Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000281594p
Ethics application status
Submitted, not yet approved
Date submitted
16/01/2024
Date registered
20/03/2024
Date last updated
20/03/2024
Date data sharing statement initially provided
20/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Brain enhancement study (BES): A multi-modal lifestyle-based intervention for individuals with amnestic mild cognitive impairment
Scientific title
Brain enhancement study (BES): Can optimising biochemical parameters (targets) via participation in a multi-modal lifestyle-based intervention improve cognition in amnestic mild cognitive impairment (MCI)?
Secondary ID [1] 311337 0
NIL known
Universal Trial Number (UTN)
Trial acronym
BES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive impairment 332592 0
Condition category
Condition code
Neurological 329286 329286 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
METHODS - THE PERSONALISED INTERVENTION (how ‘Targets’ will be met)
In all face-to-face sessions, at least one Research Team member with CPR/First-aid certification will be present.

The Intervention is designed to educate participants and facilitate behavioural change to promote progression towards Biochemical & Physiological Targets. The ultimate objective of the Intervention is to foster behaviours that:
a. Do not stimulate neurodegenerative, inflammatory, or oxidative processes, or redox imbalance,
b. Stimulate biochemical pathways known to reduce inflammatory or oxidative processes, promote repair, neurogenesis and general brain health and
c. Stimulate positive neuroplastic change.
To help participants successful make and sustain changes in their behaviour the Intervention will a) educate participants’ and their companion about the impact of lifestyle on brain health b) demonstrate how healthy lifestyle practices can be implemented and c) assist with implementation of the healthy behaviours within the participants’ home.
To achieve these objectives the Intervention is divided into three key phases (Figure 2):
- Phase 1, Preparation
- Phase 2, Intensive Workshop and
- Phase 3, Home Implementation
Figure 2. Intervention Group Schedule


12.1 Phase 1 - Preparation
The purpose of Phase 1- Preparation, is to physiologically and psychologically acclimatise both participants and their companion to the Intervention Guidelines that will be initiated during the Phase 2 - Intensive.

To achieve this, 14 days prior to commencement of the Intensive Phase, the participant and their study companion will be asked to a) reduce their intake of meat, coffee and alcohol, b) increase their fibre intake through consumption of more fruit and vegetables and c) cease consumption of non-prescribed supplements. If not already engaging in regular physical activity, participants will be asked to commence light levels of activity as appropriate for their health (e.g. walking).
12.2 Phase 2 – Intensive Workshop
To complete the Intensive Workshop Schedule, participants and their companion will visit Avondale University, another appropriate location (e.g. office space or clinical rooms), or have research staff visit their home, for 5 ½ consecutive days.
In line with the expert approved Intervention Guidelines, through both education and demonstration, the Intensive is designed to motivate participants and their companion towards adopting healthy behaviours in four key areas:
1. Nutrition
2. Physical activity
3. Optimised biorhythms (sleep/rest/time of meals)
4. Cognitive training (Computerised Cognitive Remediation Therapy)
This is achieved through:
- Educational lectures series (5x ~1 hr lectures) (Section 12.2.1),
- Modelling of meals )
- Supplement provision (Memorease + Omega 3)
- Cooking tutorials (x1) ,
- Exercise classes (x5) ,
- Computerised cognitive remediation therapy sessions (x5) .

Please Note: During the Intensive Phase participants and their companion will be provided with the Intervention Group Participant Materials .
12.2.1 Lectures
Participants and their companions will be asked to view a series of educational lectures explaining the theoretical link between brain health and positive modifications made in the four key areas listed above. The goal of the lecture series is to empower the participant/companion through knowledge, enhancing their ability to make healthy lifestyle choices and mobilise the necessary resources to do so. The viewing of nine, approximately one-hour lectures will commence on the first day of the Intensive period and run into Phase 3 – Home Implementation (Part A).

The lecture series will cover the following topics:
1. Welcome/Introduction, Our Amazing Brain, MCI, Study Overview – Intensive day 1
2. CCRT; Your Brains Gym – Intensive day 2
3. Nutrition Part 1 – Intensive day 3
4. Nutrition Part 2 – Intensive day 4
5. Supplements: What is there Place? – Intensive day 5
6. What’s Next? – Intensive day 5.5
7. The Importance of Keeping Active – Home Implementation, week 5
8. The Importance of a Good Night’s Rest – Home Implementation, week 7
9. The Importance of Maintaining Good Mental Health – Home Implementation, week 9
12.2.2 Modelling of Meals
In line with the Intervention Guidelines. an evidence based, dietician approved, brain healthy diet, will be modelled through the provision of ALL meals to both participants and their companions during the Intensive Phase.
Meals will be supplied by an external caterer who's business complies with all relevant NSW food industry legislations as outlined by the NSW Food Authority. Allergies will be check for and accommodated.
12.2.3 Supplement Provision
Participants will be asked to consume 17 g per day of a novel supplement, Memorease, and two capsules per day of Blackmores Omega Triple, Super Strength Fish Oil.
The Memorease choc supplement (developed for this study) is comprised of only Food Standards Australia and New Zealand (FSANZ), or Therapeutic Goods Australia (TGA) permissible ingredients, in permitted concentrations. Supplementation will commence during the Intensive and continue for the remainder of the study. Participants will be asked to consume two 8.5 g serves of Memorease per day after meals. Please refer to the Investigational Brochure for supplement details as well as Section 14 (Risks, Discomfort & Inconvenience), Section 16 (Adverse Event & Safety Monitoring), and Section 21 (Premature Closure of Study) of this document.
Consuming 2 capsules of Blackmores Omega Triple, Super Strength Fish Oil is the equivalent of 1080 mg Eicosapentaenoic acid (EPA) and, 720 mg Docosahexaenoic acid (DHA).
12.2.4 Cooking tutorials
To facilitate the voluntary adoption of healthy dietary practices, participants and their companion will actively participate in one Cooking Tutorial during the Intensive. This will be supplemented with an additional three Cooking Tutorials during Phase 3, Home Implementation.
In these tutorials participants and their companion will learn how to prepare simple, whole food, plant-based meals from easily obtainable ingredients. One breakfast, main meal, light meal and dessert, that meet the Nutritional Guidelines, will be demonstrated by the Intervention Facilitator also termed Study Coach in participant/companion documentation).
12.2.5 Exercise Class
During the Intensive Phase participants will take part in five, one-hour group physical activity sessions. These sessions will be run by a First-Aid/CPR qualified, personal trainer (PT) with the assistance of the Dementia Care Physiotherapist and Intervention Facilitator (if necessary). Alternative exercises will be recommended as required to accommodate each participant’s individual physical capability.
During the Intensive Phase, physical activity sessions will be held on the grounds of Avondale University, either in the gym or at another suitable venue. Alternatively, sessions may be held at a commercial gym or park as appropriate.
12.2.6 Computerised Cognitive Remediation Therapy (CCRT)
During the Intensive, participants will begin a 24 week course of computer based Cognitive Remediation Therapy (CCRT) (i.e. brain training) using the BrainHQ platform developed by Posit Science. Utilising this platform the participant will work through a series of exercises designed to improve overall brain health and recover behavioural competencies. This will take about 60 hours to complete, played out in daily 30-minute sessions, 5 days per week for 24 weeks.
The CCRT course will be initiated during the Intensive Phase under the guidance of the Associate Investigator who has received training in CCRT facilitation. Participants will continue their CCRT through Phase 3: Home Implementation. For further information about the exercises included and CCRT implementation.
12.3 Phase 3 – Home Implementation - Facilitated behaviour change
12.3.1 Home Implementation Part (A) (4 weeks)
During Home Implementation Part (A), the Intervention Facilitator will visit each participant and their companions 1-3 times per week. The number of weekly visits will be stipulated by the participant/companion and vary depending on individual needs.

During this time the Intervention Facilitator will help participants and their companions implement within the home, ALL the changes in behaviour initiated during Phase 2: Intensive. This will be in accord with the Intervention Guidelines and any personalised recommendations made within.
In partnership with the participant/companion, the Intervention Facilitator may assist in;
- Nutrition; removal/replacement of unhealthy food, locating healthy food items in store, assistance with food label reading, demonstrations of cooking techniques, adaption of recipes to suit personal tastes and study Nutritional Guidelines,
- Physical Activity; answer basic questions regarding personalised Exercise Plan,
- CCRT training; answer technical questions.
The Intervention Facilitator will also run three cooking tutorials as described in Section 12.2.4.

During this period the Intervention Facilitator and the Chief and/or Associate Investigator will have weekly meetings to discuss how each participant is progressing and any issues/concerns/complex questions raised. This will occur in consultation with the Clinical Supervisor or PT/Physiotherapist or Dietician as appropriate. The Intervention Facilitator or, if more appropriate, the Chief or Associate Investigator, will then relay the solution/outcome to the participant and companion.
12.3.1.1 Exercise Plan
During Home Implementation Part (A) participants will also begin their personalised Exercise Plan. The goal of the Exercise Plan is to facilitate participant’s progress towards the quantity of physical activity outlined in the Physical Activity Guidelines. The Exercise Plan will be developed by the PT, based on the participant’s performance in the Seniors Fitness Test administered at Assessment 1 and group exercise classes run during the Intensive. This will occur in consultation with the study Physiotherapist as required. The personalised Exercise Plan initiated at this time will be followed for six weeks (i.e. Home Implementation Part (A) plus 2 weeks of Home Implementation Part (B)).

Importantly it is recognised that each participant will start with different baseline levels of strength and aerobic fitness and have varying levels of physical aptitude. Thus, it is expected that the rate at which participant’s progress towards the level of physical activity outlined in the Intervention Guidelines will vary.
12.3.1.2 Group Physical Activity Sessions
With the primary purpose of increasing social connection and motivation, but also helping to facilitate safe exercise, participants will also commence weekly group physical activity sessions during this phase. These will be run for the duration of the study by the PT on the grounds of Avondale University or at another suitable community venue. Alternatively sessions may be held at a commercial gym or park as appropriate.
12.3.2 Home Implementation Part (B) (19 weeks)
During Home Implementation Part (B), in person visits by the Intervention Facilitator will be replaced by weekly phones calls and/or online meetings. (~15-30 min) The purpose of these calls/meetings is to monitor participant compliance and provide motivation and support as required.

The Intervention Facilitator and the Chief or Associate Investigator will have fortnightly meetings to discuss both how the participant is progressing and any issues/concerns/complex questions raised. This will occur in consultation with the study Clinical Supervisor or PT/Physiotherapist or Dietician as appropriate. The Intervention Facilitator or, if more appropriate, the Chief or Associate Investigator, will then relay the solution/outcome to the participant.
12.3.2.1 Exercise Plan Updates
After participants have completed their first 6 week personalised Exercise Plan, the participant and their companion, together with the PT or physiotherapist, and the Chief or Associate Investigator will discuss the positives and negatives of the completed plan as well as any gains in physical fitness or areas of physical concern. Based on this, the PT/physiotherapist will develop a second 6 week Exercise Plan for the participant to follow. A third and final Exercise Plan will then be developed as described above and followed for the remainder of Phase 3 – Home Implementation (i.e. until study completion). Importantly, if concerns are raised by the participant/companion at any stage, the Exercise Plan may be adjusted by the PT/physiotherapist through the course of the study.
12.3.2.2 Group Physical Activity Sessions
Group physical activity sessions will continue during this phase as described in Section 12.3.1.2 above.

12.4 How the Intervention is Personalised
The Chief Investigator or Chief and Associate Investigator, will thoroughly review the outcome of all participant assessments. Based on the Biochemical & Physiological Target results, and considering the auxiliary information derived from the Secondary Assessments and Markers, personalised recommendations within the Intervention Guidelines will be formulated such that the likelihood of meeting each Target is increased. This process will occur at the end of the 12 week assessment period in consultation with the study Clinical Supervisor, Dietician and PT/physiotherapist as appropriate.
The assessment results and personalised recommendations will then be used to populate the main body of an Assessment Report a copy of which will be provided to the participant’s primary healthcare physician(s).
Participants and their companion will meet with the Chief Investigator or Chief and Associate Investigator, either online or in person, to discuss each Assessment Report and any personalised recommendations made within. This may take up to 1 hour. During this time the participant and their companion will be encouraged to ask questions, either about the current Assessment Report specifically or the Intervention and their progress in general. Following this, the Intervention Facilitator will assist the participant and companion in implementing the personalised recommendations in the home.
Please note a log of participant attendance will be maintained for daily activities in the 5.5 day intensive and for the weekly exercise classes scheduled over the 24 weeks of the trial.
All unused supplements will be requested to be returned to the researchers at the end of each 2 weeks, when the new supplements will be distributed.
Intervention code [1] 327780 0
Lifestyle
Comparator / control treatment
The Control Group will receive standard care for this condition; essentially, as there is no treatment currently recommended for MCI this means the participant remains under the care of their primary healthcare team to take care of any relevant medical issues that may arise during the 6 month study period.
Control group
Active

Outcomes
Primary outcome [1] 337108 0
Any change in the composite assessment of neurocognitive functions and processes including psychomotor and motor speed, reasoning and planning abilities, memory and attention, and frontal, temporal and hippocampal dysfunctions.
Timepoint [1] 337108 0
Assessment at baseline, 12 and 24 weeks (primary end point) post intervention commencement
Primary outcome [2] 337315 0
Any change in the composite assessment of attention, orientation, memory, language, visual perceptual and visuospatial skills
Timepoint [2] 337315 0
Assessment at baseline, 12 and 24 weeks (primary end point) post intervention commencement
Secondary outcome [1] 430749 0
Every day function,
Timepoint [1] 430749 0
Assessed at baseline, 12 weeks and 24 weeks post intervention commencement.
Secondary outcome [2] 430750 0
Anxiety
Timepoint [2] 430750 0
baseline, 12 and 24 weeks post intervention commencment
Secondary outcome [3] 430751 0
Biomarkers of Brain Health: Neuronal damage, AD hallmark,-Plaque
Timepoint [3] 430751 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [4] 431416 0
Biomarkers of Brain Health: Neuronal damage, AD hallmark,Tangles
Timepoint [4] 431416 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [5] 431417 0
Biomarkers of Brain Health: Neuronal damage-Neuofilament life chain
Timepoint [5] 431417 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [6] 431895 0
Instrumental activities of daily living
Timepoint [6] 431895 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [7] 431896 0
Quality of life
Timepoint [7] 431896 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [8] 431897 0
Pain
Timepoint [8] 431897 0
baseline, 12 and 24 weeks after commencement of intervention
Secondary outcome [9] 431898 0
Physical function capacity
Timepoint [9] 431898 0
baseline and 24 weeks after commencement of intervention
Secondary outcome [10] 431899 0
Mood-depression
Timepoint [10] 431899 0
baseline, 12 and 24 weeks after commencement of intervention

Eligibility
Key inclusion criteria
a. Meets the National Institute on Aging-Alzheimer’s Association workgroups diagnostic guidelines for MCI due to Alzheimer’s disease (Albert 2011), as indicated by:
i. A score of 1.0-1.5 standard deviations below the age standardised mean for at least two memory associated measures plus one other measure which may or may not be memory related, as
ii. Independence in functional activities as indicated by a score greater than 51 on the Amsterdam Instrumental Activities of Daily Living (A-IADL-Q;,
iii. Change in cognition as reported by the participants study companion; indicated by a score equal to 3.19 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) OR a change in cognition as reported by a physician,
b. Aged between 65 years and 85 years,
c. Willing and able to undertake significant behavioural change in line with the intervention guidelines
d. Willing and able to adhere to personal recommendations, made within the Intervention Guidelines to facilitate meeting of Biochemical and Physiological Targets
e. Able to participate in the entire study (24 weeks) with a study companion that knows the participant well and has daily contact with the participant,
f. Able to participate in the 5 ½ day Intensive workshop (Intervention: Phase 2) with their study companion.
Minimum age
65 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

a. Known medical conditions:
i. Unstable angina,
ii. Postural hypotension (i.e. greater than 20 mmHg),
iii. Uncontrolled atrial or ventricular arrhythmias,
iv. Unstable heart failure,
v. Significant aortic stenosis,
vi. Unrecovered neurological disorder (e.g., stroke, traumatic brain injury etc.),
vii. Currently suffering from an acute inflammatory bowel condition (e.g., severe IBS, ulcerative colitis, Crohn’s disease or any other gastrointestinal condition likely to impede food absorption)
b. Currently prescribed Warfarin,
c. Prescribed medication known to significantly affect cognition (e.g., sedatives/hypnotics, narcotics, anticholinergics, 1st generation antihistamines),
d. Currently receiving chemo or radiotherapy for cancer,
e. Have received chemotherapy within the last 24 months,
f. Have undergone surgery with general anaesthesia within the last 6 months,
g. Indication of tobacco, alcohol, or other substance use disorder,
h. Concurrent participation in another study or health program,
i. Known allergy/intolerance to omega-3 supplements or the use of prescribed medications known to adversely interact with omega-3 supplements,
j. Known allergy/intolerance to ingredients within Memorease (refer to Investigational Brochure) or the use of prescribed medications known to adversely interact with ingredients within Memorease,
k. Likelihood of a current major depressive episode (as indicated by a score greater than 18 on the Cornell Scale for Depression in Dementia, CSDD or other psychological disorder (e.g., schizophrenia, obsessive compulsive disorder, Down syndrome),
l. Poorly controlled diabetes as indicated by a fasting blood glucose concentration equal to or greater than 7.0 mmol/L and/or HbA1c equal to or greater than 6.5% (48 mmol/mol),
m. Poorly controlled hyper/hypothyroidism as indicated by abnormal thyroid function test results,
n. Resting tachycardia greater than 100 bpm,
o. Systolic blood pressure equal to or greater than 180 and/or diastolic equal to or greater than 100 mmHg,
p. Uncontrolled sleep apnoea as indicated by categorisation as ‘high risk’ for sleep apnoea on the Berlin questionnaire).
q. Significant physical limitations or illness preventing compliance with study guidelines.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation involves contacting the allocation programmer who is at the central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A sequential covariate-adaptive randomisation procedure will be employed. This involves calculating the level of imbalance in covariates that assigning a participant to either Group (i.e., Intervention or Control) would cause, then allocates with high probability (to maintain a degree of randomness) the current participant to the Group that minimises the imbalance. Thus, differences at baseline between Groups are minimised, reducing the likelihood of Type I and II error (Sella 2021).

In this study each new incoming participant will be sequentially assigned in a 2:1 ratio, to the Group (Intervention or Control) that minimises Group differences between age, gender, cognition (ACEmobile score) and APOE e4 status. Calculations will be performed using the free Excel functions developed and published by Sella and colleagues (2021).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Not provided

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
7/10/2024
Actual
Date of last data collection
Anticipated
10/03/2025
Actual
Sample size
Target
51
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315592 0
Commercial sector/Industry
Name [1] 315592 0
Vitality Works
Country [1] 315592 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Vitality Works
Address
Suite 2, Level 11/157 Walker St, North Sydney NSW 2060
Country
Australia
Secondary sponsor category [1] 317685 0
None
Name [1] 317685 0
Address [1] 317685 0
Country [1] 317685 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314483 0
Bellberry
Ethics committee address [1] 314483 0
Ethics committee country [1] 314483 0
Australia
Date submitted for ethics approval [1] 314483 0
11/01/2024
Approval date [1] 314483 0
Ethics approval number [1] 314483 0

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

Contacts
Principal investigator
Name 131746 0
A/Prof Ross Grant
Address 131746 0
Avondale University, Centre for Lifestyle Medicine and Health, 582 Freemans Drive, Cooranbong NSW 2265
Country 131746 0
Australia
Phone 131746 0
+61 2 94809602
Fax 131746 0
Email 131746 0
[email protected]
Contact person for public queries
Name 131747 0
Jade Berg
Address 131747 0
Avondale University, 582 Freemans Drive Cooranbong NSW 2265
Country 131747 0
Australia
Phone 131747 0
+61 2 94809601
Fax 131747 0
Email 131747 0
[email protected]
Contact person for scientific queries
Name 131748 0
Ross Grant
Address 131748 0
Avondale University, Centre for Lifestyle Medicine and Health, 582 Freemans Drive, Cooranbong NSW 2265
Country 131748 0
Australia
Phone 131748 0
+61 2 94809602
Fax 131748 0
Email 131748 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.