total fat (e.g. 22% monounsaturated fat), 37% carbohydrates, 17% protein.

The diet program will consist of an initial one-on-one consultation (approx. 60 minutes) with an Accredited Practising Dietitian (APD), followed by six fortnightly group sessions (approx. 90 minutes), concluding with a final one-on-one post-intervention assessment. The primary focus is on increasing diet quality while reducing intake of energy dense, nutrient poor foods. Weight loss is not an aim of the intervention; rather, the intervention is designed to increase diet quality, with a focus on foods that enhance gut health.

At the first session, the dietitian will conduct a diet history (incorporating a check list of commonly-consumed foods) to assess usual dietary intake. This will be done using a seven-day food diary. Additional sessions will incorporate goal setting, label reading, motivational interviewing techniques, and mindful eating, as part of the individualised dietetic support. Participants are encouraged to set personalised goals at each session and identify barriers/motivators to change. In the group-based sessions, participants will participate in group discussions and receive dietetic and peer support focused on identifying and addressing barriers to healthy eating and increasing capacity for sustained dietary change. They will have the opportunity to ask questions of the dietitian and also to receive guidance and support regarding food shopping, as well as recipes focussed on simple, healthy, affordable, tasty meals using Mediterranean-style dietary principles. At the final session, which is once again an individual session, goals achieved are summarised, with longer term strategies for achieving sustainable change addressed. Compliance with the diet will be assessed using the Food Frequency Questionnaire (FFQ).

Mindfulness program

The mindfulness program will utilise a standardised mindfulness technique developed for use in longitudinal RCTs. The mindfulness training will begin by using a mindful breathing task and will then slowly be expanded to include all activities of daily living.

The program will consist of eight instructor-led group training sessions of approximately 90 minutes duration. Participants will attend group sessions weekly during the first four weeks of the intervention (4 sessions) and then fortnightly thereafter on weeks six, eight, ten and 12 (4 sessions). These sessions will focus upon the delivery of the mindfulness technique and instructions to participants. Participants will also have the opportunity to discuss their experience with the program and receive personalised advice regarding their mindfulness practice, as well as engage in a group practice session during which participants will receive guided instructions to advance their practice. The home practice component will begin at 20 min/day at the outset, increasing to 30 min/day after week 2 for the remainder of the program. Participants will be required to keep a home training diary to record time spent engaged in the exercises to monitor compliance with the mindfulness component of the intervention.

Sleep program

The primary focus of the sleep program will be to optimise sleep quality, quantity, and daytime functioning, as measured through both objective (sleep diary and actigraphy monitoring) and subjectively (through self-report). The sleep will consist of an initial one-on-one consultation with a sleep clinician, followed by six fortnightly group sessions, concluding with a final one-on-one session. The intervention will involve sleep hygiene education designed to improve sleep quality.

Participants will complete a baseline seven-day sleep diary and actigraphy monitoring. Following this there will be a group-based orientation session to provide background and necessary information regarding the program, including the research evidence for sleep therapy. This will provide a strong rationale and impetus to the participants in making the necessary commitment to sleep change. Participants will subsequently receive six fortnightly support sessions of approximately 60 minutes each over the course of the 12-week program. The final post-intervention assessment session will be once again an individual session. Sleep improvement will be determined by post-intervention actigraphy monitoring to assess sleep quality and length over seven days, and attendance at individual and group sessions will be recorded to assess participant engagement with the program.

Participants will be encouraged to set personalised goals at each session and identify barriers/motivators to change. In the group-based sessions, participants will participate in group discussions and receive clinician and peer support focused on identifying and addressing barriers to healthy sleep behaviours and patters and increasing capacity for sustained change. They will have the opportunity to ask questions of the clinician and also to receive guidance and support. At the final session, which is once again an individual session, goals achieved are summarised, with longer term strategies for achieving sustainable change addressed.
Intervention code [1] 316536 0
Prevention
Intervention code [2] 316537 0
Lifestyle
Intervention code [3] 316538 0
Behaviour
Comparator / control treatment
Treatment-as-usual (TAU)

The TAU program consists of the comprehensive baseline medical, mood, and neuropsychological assessments used to determine participants’ individual dementia risk profile. A detailed report outlining this dementia risk profile, together with a summary of participants’ cognitive strengths and weaknesses, will be sent to the participants’ referring GP to inform them of the outcome of the assessments. Where appropriate, this report will also include recommendations for on-going monitoring or management to ensure they are cared for under existing health care models.
Following baseline assessment and feedback reporting, participants in the TAU program will then be booked to attend 12-week follow-up assessments in the HBA clinic to determine the effectiveness of their usual care model in reducing their dementia risk profile. During the 12-week period, participants will not be provided with additional intervention material from the HBA clinic.
Control group
Active

Outcomes
Primary outcome [1] 322503 0
HBA Dementia Risk Profile Report
Timepoint [1] 322503 0
Post 12-week intervention
Secondary outcome [1] 378724 0
Change in regional brain volumes as assessed by structural MRI scan
Timepoint [1] 378724 0
Post 12-week intervention
Secondary outcome [2] 378725 0
Changed resting state functional network activation as assessed by resting state functional MRI scan
Timepoint [2] 378725 0
Post 12-week intervention
Secondary outcome [3] 378726 0
Changed white matter connectivity as assessed by Diffusion Tensor Imaging (DTI) MRI scan
Timepoint [3] 378726 0
Post 12-week intervention
Secondary outcome [4] 378727 0
Change in neurometabolites as assessed by Magnetic resonance spectroscopy (MRS)
Timepoint [4] 378727 0
Post 12-week intervention
Secondary outcome [5] 378728 0
Change in Electroencephalogram (EEG) power and connectivity as measured by 32-channel EEG system
Timepoint [5] 378728 0
Post 12-week intervention
Secondary outcome [6] 378729 0
Change in EEG Event-related Potential (ERP) as measured by 32-channel EEG system
Timepoint [6] 378729 0
Post 12-week intervention
Secondary outcome [7] 378730 0
Change in attentional performance as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB)
Timepoint [7] 378730 0
Post 12-week intervention
Secondary outcome [8] 378732 0
Change in cerebrovascular function as measured by transcranial doppler (TCD)
Timepoint [8] 378732 0
Post 12-week intervention
Secondary outcome [9] 378734 0
Change in blood biomarker profile as measured by Enzyme-linked immunosorbent assay (ELISA)
Timepoint [9] 378734 0
Post 12-week intervention
Secondary outcome [10] 378735 0
Change in insulin resistance as measured by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score
Timepoint [10] 378735 0
Post 12-week intervention
Secondary outcome [11] 378738 0
Change in global cognitive function assessed by Montreal Cognitive Assessment (MoCA).
Timepoint [11] 378738 0
Post 12-week intervention
Secondary outcome [12] 378739 0
Changed glymphatic flow as assessed by cardiac flow MRI scan
Timepoint [12] 378739 0
Post 12-week intervention
Secondary outcome [13] 378740 0
Change in working memory capacity assessed by Digit Span subtest (Wechsler Adult Intelligence Scale, IV)
Timepoint [13] 378740 0
Post 12-week intervention
Secondary outcome [14] 378741 0
Change in visual attention and task switching assessed using the Trail making test.
Timepoint [14] 378741 0
Post 12-week intervention
Secondary outcome [15] 378742 0
Change in memory assessed by WMS-IV Logical Memory I and II (Wechsler Memory Scale, IV).
Timepoint [15] 378742 0
Post 12-week intervention
Secondary outcome [16] 378743 0
Change in visuospatial memory assessed by Rey Complex Figure Test
Timepoint [16] 378743 0
Post 12-week intervention
Secondary outcome [17] 378744 0
Change in verbal fluency assessed by Controlled Oral Word Association Test
Timepoint [17] 378744 0
Post 12-week intervention
Secondary outcome [18] 378747 0
Change in auditory-verbal memory assessed by Rey Auditory Verbal Learning Test
Timepoint [18] 378747 0
Post 12-week intervention
Secondary outcome [19] 378749 0
Change in inhibitory control performance assessed by D-KEFS Colour –Word Interference Test.
Timepoint [19] 378749 0
Post 12-week intervention
Secondary outcome [20] 378750 0
Change in reaction time to ERP task target stimuli as measured in milliseconds
Timepoint [20] 378750 0
Post 12-week intervention
Secondary outcome [21] 378751 0
Improved response accuracy to ERP task target stimuli as measured by percent correct responses
Timepoint [21] 378751 0
Post 12-week intervention
Secondary outcome [22] 378752 0
Change in word retrieval assessed by Boston Naming Test.
Timepoint [22] 378752 0
Post 12-week intervention
Secondary outcome [23] 378753 0
Change in perceived cognitive difficulties assessed by British Columbia Cognitive Complaints Inventory (BC-CCI).
Timepoint [23] 378753 0
Post 12-week intervention
Secondary outcome [24] 378754 0
Change in depressive symptoms assessed by Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D).
Timepoint [24] 378754 0
Post 12-week intervention
Secondary outcome [25] 378755 0
Change in symptoms of anxiety assessed by State/Trait Anxiety Inventory.
Timepoint [25] 378755 0
Post 12-week intervention
Secondary outcome [26] 378756 0
Change in sleep duration as determined by actigraphy monitoring and 7-day sleep diary completion
Timepoint [26] 378756 0
Post 12-week intervention
Secondary outcome [27] 378757 0
Change in sleep quality as determined by actigraphy monitoring and 7-day sleep diary completion
Timepoint [27] 378757 0
Post 12-week intervention
Secondary outcome [28] 378758 0
Change in sleep onset latency defined by actigraphy and 7-day sleep diary
Timepoint [28] 378758 0
Post 12-week intervention
Secondary outcome [29] 378759 0
Change in mindfulness as measured by breath counting task
Timepoint [29] 378759 0
Post 12-week intervention
Secondary outcome [30] 378760 0
Change fitness as measured by a 6-minute walk test
Timepoint [30] 378760 0
Post 12-week intervention
Secondary outcome [31] 378761 0
Change in leg strength as measured by sit-to-stand test
Timepoint [31] 378761 0
Post 12-week intervention
Secondary outcome [32] 378762 0
Change in strength as measured by the grip strength test
Timepoint [32] 378762 0
Post 12-week intervention
Secondary outcome [33] 378763 0
Change in aspects of quality of life as measured by the Assessment of Quality of Life (AQoL)-8D
Timepoint [33] 378763 0
Post 12-week intervention
Secondary outcome [34] 378764 0
Change in health resource use as measured by the Health Resource Use Questionnaire
Timepoint [34] 378764 0
Post 12-week intervention
Secondary outcome [35] 378765 0
Change in diet quality as measured by 7-day food diary
Timepoint [35] 378765 0
Post 12-week intervention

Eligibility
Key inclusion criteria
1. Individuals aged 50-85 years with a Montreal Cognitive Assessment (MoCA) score of 26 or greater;
2. Availability to complete all testing, training, and home practice requirements;
3. Normal or corrected-to-normal visual acuity;
4. Pass MRI safety checklist.
Minimum age
50 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Prior head injury with loss of consciousness >60 minutes
2. Stroke or TIA.
3. Atherosclerotic cardiovascular disease.
4. Myocardial infarction (heart attack).
5. Pulmonary respiratory conditions (eg: COPD).
6. Metabolic disorders (diabetes type 1 +2; kidney disease; liver disease)
7. History of schizophrenia, bipolar, or non-affective psychiatric disorder (eg: ADHD, CFS, PTSD).
8. Major neurological condition (eg: Parkinson’s disease, Multiple sclerosis).
9. Epilepsy.
10. Current or past alcohol or other substance misuse.
11. Intellectual disability.
12. Acute psychosis.
13. Insufficient English language skills to complete standardised assessment.
14. Test results that indicate study participation is unsafe.
15. Participation in conflicting studies.

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)
Randomisation will be completed by a HBA team member using a GraphPad randomisation software tool, where a double random allocation to group ensures that intervention assignment is randomly conducted. Participants will receive the randomisation outcome letter in a sealed envelope following their T1 assessments.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
GraphPad randomisation software tool using double random allocation to group ensuring that intervention assignment is randomly conducted.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The study design is a parallel groups design (TAU and LIFE), however participants allocated to the TAU condition will be provided the option to enter the LIFE condition after their 12-week follow-up assessments are completed.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Correlational analysis will be performed on MRI data, EEG data, behavioural data, and psychological data to uncover associations between observed changes. Repeated measures mixed design ANOVA will be used to investigate between-within group changes.

Recruitment
Recruitment status
Not yet 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)
QLD

Funding & Sponsors
Funding source category [1] 304674 0
Charities/Societies/Foundations
Name [1] 304674 0
Wilson Foundation
Address [1] 304674 0
GPO Box 4658
Sydney NSW 2001
Country [1] 304674 0
Australia
Primary sponsor type
University
Name
University of the Sunshine Coast
Address
Sunshine Coast Mind and Neuroscience - Thompson Institute
12 Innovation Parkway,
Birtinya, 4575. QLD.
Country
Australia
Secondary sponsor category [1] 304979 0
Individual
Name [1] 304979 0
Dr Ben Isbel
Address [1] 304979 0
Sunshine Coast Mind and Neuroscience - Thompson Institute
12 Innovation Parkway,
Birtinya, 4575. QLD.
Country [1] 304979 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305095 0
University of the Sunshine Coast Human Research Ethics Committee (USC HREC)
Ethics committee address [1] 305095 0
Human Research Ethics Committee University of the Sunshine Coast Locked Bag 4 MAROOCHYDORE DC QLD 4558 AUSTRALIA
Ethics committee country [1] 305095 0
Australia
Date submitted for ethics approval [1] 305095 0
26/09/2019
Approval date [1] 305095 0
06/01/2020
Ethics approval number [1] 305095 0
A191301

Summary
Brief summary
The LEISURE Study aims to assess the efficacy of a 12-week multimodal lifestyle intervention program incorporating exercise, diet, mindfulness and sleep compared to care-as-usual to reduce dementia risk in a group of healthy older adults. Participants’ risk profile will be assessed using novel biomarkers in conjunction with comprehensive neuropsychological and neuroimaging techniques.

The rationale for the trial is founded upon a body of evidence that now suggests AD may be classified as an age-related metabolic neurodegenerative and vascular disease, wherein aberrant metabolic and inflammatory signalling leads to a cascade of neurotoxic changes that result in impaired cognitive function. Using this framework, each component of the multimodal lifestyle intervention has been chosen to target specific metabolic or vascular regulatory systems to promote neurogenesis, leading to improved cognitive function and reduced dementia risk. The LEISURE study aims to assess whether such multimodal lifestyle interventions are more efficacious than care-as-usual in reducing multiple risk factors implicated in the aetiology of dementia, particularly AD.

The LEISURE study is unique in combining leading neuroimaging techniques with novel biomarker identification to develop a new model of dementia prevention through non-pharmacological lifestyle approaches. While the field of lifestyle interventions for dementia prevention is in its infancy, the LEISURE study will provide crucial insight into the biomolecular mechanisms underpinning healthy brain ageing.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99254 0
Dr Ben Isbel
Address 99254 0
Sunshine Coast Mind and Neuroscience - Thompson Institute 12 Innovation Parkway, Birtinya, 4575. QLD.
Country 99254 0
Australia
Phone 99254 0
+61 7 5456 3935
Fax 99254 0
Email 99254 0
bisbel@usc.edu.au
Contact person for public queries
Name 99255 0
Dr Ben Isbel
Address 99255 0
Sunshine Coast Mind and Neuroscience - Thompson Institute 12 Innovation Parkway, Birtinya, 4575. QLD.
Country 99255 0
Australia
Phone 99255 0
+61 7 5456 3935
Fax 99255 0
Email 99255 0
bisbel@usc.edu.au
Contact person for scientific queries
Name 99256 0
Dr Ben Isbel
Address 99256 0
Sunshine Coast Mind and Neuroscience - Thompson Institute 12 Innovation Parkway, Birtinya, 4575. QLD.
Country 99256 0
Australia
Phone 99256 0
+61 7 5456 3935
Fax 99256 0
Email 99256 0
bisbel@usc.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
No IPD sharing has been approved under the ethics approval for this study.
What supporting documents are/will be available?
No other documents available
Summary results
No Results