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Trial registered on ANZCTR


Registration number
ACTRN12614001039673
Ethics application status
Approved
Date submitted
18/09/2014
Date registered
26/09/2014
Date last updated
25/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Cognitive Training and Brain Stimulation in Parkinson's Disease
Scientific title
A randomised controlled trial to evaluate the effect of cognitive training and transcranial direct current stimulation on cognitive function and quality of life in people with Parkinson's disease and mild cognitive impairment
Secondary ID [1] 285361 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 293087 0
Mild Cognitive Impairment 293088 0
Condition category
Condition code
Neurological 293363 293363 0 0
Parkinson's disease
Mental Health 293412 293412 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be invited to attend the Neurosciences Laboratory at the School of Psychology, Curtin University to complete a pre-intervention neuropsychological assessment. Upon arrival the researcher will give participants an overview of the present study, clarify doubts and answer questions that participants may have. The researcher will ask participants to carefully read through the information sheet and consent form. Upon receipt of informed consent, participants will be asked to complete 14 different neuropsychological tests assessing cognitive functioning, activities of daily living (ADL), and quality of life (QOL). Thirteen tests are paper/pencil based and one test, Stockings of Cambridge, will be completed on the Cambridge Automated Neuropsychological Test and Assessment Battery (CANTAB). The CANTAB is a touch screen tablet computer comprising a range of established neuropsychological tests. All tests have been appropriately selected and recommended for use in Parkinson's Disease (PD; see Litvan et al., 2012). Prior to each test participants will be given oral instructions outlining how to complete the test. Participants will be offered regular breaks during assessments. If a participant is showing signs of fatigue or distress and they choose to continue, they will be offered additional breaks to assist them in completing the tasks. However, due to possible learning effects participants will be unable to complete a re-test if they choose to stop an assessment. At completion participants will be thanked for their participation with a $10 gift card. Each participant’s assessment results will be appropriately scored and interpreted and those who meet the inclusion criteria (presence of Mild Cognitive Impairment) will be asked to participate in the next stage of the project.

After 90 participants have completed pre-intervention neuropsychological assessments and met the necessary inclusion criteria and transcranial direct current stimuluation (tDCS) exclusion criteria they will be asked to read an information sheet and sign a consent form for this stage of the project. Then participants will be randomised to one of six intervention groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) control. Standard cognitive training involves a set of cognitive tasks administered to participants regardless of their individually different cognitive deficits. Whereas tailored cognitive training is customised to address specific cognitive impairments of the individual (e.g., memory, language, executive functions). Participants allocated to the cognitive training groups will complete three 45-minute sessions of in-home computer-based cognitive training per week for 4-weeks. Cognitive training will be competed using the Smartbrain Pro program (www.smartbrain.com) and streamed via Optus Mini Wifi modems onto Pendo Pad tablets. During the first week the researcher will visit participants to set up the equipment, teach them how to use the program, answer questions, and ensure they are able to complete the activities. From weeks two to four the researcher will make follow-up telephone calls to ensure participants are complying with the training and assist them with any issues they may be experiencing. Participants allocated to the groups completing tDCS will complete 4-sessions of tDCS over 4-weeks (1-session per week). tDCS sessions will be delivered by a constant current stimulator (Empi) and involve 30 minutes of constant current 2mA stimulation (equivalent to 0.08 Ma/CM2) over their left dorsal lateral prefrontal cortex, administered with two 35 cm2 sponge electrodes soaked in saline solution. To stimulate the left dorsal lateral prefrontal cortex, the anode electrode will be placed over F3 according to the 10–20 international system for EEG electrodes placement. There will be a period of 30 seconds at the start and end of tDCS for ramp up/ramp down. Participants will relax (read a magazine, have a cup of tea) during each tDCS session. Participants allocated to the cognitive training + tDCS groups will complete the previously described activities simultaneously for 4-weeks. At completion of the 4-week cognitive training and tDCS interventions, participants will complete the same neuropsychological tests (as pre-intervention) at post-intervention and 3-month follow-up.

Participants may experience cognitive fatigue during neuropsychological assessments and cognitive training. However, regular breaks will be offered during assessments and Smartbrain Pro creators recommend no more than 45-minutes of cognitive training to reduce the likelihood of fatigue. The use of tDCS in the present study involves a single 9-volt battery to apply a constant current (usually one millivolt) for a set period of time (30 minutes). The current is passed through rubber electrodes (6 cm x 4 cm) placed inside sponge containers moistened with water. The use of large electrodes (with an area of 24 cm2) ensures that current density is well below levels that might be perceived as unpleasant or painful. The density of 0.08 mA/cm2 is in the lower range of that used in the research studies published to date (Boggio et al., 2006; Nitsche et al., 2008). Participants might experience a tingling sensation under an electrode at the onset of stimulation but this sensation quickly fades. The procedure is safe, and no significant adverse events have been reported with low current densities (from 0.03 to 0.08 mA/cm2). The stimulation in the proposed research will be applied for 30 minutes (during which no task is required of the participant) with a current density of 0.08 mA/cm2. Stimulation can cause a feeling of nausea if one of the electrodes is positioned over a mastoid process (the bony prominence behind the ear). This location, which can activate the vestibular system (the organ of balance), will be avoided in this project. The safety of tDCS is discussed by Nitsche et al. (2008) and the tDCS protocol to be used in this study adheres to all safety recommendations. The researchers will adhere to a strict administration and adverse event protocols. The researchers will ask participants how they are feeling during the tDCS phase and will remain with the participant at all times. The researchers will be first-aid trained to cope with any (unlikely) issues and the laboratory has a telephone. If at any point the participant experiences any adverse effects during neuropsychological assessments, cognitive training, or tDCS, the procedures will cease. All assessments and interventions will be completed when participants are in 'ON' stage of medication use (approximately 1-hour post medication) to ensure they are feeling their best. At completion of follow-up assessments participants will be given a $15 gift card to thank them for participating in the research.
Intervention code [1] 290276 0
Rehabilitation
Intervention code [2] 290319 0
Treatment: Other
Comparator / control treatment
No treatment
Control group
Active

Outcomes
Primary outcome [1] 293190 0
Cognitive Functioning - Measured by the Mini Mental State Examination, Parkinson's Disease-Cognitive Rating Scale, Australian National Adult Reading Test (baseline only), Hopkins Verbal Learning Test-Revised, Judgement of Line Orientation, Boston Naming Test, Rivermead Paragraph Recall Subtest, Letter Number Sequencing, Controlled Oral Word Association, Similarities, Hooper Visual Organisation Test, Stockings of Cambridge, and Stroop Colour-Word Test.
Timepoint [1] 293190 0
Baseline, and at 1 and 12-weeks after intervention commencement.
Primary outcome [2] 293191 0
Activities of Daily Living - Measure by the Unified Parkinson's Disease Rating Scale (Section 2 - ADL).
Timepoint [2] 293191 0
Baseline, and at 1 and 12-weeks after intervention commencement.
Primary outcome [3] 293192 0
Quality of Life - Measured by the Parkinson's Disease Questionnaire-39.
Timepoint [3] 293192 0
Baseline, and at 1 and 12-weeks after intervention commencement.
Secondary outcome [1] 310557 0
Mood - Measured by the Depression, Anxiety, and Stress Scale-21.
Timepoint [1] 310557 0
Baseline, and at 1 and 12-weeks after intervention commencement.

Eligibility
Key inclusion criteria
Individuals must meet the following criteria to be eligible to participate in the study: 1) diagnosed with idiopathic Parkinson's Disease by a neurologist or geriatrician in accord with the Unite Kingdom Parkinson's Disease Society Brain Bank Clinical (UKPDSBBC) criteria; 2) describe self-reported problems with cognition which do not significantly impact on functional independence; 3) presence of mild cognitive impairment in accord with the Movement Disorders Society Level II diagnostic criteria; 4) stable response to antiparkinsonian medication for a minimum period of 2 months.
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Individuals will be excluded from the study in they meet the following criteria: 1) presence of Parkinson's Disease-Dementia; 2) below average premorbid intelligence; 3) history of brain surgery; 4) a deep brain stimulation (DBS) implant; 5) history of epilepsy; 6) any active skin disease on the scalp; 7) unstable medical condition (Parkinson’s is not classified as an unstable condition); 8) currently taking psychoactive medication (Parkinson’s medication will not impact TDCS); 9) history of migraine; 10) history of episodes of faintness; 11) history of asthma; 12) any metal implants in the head/brain; 13) 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)
Allocation concealment will be done by a researcher "off-site" to the screening and selection laboratory.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be allocated to each group through block randomisation. A computer generated randomisation list will be used to allocate participants to groups at a ratio of 1:1.
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
Previous cognitive training interventions in Pakinson's Disease found a moderate to large effect size (Naismith et al., 2013; Paris et al., 2011). An a priori power analysis was calculated using G*Power (Faul, Erdfelder, Lang, & Buchner, 2007), 54 participants will be required to detect a moderate effect (power = .80, a = .05). To reduce the impact of potential participant attrition on the power of the study, 90 participants (15 per group) will be targeted for recruitment.

Generalised linear mixed models (GLMMs) will be used to determine whether the cognitive training and tDCS groups demonstrate improvements on outcome measures compared to the control group (Bryk & Raudenbush, 1987). The GENLINMIXED procedure in SPSS (Version 22) will be used to complete the GLMMs. GLMMs are able to control for outcome variables with non-normal distributions and include both random and fixed effects (McCulloch, 2006). For the present study, there is one random effect (participant) and three fixed effects: Group (standard training vs tailored training vs tDCS vs standard training + tDCS vs tailored training + tDCS vs control), time (pre, post, follow-up) and the Group x Time interaction (McCulloch, 2006). Separate GLMMs will be run for each outcome variable to optimise the likelihood of convergence (McCulloch, 2006). However, independently analysing outcome variables will increase the Type 1 error rate. Therefore, outcome variables will be grouped (e.g., executive function measures, memory measures) and a more stringent alpha level will be applied to conserve statistical power. Unlike repeated measures ANOVA, GLMMs do not rely on participants providing data at pre/post-intervention and follow-up. GLMMs use all data available at assessment points which reduces the impact of participant attrition on statistical power. Moreover, GLMM is rigorous against unequal groups (Krueger & Tian, 2004).

Recruitment
Recruitment status
Completed
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)
WA

Funding & Sponsors
Funding source category [1] 289978 0
University
Name [1] 289978 0
Curtin University
Address [1] 289978 0
Kent Street, Bentley
Perth, Western Australia
6102
Country [1] 289978 0
Australia
Primary sponsor type
Individual
Name
Blake Lawrence
Address
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Country
Australia
Secondary sponsor category [1] 288664 0
Individual
Name [1] 288664 0
Dr Andrea Loftus
Address [1] 288664 0
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Country [1] 288664 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291688 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 291688 0
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Ethics committee country [1] 291688 0
Australia
Date submitted for ethics approval [1] 291688 0
Approval date [1] 291688 0
11/09/2014
Ethics approval number [1] 291688 0
4806

Summary
Brief summary
This study will investigate standard brain training, tailored brain training, and brain stimulation for improving cognitive functioning in people with Parkinson's Disease and Mild Cognitive Impairment. It is predicted that tailored brain training will improve cognitive functioning to a greater extent than standard brain training. It is also predicted that tailored brain training combined with brain stimulation will lead to even greater improvements in cognitive functioning. Findings from this study will provide valuable information into the therapeutic potential of brain training and stimulation for people with Parkinson's Disease and Mild Cognitive Impairment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51510 0
Mr Blake Lawrence
Address 51510 0
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Country 51510 0
Australia
Phone 51510 0
+61 0415621061
Fax 51510 0
Email 51510 0
blake.lawrence@postgrad.curtin.edu.au
Contact person for public queries
Name 51511 0
Mr Blake Lawrence
Address 51511 0
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Country 51511 0
Australia
Phone 51511 0
+61 0415621061
Fax 51511 0
Email 51511 0
blake.lawrence@postgrad.curtin.edu.au
Contact person for scientific queries
Name 51512 0
Mr Blake Lawrence
Address 51512 0
Curtin University
Kent Street, Bentley
Perth, Western Australia
6102
Country 51512 0
Australia
Phone 51512 0
+61 0415621061
Fax 51512 0
Email 51512 0
blake.lawrence@postgrad.curtin.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary