Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001045404
Ethics application status
Approved
Date submitted
10/11/2015
Date registered
5/08/2016
Date last updated
13/06/2019
Date data sharing statement initially provided
17/04/2019
Date results information initially provided
13/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial to evaluate the safety and efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to improve cognitive flexibility and emotional self-regulation in young people with autism spectrum disorder
Scientific title
A clinical trial to evaluate the safety and efficacy of high-definition transcranial direct current stimulation (HD-tDCS) using a probabilistic reversal task and a cognitive reappraisal task combined with electroencephalography to improve cognitive flexibility and emotional self-regulation in young people with autism spectrum disorders.
Secondary ID [1] 287649 0
None
Universal Trial Number (UTN)
U1111-1175-8550
Trial acronym
N/A
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorders 296481 0
Condition category
Condition code
Mental Health 296738 296738 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study involves the use of high-definition transcranial direct current stimulation (HD-tDCS) over the ventrolateral prefrontal cortex to improve cognitive flexibility and emotional self-regulation in young people with autism spectrum disorder (ASD).
The intervention frequency will be one session of 20 minutes of HD-tDCS for 4 consecutive days. The intensity of the total injected current is 1.693 milliamps (mA). It includes a ramp-up and rump-down period of 30 seconds. This is a double blind study where twenty participants will receive both active and sham (placebo) stimulation. These two stimulations conditions will be randomized across participants, and there will be a 4-week washout period in between. HD-tDCS involves a weak electrical current applied to the brain area of interest via small electrodes placed on the scalp.
A trained expert in non-invasive brain stimulation techniques with a first aid accreditation will administer the HD-tDCS.
A safety HD-tDCS protocol will be given to participants before and after each session.
Intervention code [1] 293049 0
Treatment: Devices
Comparator / control treatment
The control treatment consists in the administration of sham (placebo) HD-tDCS stimulation over the ventrolateral prefrontal cortex, the same brain region used for the active treatment.
Sham treatment will be administered for 20 minutes, same as the active treatment.
TDCS sham procedures consist in switching off the stimulator after 30 s of the stimulation, this has been shown to be effective as subjects failed to discern between active and sham stimulation.
Control group
Placebo

Outcomes
Primary outcome [1] 296354 0
Changes in electroencephalography components when conducting a probabilistic reversal task. Specifically, changes in feedback related negativity (FRN) component of the probabilistic reversal task will be investigated as our primary outcome measure. The version of the probabilistic reversal learning task used in this clinical trial can be found in Chase el al., 2011, Journal of Cognitive Neuroscience.

Timepoint [1] 296354 0
Active HD-tDCS: Baseline, 1 day after last treatment session (day 5),
Sham (placebo) HD-tDCS: BASELINE, 1 day after last treatment session (day 5),
Primary outcome [2] 298992 0
Changes in electroencephalography components when conducting a cognitive reappraisal task which measures emotional self-regulation tasks. Specifically, changes in the amplitude of the late positive potential (LPP) of the cognitive reappraisal task will be investigated as our primary outcome measures. The cognitive reappraisal task is a well validated task that has been used in many research studies to measure emotional regulation (Feeser et al., 2014). For this clinical trial we will use a similar version seen in Parvaz et al., 2012, Cognitive Affective Behavioural Neuroscience,

Timepoint [2] 298992 0
Active HD-tDCS: Baseline, 1 day after last treatment session (day 5).
Sham (placebo) HD-tDCS: BASELINE, 1 day after last treatment session (day 5),
Secondary outcome [1] 318230 0
Global executive functioning assessed using the Behavior Rating Inventory of Executive Function - Adult Version "Trademark" (BRIEF-A "Trademark"),
Timepoint [1] 318230 0
Active HD-tDCS: Baseline, 1 day after last treatment session (day 5), 2 weeks after last treatment session (day 14).

Sham (placebo) HD-tDCS: BASELINE, 1 day after last treatment session (day 5), 2 weeks after last treatment session (day 14).
Secondary outcome [2] 325833 0
Repetitive behaviours assessed using the REPETITIVE BEHAVIOR SCALE – Revised (RBS-R).
Timepoint [2] 325833 0
Active HD-tDCS: Baseline, 1 day after last treatment session (day 5), 2 weeks after last treatment session (day 14).

Sham HD-tDCS: Baseline, 1 day after last treatment session (day 5), 2 weeks after last treatment session (day 14).
Secondary outcome [3] 325834 0
Autism symptoms assessed using the Social Responsiveness Scale "Trademark" (SRS "Trademark") .
Timepoint [3] 325834 0
Baseline, 1 week post first treatment session (day 8) and one month post first treatment session (day 30).

Eligibility
Key inclusion criteria
Right and left handed individuals with a diagnosis of autism spectrum disorder with mild intellectual ability or higher (IQ>55).
Stable medication regime for at least 4 weeks, and stable throughout duration of enrolment in study.
Minimum age
16 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Participants whose primary language is other than English.
- Pregnant women.
- Participants <16 years old.
- Participants with metal implants in their heads.
- Major medical or neurological condition

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)
Treatment allocation concealment will be achieved by using a password protected computer program, implemented by a member of the Cognitive Neuroscience Unit at Deakin University who will inform the principal investigator of the outcome via email.
The person who will determine the eligibility of the participants will be unaware of which stimulation will be given in each of the two treatment weeks.
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 assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size of 40 participants will be reduced to 20. After doing the appropriate power analysis, results revealed that a sample of 20 participants provides 85% power to detect a true effect. The consultant biostatistician performing the analyses will be blind to participants’ order of allocation to treatment groups. Descriptive analyses will be used to characterise demographic and outcome variables (t-test, squared chi or ANOVAs). Mainly, a repeated measures ANOVA will be used to test the study hypothesis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
20/04/2018
Actual
11/05/2018
Date of last participant enrolment
Anticipated
15/10/2019
Actual
5/05/2019
Date of last data collection
Anticipated
22/12/2019
Actual
7/06/2019
Sample size
Target
20
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 292303 0
University
Name [1] 292303 0
Deakin University
Country [1] 292303 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
Melbourne Burwood Campus, 221 Burwood Highway, VIC 3125
Country
Australia
Secondary sponsor category [1] 290986 0
None
Name [1] 290986 0
n/a
Address [1] 290986 0
n/a
Country [1] 290986 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293778 0
Deakin University Human Research Ethics Guidelines
Ethics committee address [1] 293778 0
Melbourne Burwood Campus, 221 Burwood Highway, Burwood, VIC 3125
Ethics committee country [1] 293778 0
Australia
Date submitted for ethics approval [1] 293778 0
15/01/2018
Approval date [1] 293778 0
29/01/2018
Ethics approval number [1] 293778 0

Summary
Brief summary
ASD is characterized by: i) social deficits and ii) repetitive and restrictive patterns of behaviours and interests (RRPBIs). RRPBIs has been less researched in the scientific literature than the more salient social deficits. However, RRPBIs lead to severe impairments in cognitive flexibility skills and daily functioning. Some of the characteristics of RRPBIs include inflexible routines (e.g., not eating food that is coloured green or going outside without a favourite pair of shoes), rigid adherence to rules, resistance to change, obsessions, and difficulties adapting to new social contexts. Additionally, people with ASD showing highly rigid behaviour and thinking may persevere obsessively in a conversation topic or get very upset when their routine changes (e.g., always going to the shops the same way). These problems are intimately related to failures of emotional self-regulation, which is used to control one's behaviour, particularly when experiencing intrusive thoughts and negative emotions, and is thus essential for adaptive social interactions and daily functioning. Cognitive inflexibility and impairments in emotional self-regulation may also lead to increased levels of parental stress and negative parenting styles that decreases quality of life for both children and parents.
Inflexible and perseverative behaviours can be measured using reversal learning paradigms whereas emotional self-regulation is usually measured using cognitive reappraisal tasks. These two processes are widely distributed across the brain. Recent cognitive neuroscience research has revealed that a single brain region within the frontal lobe, the ventrolateral prefrontal cortex (vlPFC) is primarily responsible for monitoring cognitive flexibility and controlling negative emotions, thoughts, and behaviours. Moreover, recent evidence from brain scanning techniques demonstrate abnormal activity within the vlPFC in ASD. Thus, the vlPFC is a clear target for neurobiological treatment of cognitive inflexibility and impairments in emotional self-regulation in ASD. 20 participants between 16–30 years with ASD will be recruited. Participants will undergo 1 day of pre-testing; 4 consecutive days of 20 minutes anodal or sham HD-tDCS stimulation (depending on order of administration); half-a-day of post-testing the day after the last stimulation session; a 2-week follow-up assessment. After a 4-week washout period, participants repeat the prior process in the opposite treatment condition they commenced with (anodal or sham HD-tDCS). The is a randomised, double-blind, crossover trial that aims to (a) investigate the safety of using HD-tDCS within ASD and (b) to investigate the efficacy of using HD-tDCS to reduce impairments in cognitive flexibility and emotional self-regulation skills among individuals with ASD. We will examine a range of clinical, neuropsychological and neurophysiological features. Participants’ experience of HD-tDCS, including any side effects will be collected.
Trial website
n/a
Trial related presentations / publications
n/a
Public notes

Contacts
Principal investigator
Name 60946 0
Dr NATALIA ALBEIN-URIOS
Address 60946 0
Deakin University

Melbourne Burwood Campus, 221 Burwood Highway, VIC 3125
Country 60946 0
Australia
Phone 60946 0
+61 92517813
Fax 60946 0
Email 60946 0
[email protected]
Contact person for public queries
Name 60947 0
Dr NATALIA ALBEIN-URIOS
Address 60947 0
Deakin University

Melbourne Burwood Campus, 221 Burwood Highway, VIC 3125
Country 60947 0
Australia
Phone 60947 0
+61 92517813
Fax 60947 0
Email 60947 0
[email protected]
Contact person for scientific queries
Name 60948 0
Dr NATALIA ALBEIN-URIOS
Address 60948 0
Deakin University

Melbourne Burwood Campus, 221 Burwood Highway, VIC 3125
Country 60948 0
Australia
Phone 60948 0
+61 92517813
Fax 60948 0
Email 60948 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
The clinical trial data from the participants will be confidential.


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.