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Trial registered on ANZCTR


Registration number
ACTRN12623000407695
Ethics application status
Approved
Date submitted
14/03/2023
Date registered
21/04/2023
Date last updated
14/06/2023
Date data sharing statement initially provided
21/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
NeuroMusic: A Randomised-Controlled Trial of a Music-Based Training Program for Memory Difficulties
Scientific title
NeuroMusic: A Randomised-Controlled Trial of a Music-Based Training Program for Older Adults with Memory Difficulties
Secondary ID [1] 309195 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Neuromusic
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-associated memory impairment 329339 0
Condition category
Condition code
Neurological 326281 326281 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Music-based training programs:
The goal for both music interventions is to complete 24 hours of group training over 12 weeks. All participants will be requested to attend a 2-hour training session, once a week (minimum request of 80% participation). Lessons will be delivered by professional musicians from the Sydney Conservatorium of Music. Each session has been structured with an initial 15-minute warm-up followed by a short review of material (10-min) and the remaining portion of the class will focus on learning and practising new skills and concepts. Participants will also have a 25-minute socialisation opportunity at the end of each session. Participants are expected to achieve some repertoire each week and to work progressively on a larger repertoire. There will be no overall pressure on perfection, rather encouragement to attempt activities and participate. Instructors will focus on gradual levels of short-term achievement. Each training program will take place at the Sydney Conservatorium of Music in groups of 10 to 12 for each intervention. Progress will be recorded for each participant during each class session. Practice outside of the training session will be encouraged but will not be mandatory. If participants decide to practice at home, they will be provided with weekly guidance and given access to support resources. Participants will be asked to record their practice (e.g. time spent, type of activity) in a workbook provided by the instructor. At week 12, participants will be invited to be part of an optional group performance. The first 90 participants will be invited to receive a 60 minute 3T MRI brain scan at baseline and 12 weeks post intervenion.

a) Keyboard intervention (arm 1): Participants allocated to the keyboard intervention arm will receive keyboard lessons. Keyboard training will consist of basic piano technique and literature, music theory and dexterity exercises. At each training session, participants are expected to perform some piano repertoire and technique (finger dexterity exercises/ scales). Each lesson will include opportunities to alternate between skill development in a group setting or individual practice. To encourage practice outside of the training session, a keyboard will be provided to each participant.

b) Choral singing intervention (arm 2): The choral singing sessions will involve different strategies to learn new songs, practice listening to other participants, synchronizing personal singing parts with the rest of the choir and review of previously learned songs. The repertoire will consist of various forms of canon and rounds. The songs are selected according to different degrees of popularity and difficulty to challenge participants to adapt to their level. The choir will be accompanied by the Conductor, but there will also be options for a cappella repertoire and backing tracks if needed.

A subset of participants will be asked to attend semi-structured interviews and focus groups, via an 'opt-in' system. These will be conducted by trained members of the music team. Focus groups will consist of up to 6 participants and interviews will be one-on-one. Focus groups and interviews will be held until thematic saturation.
Intervention code [1] 325648 0
Prevention
Comparator / control treatment
Participants allocated to the active control condition will attend weekly film-viewing events for 12-weeks at the Sydney Conservatorium of Music. After each film, they will also be invited to participate in a 25-minutes afternoon tea and group discussion. The films will be approximately 45-60 minutes long and will cover a broad range of musical genres, to appeal to a broad range of tastes. Five will be documentaries, one is a feature film and one is a narrated concert. Thus, control participants will experience similar social elements as the intervention groups. After completion of the trial at 36 weeks, they will be offered the opportunity to engage with keyboard or choral singing interventions (disclosed to participants after their participation in the trial has concluded).
Control group
Active

Outcomes
Primary outcome [1] 334153 0
Efficacy of the music-based training programs as assessed by changes in verbal memory performance measured by the Rey Auditory Verbal Learning Test (RAVALT) trial 7 score (number of correct answers after 20 minutes delay).
Timepoint [1] 334153 0
Baseline, 12-weeks after randomization.
Secondary outcome [1] 419522 0
Temporal lobe cortical thickness (mm3) using Magnetic Resonance Imaging in n=90
Timepoint [1] 419522 0
Baseline and 12 weeks after implementation commencement
Secondary outcome [2] 419524 0
Prefrontal lobe cortical thickness (mm) using Magnetic Resonance Imaging in n=90.
Timepoint [2] 419524 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [3] 419525 0
Parietal lobe cortical thickness (mm) using Magnetic Resonance Imaging in n=90.
Timepoint [3] 419525 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [4] 419527 0
Default mode network (DMN) functional connectivity using resting state functional MRI in n=90.
Timepoint [4] 419527 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [5] 419529 0
Global Cognition as assessed using Preclinical Alzheimer Cognitive Composite (PACC). The PACC will be a composite score derived from: the Rey Auditory Verbal Learning Test & Wechsler Logical Memory subtest (memory); Controlled Oral Word Association Test (phonemic and semantic fluency); WAIS-IV Digit Span (working memory), the Symbol Digit modalities Test (processing speed) and the Oral Trail Making Test (executive functioning). These tests have been validated for use via videoconference.
Timepoint [5] 419529 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement.
Secondary outcome [6] 419530 0
Subjective cognitive complaints (number of points) as assessed by the British Columbia Cognitive Complaints Inventory.
Timepoint [6] 419530 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement.
Secondary outcome [7] 419532 0
Verbal learning composite (mean z-score for all tests within this composite) as determined by the Logical Memory I subtest z-score of the Wechsler Memory Scale-III (WMS-III) and the Rey Auditory Verbal Learning Test (RAVLT) trials 1-5 total z-score.
Timepoint [7] 419532 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [8] 419533 0
Verbal memory composite (mean z-score for all tests within this composite) as assessed by the Logical Memory II subtest z-score of the WMS-III and the RAVLT trial 7 z-score.
Timepoint [8] 419533 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [9] 419534 0
Processing speed composite (mean z-score for all tests within this composite) as measured by the DKEFS Colour Word Interference Test conditions 1 and 2 z-score, and the Oral Trail-Making Test (OTMT) part A z-score.
Timepoint [9] 419534 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [10] 419535 0
Executive functioning composite (mean z-score for all tests within this composite) as assessed by the DKEFS Colour Word Interference Test conditions 3 and 4 subtests z-score, the TMT part B z-score and Verbal fluency using the COWAT (letters F,A,S) z-score.
Timepoint [10] 419535 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [11] 419536 0
Depressive symptom severity (number of points) using the 15-items Geriatric Depression Scale (GDS-15).
Timepoint [11] 419536 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [12] 419537 0
Anxiety symptom severity (number of points) using the Geriatric Anxiety Scale (GAS).
Timepoint [12] 419537 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [13] 419538 0
Overall health status (number of points) as assessed by the EuroQol 5-dimension scale (EQ5D).
Timepoint [13] 419538 0
Time point: 12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [14] 419539 0
High-sensitivity C - reactive protein values (mg/L) from blood test.
Timepoint [14] 419539 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [15] 419540 0
Neurofilament light chain (Nfl) values (pg/mL) from blood test.
Timepoint [15] 419540 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [16] 419541 0
Glial fibrillary acidic protein (GFAP) values ((ng/mL) from blood test.
Timepoint [16] 419541 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [17] 419542 0
p-tau-181 values (ng/µL) from blood test. There will be a planned sub-analysis of the primary outcome in only participants found to have p-tau in their blood. There will be further exploratory analyses evaluating if changes in the blood outcomes are mediated by changes in the imaging outcomes.
Timepoint [17] 419542 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [18] 419543 0
p-tau-217 values (pg/mL) from blood test.
Timepoint [18] 419543 0
baseline and 12 weeks after intervention commencement
Secondary outcome [19] 419544 0
Amyloid-ß values from blood test.
Timepoint [19] 419544 0
baseline and 12 weeks after intervention commencement.
Secondary outcome [20] 419545 0
Self-report sleep quality (total number of points) as assessed by the Pittsburgh Sleep Quality Index (PSQI).
Timepoint [20] 419545 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [21] 419546 0
Exploratory outcome: Self-report sleep efficiency (number of points from only component 4) as assessed by the Pittsburgh Sleep Quality Index (PSQI).
Timepoint [21] 419546 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [22] 419547 0
Exploratory outcome: Daily functioning (total number of points) as determined by the Healthy Brain Ageing – Functional Assessment Questionnaire (HBA-FAQ). This will be administered to participants and one informant of each participant.
Timepoint [22] 419547 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [23] 419548 0
Exploratory outcome: Satisfaction of one’s own memory (total number of points) as assessed by the Satisfaction scale from the Multifactorial Memory Questionnaire (MMQ).
Timepoint [23] 419548 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [24] 419549 0
Exploratory outcome: Self-perception of everyday memory ability (total number of points) as assessed by the Ability scale from the Multifactorial Memory Questionnaire (MMQ).
Timepoint [24] 419549 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [25] 419550 0
Exploratory outcome: Use of practical memory strategies (total number of points) as assessed by the Strategy scale from the Multifactorial Memory Questionnaire (MMQ).
Timepoint [25] 419550 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [26] 419551 0
Exploratory outcome: Participation frequency in cognitively stimulating activities (total number of points) as determine by the Cognitive Stimulating Activity Questionnaire (CSA-Q).
Timepoint [26] 419551 0
12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [27] 419552 0
Exploratory outcome: Adherence to treatment as determined by a pre-specified value of attendance of 80% of our music-based training sessions, based on session attendance checklists.
Timepoint [27] 419552 0
12 weeks after intervention commencement
Secondary outcome [28] 419553 0
Exploratory outcome: Engagement outside practice (total hours of practice) as assessed by self-reported practice time outside of intervention attendance. This will be recorded in a practice diary. This outcome will be used as a mediator in the relationship between music intervention and MRI and cognitive outcomes.
Timepoint [28] 419553 0
12 weeks after intervention commencement. The model will also include the same information collected at baseline, and 36 weeks after intervention commencement
Secondary outcome [29] 419554 0
Exploratory outcome: Overall motivation to come to class as assessed by self-reported scores on a 10-point Likert scale ranging from 1 to 10. This outcome will be used as a mediator in the relationship between music intervention and MRI and cognitive outcomes.
Timepoint [29] 419554 0
Weeks 1-12 of the intervention.
Secondary outcome [30] 419555 0
Exploratory outcome: Participant experience of the music-based training program will be assessed by semi-structured interviews and focus groups.
Timepoint [30] 419555 0
12 weeks after intervention commencement. The model will also include the same information collected at week 4, 8, and 36 after intervention commencement.
Secondary outcome [31] 419556 0
Exploratory outcome: Actigraphy markers (e.g., sleep efficiency, nocturnal awakenings, sleep timing and total sleep time) as assessed by an actigraphy watch.
Timepoint [31] 419556 0
Time point: 12 weeks after intervention commencement. The model will also include the same test information collected at baseline, and 36 weeks after intervention commencement.
Secondary outcome [32] 419825 0
Hippocampal white matter integrity using Magnetic Resonance Imaging in n=90
Timepoint [32] 419825 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [33] 419841 0
Hippocampal volume (mm3) using Magnetic Resonance Imaging in n=90
Timepoint [33] 419841 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [34] 419842 0
Temporal lobe white matter integrity using Magnetic Resonance Imaging in n=90
Timepoint [34] 419842 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [35] 419843 0
Prefrontal lobe white matter integrity using Magnetic Resonance Imaging in n=90
Timepoint [35] 419843 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [36] 419844 0
Parietal lobe white matter integrity using Magnetic Resonance Imaging in n=90
Timepoint [36] 419844 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [37] 420199 0
Exploratory outcome: Overall motivation to complete homework by self-reported scores on a 10-point Likert scale ranging from 1 to 10. This outcome will be used as a mediator in the relationship between music intervention and MRI and cognitive outcomes.
Timepoint [37] 420199 0
Weeks 1-12 of the intervention
Secondary outcome [38] 420200 0
Exploratory outcome: Overall challenge of the class material as assessed by self-reported scores on a 10-point Likert scale ranging from 1 to 10. This outcome will be used as a mediator in the relationship between music intervention and MRI and cognitive outcomes.
Timepoint [38] 420200 0
Weeks 1-12 of the intervention
Secondary outcome [39] 420201 0
Exploratory outcome: How much practice was completed assessed by self-reported scores on a 10-point Likert scale ranging from 1 to 10. This outcome will be used as a mediator in the relationship between music intervention and MRI and cognitive outcomes.
Timepoint [39] 420201 0
Weeks 1-12 of intervention

Eligibility
Key inclusion criteria
1. Memory decline as defined by >1 standard deviation on any memory test perfomed at screening (i.e. RAVLT and/or Logical Memory)
2. Able to provide informed written consent.
3. Fluent English literacy.
4. Adults aged between 60-80 years.
5. Appropriateness to be in a group setting.
Minimum age
60 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous diagnosis of dementia or a score on the Montreal Cognitive Assessment-Blind of <18.
2. Musical instrumental playing or singing in an organised group in the last 10 years, and/or history of employment as a professional musician.
3. Attended music lessons for over 3 years
4. Problems affecting hand dexterity.
5. Impaired or not-corrected visual or auditory accuracy .
6. Previous major head injury, cerebrovascular events (stroke, TIA), or loss of consciousness equal to or greater than 30 minutes.
7. Previous or current neurological disorder diagnosis (e.g. Parkinson’s, multiple sclerosis, epilepsy).
8. Current illicit substance use or harmful alcohol intake (Alcohol Use Disorders Identification Test Consumption (AUDIT-C) score > 8).
9. Current severe major depression diagnosis as defined by a score >20 on the Patient Health Questionnaire (PHQ-9) and/or suicidal ideation (score of >1 on Q9 of the PHQ-9), or severe psychiatric or developmental disorders (e.g. Schizophrenia, bipolar disorder, autism).
10. Previously participating in any music training program or currently enrolled in another study.
11. Currently participating in or has participated in a cognitive training intervention within 4 weeks of enrolment.
12. Have been prescribed an antidepressant medication for less than four weeks or if they are experiencing side effects related to this medication.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation) which will be stratified by age.
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
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
All randomised participants will be included in the analysis of the primary endpoint to estimate treatment effect using an intention-to-treat principle.
Descriptive analyses will estimate means and proportions, confidence intervals, and measures of variability of all measures. Linear mixed models (LMMs) will be implemented to investigate changes in verbal memory performance measured by the RAVLT trial 7 between and within each group (keyboard, choral singing and control) across different time points (baseline, and 16-weeks).

The primary and secondary outcomes will be analysed via linear mixed models (LMMs) using maximum likelihood estimation. The model will include random intercepts, fixed effects of time (baseline and 16-weeks), intervention (keyboard, choral singing and control), and their interaction. Assessment of the treatment effect will be via the treatment by time interaction.

Two contrasts will be performed to assess differences in changes in the primary and secondary outcomes between:
1) the Choral Music Group and the control; and
2) the Keyboard Music Group and the control.

Appropriate effect sizes measures will be calculated (e.g., ICC for random effects, f2 for fixed effects). Multiple imputation (e.g., JM, FCS) will be implemented where necessary.

A statistical analysis plan will be prepared by the blinded study statistician and finalised prior to unblinding the data, and contain additional detail on the methods described below Data will be analysed by either the University of Sydney or the Sydney Conservatorium of Music. De-identified data may be used for future research purposes by local or international collaborators.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2023
Actual
18/05/2023
Date of last participant enrolment
Anticipated
27/01/2025
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
216
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24285 0
Brain and Mind Centre - University of Sydney - Camperdown
Recruitment postcode(s) [1] 39830 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 313390 0
Other
Name [1] 313390 0
Barbara Spencer philanthropic gift
Country [1] 313390 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Camperdown, NSW 2006
Country
Australia
Secondary sponsor category [1] 315160 0
None
Name [1] 315160 0
none
Address [1] 315160 0
N/A
Country [1] 315160 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312607 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 312607 0
Level 3, Administration Building (F23) | The University of Sydney | NSW | 2006
Ethics committee country [1] 312607 0
Australia
Date submitted for ethics approval [1] 312607 0
23/12/2022
Approval date [1] 312607 0
14/03/2023
Ethics approval number [1] 312607 0
2023/026

Summary
Brief summary
Early intervention to slow the onset of dementia is a crucial topic warranting investigation, however, to date there has been insufficient research in this field. There is evidence suggesting that older adults with memory difficulties are particularly vulnerable to developing dementia and that music training programs could have a positive effect on cognition and potentially harness the brain's ongoing ability to form new and/or reorganise existing neural pathways – 'neuroplasticity' – as well as contribute to increased wellbeing in this population. Nevertheless, there remains a paucity of research investigating the neuroprotective effects of music training in people with memory difficulties.

The unique pairing of experts from the Brain and Mind Centre and the Sydney Conservatorium of Music perfectly position us to develop, pilot and translate a ground-breaking intervention to reduce risk of cognitive decline and dementia whilst improving quality of life for older people with MCI. Thus, the main objective of this NeuroMusic study is to evaluate the efficacy of keyboard and choral singing interventions in comparison to a control condition on improving verbal memory performance. We hypothesise that in older adults with memory difficulties, our music-based training program will improve memory performance, supported by structural and functional brain changes.

This study is a 12-week, single blind, randomised-controlled trial in which 216 community dwelling older Australians (60-80 years), with memory difficulties. Participants will be randomised (1:1:1) to either the keyboard intervention, choral singing intervention or an active control condition (i.e. film-viewing sessions). Data collection points will be baseline (weeks 0-2), post-intervention (week 16) and 6 months after intervention completion (week 36).

Trial website
www.neuromusic.sydney.edu.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125266 0
Prof Sharon Naismith
Address 125266 0
Level 2 Building G, Brain & Mind Centre
100 Mallet Street, Camperdown NSW 2050
Australia
Country 125266 0
Australia
Phone 125266 0
+61 2 9351 0781
Fax 125266 0
Email 125266 0
Sharon.naismith@sydney.edu.au
Contact person for public queries
Name 125267 0
Ms Zoe Menczel Schrire
Address 125267 0
M02G, Brain and Mind Centre, The University of Sydney, NSW, 2006
Country 125267 0
Australia
Phone 125267 0
+61 2 9351 0755
Fax 125267 0
Email 125267 0
zoe.schrire@sydney.edu.au
Contact person for scientific queries
Name 125268 0
Prof Sharon Naismith
Address 125268 0
Level 2 Building G, Brain & Mind Centre
100 Mallet Street, Camperdown NSW 2050
Australia
Country 125268 0
Australia
Phone 125268 0
+61 2 9351 0781
Fax 125268 0
Email 125268 0
Sharon.naismith@sydney.edu.au

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 underlying published results only
When will data be available (start and end dates)?
Available after main trial publication with no end date determined
Available to whom?
Only researchers who provide a methodologically sound proposal
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Requirement to sign data access agreement. Using Scientific contact information in ANZCTR.
Contact Professor Naismith: sharon.naismith@sydney.edu.au


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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