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Trial registered on ANZCTR


Registration number
ACTRN12619000455167
Ethics application status
Approved
Date submitted
27/02/2019
Date registered
20/03/2019
Date last updated
20/03/2019
Date data sharing statement initially provided
20/03/2019
Date results information initially provided
20/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Non-pharmacological interventions for improving behaviour in children with AD/HD.
Scientific title
Comparing behavioural, executive function, and EEG outcome effects of three non-pharmacological interventions in children with AD/HD: a single case experimental design.
Secondary ID [1] 297552 0
None
Universal Trial Number (UTN)
U1111-1229-3353
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Attention deficit hyperactivity disorder 311775 0
Condition category
Condition code
Mental Health 310388 310388 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The current study compared the transfer effects of three promising training protocols for reducing symptoms in children with AD/HD. (1) cognitive training (CT), (2) neurofeedback training (NFT), and (3) the CT combined with the NFT.

Each participant was randomised to one of the three training conditions. Each case completed a baseline phase followed by an intervention phase. Participants and their parents were not informed that there were two phases across sessions.

Training phases

In the intervention phase, participants were required to complete 20 training
sessions at home over 7 weeks. They completed 3 sessions (on Monday, Wednesday, and
Friday) per week for the first six weeks and 2 sessions (on Wednesday and Friday) in the
last week. Each training session took about 25 minutes to complete. The intervention
was completed on a 7-inch tablet device and delivered by a combination of software (i.e.
the Focus Pocus software program) and EEG hardware (i.e. the NeuroSky Mindwave
Mobile EEG device).

The training software was fully introduced in other papers (e.g. Jiang & Johnstone, 2015; Johnstone et al., 2017). Briefly, different types of training are delivered as games and difficulty levels are adaptive. Each training session consisted of 14 games in the current study. The CT condition consisted of working memory (WM) games and response inhibition (RI) games, the NFT condition consisted of frontal EEG alpha wave and beta wave games, and the combined condition consisted of both the two types of games.

The baseline duration was predetermined. Within each training condition, the duration for the first 3 cases was randomised from 2-weeks, 3-weeks, and 4-weeks without replacement, and the duration for the last case was randomised from 2-weeks, 3-weeks, and 4-weeks.

Adherence to the intervention was monitored with device/application analytics.
Intervention code [1] 313784 0
Treatment: Other
Comparator / control treatment
The baseline phase provided the experimental control. An active control was adopted to maximize internal experimental validity (e.g. expectation). In the baseline phase, participants were required to wear the portable EEG device and to complete strategy games on the tablet. The “training” frequency and length on the strategy games was the same as in the intervention phase; 25 minutes per session and 3 sessions per week.
Control group
Active

Outcomes
Primary outcome [1] 319268 0
The ADHD Rating Scale was used to derive AD/HD symptom ratings by parents.

DuPaul, G. J.; Power, T. J.; Anastopoulos, A. D.; Reid, R. (1998). ADHD Rating Scale-IV: Checklists, norms, and clinical interpretation. New York: Guilford.
Timepoint [1] 319268 0
Weekly for 13 weeks
Primary outcome [2] 319269 0
Executive function task performance. EFs were assessed via a computer task measuring WM and another measuring RI, and a questionnaire to measure the everyday performance of WM (EWM) and RI (ERI). In contrast to the CT training games within Focus Pocus, these assessment tasks were not gamified and they assessed similar processes but with none of the same surface features. WM was measured by the 2-back task (Jaeggi et al., 2010) and RI measured by the Stop-signal task (Logan et al., 2014). Performance accuracy on the 2-back task and the stop-signal reaction time from the stop-signal task were selected as dependent variables. The Behavior Rating Inventory of Executive Function (BRIEF) parent version was used to measure EWM and ERI (Gioia et al., 2000), with consideration of the raw scores of the two subscales.
Timepoint [2] 319269 0
Weekly for 13 weeks.
Secondary outcome [1] 367523 0
Brain electrical activity (EEG). Baseline arousal (absolute alpha power averaged across channels in the eyes-closed condition, as per Barry et al., 2008), fronto-central theta/beta ratio (TBR, obtained by averaging the ratio of FC5 and FC6), frontal alpha (absolute alpha power averaged in AF3, F7, F3, F4, F8, and AF4) and frontal beta (absolute beta power averaged by AF3, F7, F3, F4, F8, and AF4) were selected as the dependent variables.
Timepoint [1] 367523 0
Weekly for 13 weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

1) screened by the Clinical Diagnostic Interviewing Scales (Barkley, 1998), a structured clinical interview based on the DSM-IV;

2) no history of head trauma with loss of consciousness

3) no history of neurological illness or other severe disease

4) no history of other psychiatric disorders described in the DSM-IV

5) naïve to any pharmacological treatment for AD/HD

6) an IQ higher than 80 on the Wechsler Intelligence Scale III for children.
Minimum age
7 Years
Maximum age
12 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No professional diagnosis of AD/HD.

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)
Children were randomly assigned to a condition, based on a random permutation
calculator (http://www.randomizer.org). Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequencing was determined by random permutation calculator (http://www.randomizer.org).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Other
Other design features
Participants were randomly allocated to one of the three training conditions.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A single-case experimental design (SCED) was used, with 12 cases. Visual analysis is frequently used in SCED research, with a focus on specific features to examine intervention effects (WWC, 2014). Elements of the analysis include: 1) Level – the mean score for the data within a phase, 2) Trend – the slope for the data within a phase, and 3) Variability – the range or standard deviation of data within a phase. Next, features that show the difference between phases are examined: 4) Immediacy – the change between the level of the last three observation points in one phase and that of the first three observation points in next phase, 5) Overlap – the proportion of data between
phases overlapped, and 6) Consistency – the consistency of data in similar phases.

Although often used in SCED, visual analysis has been criticized for lacking
decision guidelines, being potentially biased by trends in the baseline phases, insensitivity
to subtle changes, and lacking any effect size indicators (Harrington & Velicer, 2015).
The shortcomings have motivated the development of statistical analysis techniques for
used in SCED research. Tau-U is one such statistical method, based on nonparametric
inference, combining non-overlap and trend analysis (Parker et al., 2011). The broad
rational of this analysis technique is that there should be little or no overlap between data
in the baseline and intervention phases if the intervention is showing an effect. Also, the technique examines any trends in the baseline phase and can correct for this in the phase
comparison.

While compared to visual analysis Tau-U provides a more objective and sensitive
way to detect intervention effects (Parker et al., 2011), it does not provide information
about immediacy of the effect; which is of interest in CT and NFT research. Hence, in
the current study Tau-U analysis was firstly conducted to detect the intervention effects,
with visual analysis used as an adjunct analysis to examine the immediacy of the effect.
Also, the level and the consistency were also examined to recheck any detected effects.

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 outside Australia
Country [1] 21319 0
China
State/province [1] 21319 0
Beijing

Funding & Sponsors
Funding source category [1] 302106 0
University
Name [1] 302106 0
University of Wollongong
Address [1] 302106 0
Northfields Avenue, Wollongong, NSW 2522.
Country [1] 302106 0
Australia
Primary sponsor type
University
Name
Peking University Sixth Hospital
Address
51 Huayuan N Rd, Haidian Qu, Beijing Shi, China, 100083
Country
China
Secondary sponsor category [1] 301936 0
None
Name [1] 301936 0
Address [1] 301936 0
Country [1] 301936 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302784 0
Ethics Committee of Peking University Health Science Centre
Ethics committee address [1] 302784 0
51 Huayuan N Rd, Haidian Qu, Beijing Shi, China, 100083
Ethics committee country [1] 302784 0
China
Date submitted for ethics approval [1] 302784 0
01/08/2016
Approval date [1] 302784 0
03/10/2016
Ethics approval number [1] 302784 0
Unknown
Ethics committee name [2] 302785 0
University of Wollongong Human Research Ethics Committee
Ethics committee address [2] 302785 0
Northfields Avenue, Wollongong, NSW 2522.
Ethics committee country [2] 302785 0
Australia
Date submitted for ethics approval [2] 302785 0
06/06/2016
Approval date [2] 302785 0
25/07/2016
Ethics approval number [2] 302785 0
HE 16/032

Summary
Brief summary
The increasing understanding of Attention-deficit/Hyperactivity Disorder (AD/HD)
lays the foundations for developing new treatments. A single-case experimental design with 12 case was planned. The current study compared the transfer effects of three promising training protocols – cognitive training (CT), neurofeedback training (NFT), and the CT combined with the NFT. Outcome measures include overt behaviour, brain electrical activity, and executive function task performance.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91394 0
Prof Stuart Johnstone
Address 91394 0
Northfields Avenue, School of Psychology, University of Wollongong, Wollongong, NSW 2522.
Country 91394 0
Australia
Phone 91394 0
+61 2 4221 4495
Fax 91394 0
+61 2 4221 4163
Email 91394 0
sjohnsto@uow.edu.au
Contact person for public queries
Name 91395 0
Prof Stuart Johnstone
Address 91395 0
Northfields Avenue, School of Psychology, University of Wollongong, Wollongong, NSW 2522.
Country 91395 0
Australia
Phone 91395 0
+61 2 4221 4495
Fax 91395 0
+61 2 4221 4163
Email 91395 0
sjohnsto@uow.edu.au
Contact person for scientific queries
Name 91396 0
Prof Stuart Johnstone
Address 91396 0
Northfields Avenue, School of Psychology, University of Wollongong, Wollongong, NSW 2522.
Country 91396 0
Australia
Phone 91396 0
+61 2 4221 4495
Fax 91396 0
+61 2 4221 4163
Email 91396 0
sjohnsto@uow.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The nature of the data is personal and it is not appropriate for it to be made available to the public. Confidentiality has been assured in the ethics approval.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
The results showed that the CT condition improved inhibitory function in day-to-day
situations, the NFT condition improve alpha activity, and the combined condition had no
transfer effect.