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Trial registered on ANZCTR


Registration number
ACTRN12618000999235
Ethics application status
Approved
Date submitted
12/06/2018
Date registered
14/06/2018
Date last updated
1/06/2024
Date data sharing statement initially provided
9/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised control trial of cognitive training and non-invasive brain stimulation in Parkinson's: The impact on cognition (thinking skills) and quality of life.
Scientific title
A randomised control trial of cognitive training and non-invasive brain stimulation in PD: The
impact on cognition and quality of life.
Secondary ID [1] 295172 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's disease 308299 0
Mild Cognitive Impairment 308300 0
Condition category
Condition code
Neurological 307305 307305 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will use a dual-protocol intervention combining cognitive training and transcranial direct current stimulation (tDCS). These two interventions will be conducted simultaneously in each session. Upon study entry, participants will be assigned to one of the following 4 groups:
1. Anodal (active) tDCS and cognitive training (active)
2. Sham (control) tDCS and cognitive training (active)
3. Anodal (active) tDCS and placebo (control) cognitive training
4. Sham (control) tDCS and placebo (control) cognitive training.

ARM 1 - Active Cognitive Training
Participants in the active cognitive training groups (1 and 2) will complete cognitive training. Cognitive training will be conducted using MyBrainTrainerTM, a commercially available cognitive training package that runs via an online website. Participants will complete two 20-minute intervention sessions per week for 4-weeks (a total of 8 sessions). Jean, Bergeron, Thivierge, and Simard (2010) suggest that for people with MCI, 5 to 15 cognitive training sessions completed in less than 12 weeks are equally efficacious as longer and more costly interventions. In our experience, participants are likely to demonstrate fatigue after approximately 30 minutes of cognitive training which may impact their performance, hence the restricted duration of the intervention. Participants will complete a predetermined cognitive training program comprising five different exercises. These activities will include one short-term memory exercise, one executive function exercise, one information processing exercise, one working memory exercise, and one visual spatial exercise. Each exercise lasts approximately 3 – 4 minutes (depending on speed of response) and has a function for demonstration of the exercise before commencement. The program will halt after 20 minutes of training. In week one, participants will complete 2 identical training sessions comprising the 5 exercises at beginner’s level (sessions 1 and 2). In weeks 2 and 3, participants will complete 4 identical training sessions comprising the 5 exercises at intermediate level (sessions 3, 4, 5, and 6). In week 4, will complete 2 identical training sessions comprising the 5 exercises at advanced level (sessions 7 and 8) Online feedback (i.e. during the trials) will not be provided to the participant for any of the exercises, as this will help to reduce the risk of any distress associated with performance. Participants’ performance will be automatically monitored and recorded by the program, giving us an indication of the effectiveness of the training for each participant. For all exercises in all sessions, the researcher will provide verbal instructions and an example trial to demonstrate the task. Before commencing each exercise, the researcher will ask the participant if they understand the task and will give the participant an opportunity to ask questions about the instructions and, if required, demonstrate the task again. The program also provides written instructions on the screen just prior to commencement of the exercise. This intervention will be delivered by the project research assistant who has over 5 years experience with working in Parkinson's intervention trials. The research assistant is a psychology graduate. The intervention will be provided face-to-face and individually.

ARM 2 - Active tDCS
Participants in the active tDCS groups (the anodal (active) groups 1 and 3) will receive 20 minutes of constant current 1.5 mA (equivalent to 0.08 mA/cm2). Stimulation over the left dorsal lateral prefrontal cortex (DLPFC). This level is consistent with safety guidelines (Nitsche et al., 2008) and is well tolerated in those with PD-MCI (Lawrence et al., 2018). tDCS will be delivered by a constant current stimulator (Soterix®), which is administered using two 35 cm 2 sponge electrodes that have been soaked in saline solution. The anode electrode will be placed over F3 according to the 10-20 international system for EEG electrode placement, to stimulate the left DLPFC. The cathode (neutral) electrode will be position on the left side of the forehead. There will be a period of 30 seconds at the beginning and end of the tDCS for ramp up/down. tDCS will be delivered at the same time the participant is completing the cognitive training such that tDCS and cognitive training occur simultaneously for 20 minutes. This intervention will be administered by the project research assistant (as above) who is fully trained on the the set-up and administration of tDCS, and has previously completed a similar study as part of her Phd. The intervention will be delivered face-to-face and individually.
Intervention code [1] 301510 0
Treatment: Devices
Intervention code [2] 301511 0
Treatment: Other
Comparator / control treatment
ARM 1 - Placebo Cognitive Training
Participants in the control cognitive training groups (groups 3 and 4) will complete placebo (control) cognitive training, in order to provide a true control comparison for the cognitive training groups. Participants in these placebo training groups will complete 20 minutes of restricted (basic) cognitive training. Participants will complete a pre-determined cognitive training program comprising 5 different activities (as per the cognitive training groups). However, participants will only perform the beginner versions of these exercises and will not progress through levels. Hence, all 8 sessions of placebo cognitive training will be restricted to the beginner versions of the exercises (comparable to week 1 of the cognitive training groups).

ARM 2 - Sham tDCS
Participants in the control tDCS groups (sham (control) tDCS groups 2 and 4) will experience the 30-second ramp up/down of tDCS, but stimulation will discontinue after 30 seconds. This ensures participants are unaware that they are receiving sham tDCS. tDCS will be delivered at the same time the participant is completing the cognitive training (or placebo cognitive training), such that tDCS and cognitive training occur simultaneously for 20 minutes.
Control group
Placebo

Outcomes
Primary outcome [1] 306264 0
Mild Cognitive Impairment Scores (as measured using the Movement Disorder Society Level II Diagnostic Criteria for Parkinson's disease - Mild Cognitive Impairment).
This involves two measures for each of five domains:
1. Letter-Number Sequencing subtest from the Wechsler Adult Intelligence Scale-IV (WAIS-IV; attention & working memory)
2. Stroop (Colour-Word) Test (attention)
3. CANTAB Stockings of Cambridge subtest (executive function)
4. Controlled Oral Word Association Task (executive function)
5. Boston Naming Test (language)
6. Similarities subtest of the WAIS-IV (language)
7. Hopkins Verbal Learning Test-Revised (memory)
8. Location Learning Test (memory)
9. Judgement of Line Orientation Test (visuo-spatial)
10. Hooper Visual Organisation Test (visuo-spatial)
Timepoint [1] 306264 0
1. Baseline (1 week prior to intervention)
2. Post-Intervention (1 week after intervention) [Primary Timepoint]
3. Follow-up (12 weeks after intervention)
Secondary outcome [1] 348019 0
Means scores Parkinson's Disease Questionnaire 39 (PDQ-39)
Timepoint [1] 348019 0
1. Baseline (1 week prior to intervention)
2. Post-Intervention (1 week after intervention)
3. Follow-up (12 weeks after intervention)

Eligibility
Key inclusion criteria
1) Diagnosed with idiopathic PD by a neurologist or geriatrician in accordance with the
United Kingdom Parkinson’s Disease Society Brain Bank Clinical (UKPDSBBC) criteria.
2) Self-reported problems with cognition which do not significantly impact on functional
independence.
3) Presence of MCI in accordance with the MDS PD-MCI Level II diagnostic criteria, using an SD level of 1.5.
4) Stable response to antiparkinsonian medication for a minimum period of 2 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Presence of PD-Dementia.
2) Recent history of brain surgery.
3) Deep Brain Stimulation (DBS) implant.
4) Active skin disease on the scalp.
5) History of migraine.
6) History of epilepsy.
7) Unstable medical condition (e.g., uncontrolled diabetes)
8) Metal implants in the head/brain.
9) Currently using a hearing aid.

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)
Randomisation by computer

The study research assistance will detemine if a potential participant is eligible to participate in the study. Once determined as eligible the researcher will use a block randomisation program to allocate participants to groups. At the time of determining eligibility to participate the researcher will not know to which group the participant will be assigned.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted Block Randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The target population is people with Parkinson's disease who have mild cognitive impairment. A total of 48 participants (12 per group) will take part in the study. To account for potential attrition, we aim to recruit 52 participants. Previous studies of cognitive training for Parkinson's have reported a moderate effect size in samples of 40-50 participants (Paris et al., 2011; Naismith et al., 2013).

SPSS (Version 24) will be used to calculate descriptive statistics for demographic data and
neuropsychological test scores. Frequency estimates will be calculated to describe the prevalence of MDS PD-MCI subtypes (single or multiple domain) and the prevalence of individual cognitive impairments across the five domains (memory, attention/working memory, executive function, visuospatial abilities, and language). Final analysis will involve Structural Equation Modelling (using MPlus), allowing us to determine the effect of the intervention on a range of outcome measures.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
27/08/2018
Actual
7/01/2019
Date of last participant enrolment
Anticipated
30/11/2025
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
45
Accrual to date
35
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 299760 0
Charities/Societies/Foundations
Name [1] 299760 0
Parkinson's Western Australia
Country [1] 299760 0
Australia
Primary sponsor type
Individual
Name
Professor Natalie Gasson
Address
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA 6845
Country
Australia
Secondary sponsor category [1] 299100 0
Other Collaborative groups
Name [1] 299100 0
Associate Professor Andrea Loftus
Address [1] 299100 0
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA 6845
Country [1] 299100 0
Australia
Other collaborator category [1] 280177 0
Individual
Name [1] 280177 0
Professor Romola Bucks
Address [1] 280177 0
Pro Vice Chancellor Health and Medical Research
University of Western Australia
35 Stirling Highway
Crawley, WA, 6009
Country [1] 280177 0
Australia
Other collaborator category [2] 280178 0
Individual
Name [2] 280178 0
Dr Blake Lawrence
Address [2] 280178 0
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA 6845
Country [2] 280178 0
Australia
Other collaborator category [3] 280180 0
Individual
Name [3] 280180 0
Dr Meghan Thomas
Address [3] 280180 0
Head of Clinical Development
Argenica Therapeutics
4/117 Broadway
Nedlands, WA 6009
Country [3] 280180 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300651 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 300651 0
Research Office
Curtin University
Building 100, Level 2 West
Kent Street
Bentley, Western Australia 6102
Ethics committee country [1] 300651 0
Australia
Date submitted for ethics approval [1] 300651 0
15/06/2018
Approval date [1] 300651 0
21/08/2018
Ethics approval number [1] 300651 0

Summary
Brief summary
Research has demonstrated that people with Parkinson’s (PD) and mild cognitive impairment (PD- MCI) can improve their cognitive functioning using both cognitive training and transcranial direct current stimulation (tDCS) independently (e.g., Hindle et al., 2013). Pilot research by Lawrence and colleagues (2018), in this laboratory, suggests that the most effective improvement of PD-MCI occurs following cognitive training coupled with tDCS (compared to either intervention alone), where cognitive training was performed for 2 days per week and tDCS was delivered once per week (on a separate day to the training). The current study will extend these findings by adopting a randomised control trial approach to examine the impact of concurrent tDCS delivery and cognitive training on PD-MCI (that is, both interventions delivered at the same time).
This study will examine the impact of standard cognitive training coupled with anodal tDCS over the left dorso-lateral prefrontal cortex (DLPFC) on cognition and quality of life (QOL), after controlling for self-reported sleep, hearing loss, motor symptoms, and mood in PD. A baseline assessment of motor and cognitive symptoms of PD, QOL, sleep, hearing loss, and mood will be completed 1 week prior to the intervention. Participants will be randomly assigned to 1 of 4 groups; (1) anodal (active) tDCS and cognitive training, (2) sham (control) tDCS and cognitive training, (3) anodal (active) tDCS and placebo (control) cognitive training, or (4) sham (control) tDCS and placebo (control) cognitive training. Participants in group 1 will receive 30 minutes of constant 1.5 mA stimulation over the left dorso-lateral prefrontal cortex (DLPFC) whilst simultaneously completing the cognitive training. Participants in group 2 will receive 30 minutes of sham (control) tDCS over left DLPFC whilst simultaneously completing the cognitive training. Participants in group 3 will receive 30 minutes of constant 1.5 mA stimulation over left DLPFC whilst simultaneously completing placebo cognitive training. Group 4 will receive 30 minutes of sham (control) tDCS over left DLPFC whilst simultaneously completing placebo cognitive training.
Participants will complete two intervention sessions a week for 4 weeks, resulting in 8 sessions in total. Participants will complete post-intervention measures as at baseline, 1 and 12 weeks post-intervention. Participants will then complete a follow-up assessment at 12 weeks post-cessation.
It is hypothesised that the participants receiving both active treatments concurrently will perform better on the cognitive measures and will report higher quality of life than participants receiving just one active treatment. In addition, participants receiving no active treatments will perform more poorly on the cognitive measures and report lower quality of life that participants receiving one or both active treatments.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84342 0
Prof Natalie Gasson
Address 84342 0
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA, 6845
Country 84342 0
Australia
Phone 84342 0
+618 9266 4308
Fax 84342 0
+618 9266 2464
Email 84342 0
[email protected]
Contact person for public queries
Name 84343 0
Natalie Gasson
Address 84343 0
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA, 6845
Country 84343 0
Australia
Phone 84343 0
+618 9266 4308
Fax 84343 0
+618 9266 2464
Email 84343 0
[email protected]
Contact person for scientific queries
Name 84344 0
Natalie Gasson
Address 84344 0
Discipline of Psychology
School of Population Health
Curtin University
GPO Box U1987
Perth, WA, 6845
Country 84344 0
Australia
Phone 84344 0
+618 9266 4308
Fax 84344 0
+618 9266 2464
Email 84344 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
Ethics approval does not allow for data sharing.


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.