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Trial registered on ANZCTR


Registration number
ACTRN12619000182190
Ethics application status
Approved
Date submitted
19/10/2018
Date registered
8/02/2019
Date last updated
8/02/2019
Date data sharing statement initially provided
8/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Brain stimulation for the improvement of thinking and memory skills in Mild Cognitive Impairment
Scientific title
A longitudinal investigation of the neurophysiological changes related to cognitive performance and the effects of neuromodulation in Mild Cognitive Impairment
Secondary ID [1] 296334 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 310050 0
Memory difficulties 310051 0
Condition category
Condition code
Neurological 308803 308803 0 0
Other neurological disorders
Mental Health 308804 308804 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial alternating current stimulation (tACS) involves the application of a weak alternating electrical current to the scalp to non-invasively increase cortical excitability.
A stimulation course of active gamma-tACS at 40Hz will be applied to the left prefrontal cortex at 1mA for 20-minutes per treatment during two Acute Phases (4 weeks) of treatment. Each Acute Phase is separated by a period of 6 months. . This treatment sequence will be repeated each year for a total of three years. Participants will self-administer treatments in their own home following supervised training at the Monash Alfred Psychiatry research centre. Treatment adherence will be monitored using device analytics.
Intervention code [1] 312700 0
Treatment: Devices
Comparator / control treatment
A stimulation course of sham gamma-tACS will be applied to the left prefrontal cortex at 1mA. Sham tACS sensations are similar to active tACS but without an active current. Neuropsychosocial outcomes and cognitive performance will be compared pre- and post-tACS across the two groups (active and placebo tACS).
Control group
Placebo

Outcomes
Primary outcome [1] 307823 0
The primary outcome, cognitive performance, will be assessed using a comprehensive battery of composite neuropsychological tests. These composite outcomes include the TOPF, BVMT, RAVLT, Trail Making Test, forward and backward Digit Span, Verbal Fluency, Stroop, Rey Complex (Copy), Digit Symbol Coding, Rey Complex (delay/recall), BNT.
Timepoint [1] 307823 0
One week pre-Acute Phase, immediately post-Acute Phase, three months post-acute phase, six months post-Acute Phase, nine months post-Acute Phase and 12-months post Acute Phase (primary endpoint).
Primary outcome [2] 307824 0
TMS-EEG evoked potential amplitudes will be assessed to measure changes in cortical activity within the prefrontal cortex in response to the tACS treatment.
Timepoint [2] 307824 0
One week pre-Acute Phase, three months post-acute phase, six months post-Acute Phase, nine months post-Acute Phase and 12-months post Acute Phase (primary endpoint).
Primary outcome [3] 307825 0
Psycho-social well-being will be assessed using a comprehensive battery of composite self-report questionnaires including the FAQ, Geriatric Depression Scale, CTQ, LEC, PSS, NEO-PI-3, MSPSS, ECR-R, UCLA, and ADRI.
Timepoint [3] 307825 0
One week pre-Acute Phase and 12-months post-Acute Phase (primary endpoint).
Secondary outcome [1] 353068 0
Genotypes (DNA) implicated in Alzheimer's Disease will be examined as an exploratory outcome using a blood sample.
Timepoint [1] 353068 0
Peripheral blood samples will be collected and stored at one week pre-Acute Phase.
Secondary outcome [2] 353257 0
Epigenetic changes (methylation) and expression of genes (mRNA) will be assessed in a composite manner using a blood sample.
Timepoint [2] 353257 0
One week pre-Acute Phase each year.

Eligibility
Key inclusion criteria
(1) Meet criteria for amnestic-Mild Cognitive Impairment as defined by the International working group on mild cognitive impairment; (2) are competent to consent based on their ability to provide a spontaneous narrative description of the key elements of the study, as assessed by a clinical staff member independent of the research project; (3) are between the ages of 50 and 70; (4) are able to participate in cognitive testing in English.
Minimum age
50 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Have a DSM-IV history of substance abuse or dependence in the last 6 months; (2) have a concomitant major and unstable medical, psychiatric or neurological illness; (3) are pregnant, (4) are currently taking any medication shown to interfere with the effects of stimulation; namely benzodiazepines; or (5) have any contraindications to brain stimulation as assessed using the TMS/tACS safety screen.

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)
Device condition is coded; 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.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The study is primarily powered to detect a significant improvement in cognitive function following tACS. Single sessions of transcranial electrical stimulation have been shown to have a moderate effect size on cognition (Cohen’s d = 0.50) in older adults. Therefore, in the proposed study we are predicting that repeated sessions of tACS will result in at least a moderate to large effect size (d = 0.60); using this effect size a sample of 100 will provide greater than 95% power with an alpha of 0.05.

Recruitment
Recruitment status
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)
VIC
Recruitment hospital [1] 12205 0
The Alfred - Prahran
Recruitment hospital [2] 12373 0
Epworth Rehabilitation Camberwell - Camberwell
Recruitment postcode(s) [1] 24380 0
3004 - Prahran
Recruitment postcode(s) [2] 24381 0
3004 - St Kilda Road Melbourne
Recruitment postcode(s) [3] 24636 0
3124 - Camberwell

Funding & Sponsors
Funding source category [1] 300938 0
University
Name [1] 300938 0
Monash University
Address [1] 300938 0
Monash University
Wellington Rd, Clayton, VIC 3800
Country [1] 300938 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Wellington Rd, Clayton, VIC 3800
Country
Australia
Secondary sponsor category [1] 300551 0
None
Name [1] 300551 0
Nil
Address [1] 300551 0
Nil
Country [1] 300551 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301705 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 301705 0
The Alfred Hospital
55 Commercial Rd, Melbourne, VIC 3004
Ethics committee country [1] 301705 0
Australia
Date submitted for ethics approval [1] 301705 0
31/05/2018
Approval date [1] 301705 0
13/08/2018
Ethics approval number [1] 301705 0
274/18

Summary
Brief summary
There are many factors which are thought to contribute to the ability to maintain good brain health, including genetics, psychosocial and environmental factors. In addition, recent research has indicated that it may be possible to induce, or promote, brain health using non-invasive brain stimulation - namely transcranial Alternating Current Stimulation (tACS).

Therefore, the purpose of this project is to investigate brain activity that is related to cognitive performance (i.e. thinking skills) in people with mild cognitive impairment. We will conduct these investigations a number of times over a three-year period to allow us to look at any changes that may occur in brain activity and cognitive performance. We will also be looking at any psychosocial and environmental factors that might contribute to changes in brain activity and cognitive performance. Finally, we will also investigate the effects of tACS on brain activity and cognition over the same period of time. Overall, this project aims to help provide a better understanding of the reasons why some people with MCI go on to develop Alzheimer’s, whilst others do not, and ultimately help in the development of early intervention treatments for Alzheimer’s disease.

It is hypothesised that participants receiving active treatment will improve cognitive function, enhance brain activity, and strengthen functional brain connectivity after each yearly treatment course compared to those who undergo sham treatment. It is also hypothesised that there will be a lower conversion from MCI to Alzheimer’s disease in individuals receiving the active treatment over the three-year period, compared to those receiving the sham treatment. Finally, it is hypothesised that biopsychosocial factors will influence pathophysiological changes in people with MCI over time.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87826 0
A/Prof Kate Hoy
Address 87826 0
Monash Alfred Psychiatry Research Centre
Level 4
607 St Kilda Rd
Melbourne 3004
VIC

Epworth Centre for Innovation in Mental Health (ECIMH)
888 Toorak Rd
Melbourne 3124
VIC
Country 87826 0
Australia
Phone 87826 0
+61 3 9076 5034
Fax 87826 0
Email 87826 0
kate.hoy@monash.edu
Contact person for public queries
Name 87827 0
Ms Freya Stockman
Address 87827 0
Monash Alfred Psychiatry Research Centre
Level 4
607 St Kilda Rd
Melbourne 3004
VIC

Epworth Centre for Innovation in Mental Health (ECIMH)
888 Toorak Rd
Melbourne 3124
VIC
Country 87827 0
Australia
Phone 87827 0
+61 3 9076 9896
Fax 87827 0
Email 87827 0
freya.stockman@monash.edu
Contact person for scientific queries
Name 87828 0
A/Prof Kate Hoy
Address 87828 0
Monash Alfred Psychiatry Research Centre
Level 4
607 St Kilda Rd
Melbourne 3004
VIC

Epworth Centre for Innovation in Mental Health (ECIMH)
888 Toorak Rd
Melbourne 3124
VIC
Country 87828 0
Australia
Phone 87828 0
+61 3 9076 5034
Fax 87828 0
Email 87828 0
kate.hoy@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual participant data will not become available to other researchers.
What supporting documents are/will be available?
No other documents available
Summary results
No Results