Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001728426
Ethics application status
Approved
Date submitted
9/12/2016
Date registered
16/12/2016
Date last updated
15/02/2021
Date data sharing statement initially provided
6/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical trial of repetitive transcranial magnetic stimulation (rTMS) for improving social relating in adolescents and young adults with autism spectrum disorder (ASD)
Scientific title
A clinical trial of theta burst stimulation (TBS) to enhance social relating in autism spectrum disorder
Secondary ID [1] 290722 0
Nil
Universal Trial Number (UTN)
U1111-1190-7248
Trial acronym
TBS-ASD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism spectrum disorder (ASD) 301297 0
Condition category
Condition code
Mental Health 301047 301047 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
iTBS is a form of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive brain stimulation technique. It involves the introduction of weak electrical current in the brain, which is achieved by delivering powerful but brief magnetic pulses to the scalp with a plastic-coated metallic coil.

The intervention will be delivered by a nurse who is highly experienced in the application of rTMS (minimum 2 years’ experience). iTBS will be administered at the Epworth Centre for Innovation in Mental Health (ECIMH), Toorak Road, Camberwell.

Each of the two arms of rTMS will be administered each consecutive weekday for a four-week period (e.g., 20 treatments in total for each of the two treatment arms, which will be six-months apart).

One arm involves stimulation of right temporoparietal junction (rTPJ), while the other treatment arm involves stimulation of bilateral dorsomedial prefrontal cortex (dmPFC). The site of stimulation (i.e., where the coil will be positioned) will be determined by co-registering the participant’s head to their structural magnetic resonance imaging (MRI) brain scan, and determining the scalp positions that sit over the target brain regions (rTPJ and dmPFC).

Each iTBS treatment will last for 3 minutes and 10 seconds. Including setup time, each iTBS treatment is expected to take approximately 10 minutes.

TBS will be delivered at an intensity equivalent to 70% of the participant’s “resting motor threshold” (RMT), which is the minimum stimulator intensity required to produce a discernable hand-muscle response following a single TMS pulse delivered to the primary motor cortex.

In terms of stimulation frequency, iTBS involves the administration of 3 TMS pulses at 50Hz, repeated 5 times per second, for 2 seconds, followed by an 8 second rest. This is repeated until a total of 600 pulses have been delivered.

Treating nurses will use a standardised treatment form to monitor adherence (e.g., number of sessions attended, percentage of protocol delivered).
Intervention code [1] 296621 0
Treatment: Devices
Comparator / control treatment
The comparator treatment will be iTBS to bilateral dorsomedial prefrontal cortex (dmPFC). This is an active control.

iTBS to dmPFC will be administered for 3 minutes and 10 seconds each consecutive weekday for a four-week period (20 treatments in total).
Control group
Active

Outcomes
Primary outcome [1] 300470 0
Change in social relating as measured by the Social Responsiveness Scale - 2nd Edition (SRS-2)
Timepoint [1] 300470 0
Baseline; Post-treatment; 1-month post-treatment; 3-months post-treatment; 6-months post-treatment.
Secondary outcome [1] 330037 0
Change in autistic traits, determined by the Autism Spectrum Quotient (AQ)
Timepoint [1] 330037 0
Baseline; Post-treatment; 1-month post-treatment; 3-months post-treatment; 6-months post-treatment.
Secondary outcome [2] 330038 0
Change in "theory of mind" performance on the Yoni task (computerised experimental task)
Timepoint [2] 330038 0
Post-treatment; 1-month post-treatment; 3-months post-treatment; 6-months post-treatment.
Secondary outcome [3] 330039 0
Change in brain activation with "social brain" regions (as determined using functional magnetic resonance imaging [fMRI])
Timepoint [3] 330039 0
Baseline; Post-treatment
Secondary outcome [4] 330040 0
Change in autistic symptomatology on the Autism Diagnostic Rating Scale (ADOS)
Timepoint [4] 330040 0
Baseline; 6-months post-treatment
Secondary outcome [5] 330041 0
Change in cognitive function on the NIH Cognition Toolbox
Timepoint [5] 330041 0
Baseline; End of each iTBS treatment week; 1-month post-treatment; 3-months post-treatment; 6-months post-treatment
Secondary outcome [6] 330042 0
Non-invasive brain stimulation Post-stimulation Survey, version 4 (formal safety/side-effect measure; possible side-effects include mild headache and transient discomfort at the site of stimulation during stimulation)
Timepoint [6] 330042 0
End of each iTBS treatment week

Eligibility
Key inclusion criteria
- DSM-5 diagnosis of autism spectrum disorder (ASD), OR DSM-IV/DSM-IV-TR diagnosis of autistic disorder or Asperger's disorder
- Formal IQ assessment indicating FSIQ 55 or higher
- Social Responsiveness Scale (SRS) score in the clinical range (60 or above)
Minimum age
14 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
STUDY EXCLUSION CRITERIA:

- Seizure history
- First degree relative with seizure disorder
- History of serious head injury
- Presence of ferromagnetic metal in the head outside the mouth
- Presence of implanted medical device
- Pregnant or lactating
- Current substance use disorder
- Neurological or psychiatric disorder other than common comorbid disorders (specifically, ADHD, depression, anxiety, OCD)
- Professional driver or machine operator

REQUIREMENTS FOR INDIVIDUAL iTBS TREATMENT SESSIONS:

- Recreational drugs or alcohol within past 24 hours
- Change in medication regime within past 4 weeks
- Typical sleep pattern (within 20%) previous 24 hours

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)
Sealed opaque envelopes
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 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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/01/2017
Actual
15/05/2017
Date of last participant enrolment
Anticipated
17/02/2020
Actual
17/02/2020
Date of last data collection
Anticipated
23/12/2020
Actual
2/12/2020
Sample size
Target
20
Accrual to date
Final
17
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295152 0
Charities/Societies/Foundations
Name [1] 295152 0
Brain and Behavior Research Foundation
Country [1] 295152 0
United States of America
Primary sponsor type
University
Name
Deakin University
Address
221 Burwood Hwy
Burwood, VIC 3125
Country
Australia
Secondary sponsor category [1] 293972 0
None
Name [1] 293972 0
Address [1] 293972 0
Country [1] 293972 0
Other collaborator category [1] 279367 0
Hospital
Name [1] 279367 0
The Alfred
Address [1] 279367 0
55 Commercial Rd
Melbourne, VIC 3004
Country [1] 279367 0
Australia
Other collaborator category [2] 279368 0
University
Name [2] 279368 0
Monash University
Address [2] 279368 0
Wellington Rd & Blackburn Rd
Clayton, VIC 3800
Country [2] 279368 0
Australia
Other collaborator category [3] 281199 0
Hospital
Name [3] 281199 0
The Epworth
Address [3] 281199 0
888 Toorak Rd,
Camberwell VIC 3124
Country [3] 281199 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296501 0
Alfred Health HREC
Ethics committee address [1] 296501 0
Ethics committee country [1] 296501 0
Australia
Date submitted for ethics approval [1] 296501 0
31/08/2016
Approval date [1] 296501 0
03/10/2016
Ethics approval number [1] 296501 0
432/16
Ethics committee name [2] 296502 0
Deakin University HREC
Ethics committee address [2] 296502 0
Ethics committee country [2] 296502 0
Australia
Date submitted for ethics approval [2] 296502 0
04/10/2016
Approval date [2] 296502 0
06/12/2016
Ethics approval number [2] 296502 0
2016-325
Ethics committee name [3] 296503 0
Monash University HREC
Ethics committee address [3] 296503 0
Ethics committee country [3] 296503 0
Australia
Date submitted for ethics approval [3] 296503 0
08/12/2016
Approval date [3] 296503 0
08/12/2016
Ethics approval number [3] 296503 0
2016-7751
Ethics committee name [4] 305390 0
Epworth HealthCare Research Development and Governance Unit
Ethics committee address [4] 305390 0
Ethics committee country [4] 305390 0
Australia
Date submitted for ethics approval [4] 305390 0
03/10/2019
Approval date [4] 305390 0
18/10/2019
Ethics approval number [4] 305390 0
EH2018-383

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1316 1316 0 0
/AnzctrAttachments/372005-432-16 Certificate of Approval.pdf (Ethics approval)
Attachments [2] 1317 1317 0 0
/AnzctrAttachments/372005-2016325-161206-A-o.pdf (Ethics approval)
Attachments [3] 1318 1318 0 0
/AnzctrAttachments/372005-Project 2016-7751 Registration.pdf (Ethics approval)
Attachments [4] 1319 1319 0 0
/AnzctrAttachments/372005-FINAL TBS-ASD PICF v1.3 09.11.16 Parent or Guardian.pdf (Participant information/consent)
Attachments [5] 1320 1320 0 0
/AnzctrAttachments/372005-FINAL TBS-ASD PICF v1.3 09.11.16 Self Adult.pdf (Participant information/consent)
Attachments [6] 1321 1321 0 0
/AnzctrAttachments/372005-FINAL TBS-ASD PICF v1.4 09.11.16 3rd Party Report.pdf (Participant information/consent)
Attachments [7] 1324 1324 0 0
/AnzctrAttachments/372005-TBS in ASD Protocol v1.3 22.11.2016.pdf (Protocol)

Contacts
Principal investigator
Name 71078 0
Prof Peter Enticott
Address 71078 0
School of Psychology, Deakin University
221 Burwood Hwy
Burwood, VIC 3125
Country 71078 0
Australia
Phone 71078 0
+61 3 9244 5504
Fax 71078 0
Email 71078 0
[email protected]
Contact person for public queries
Name 71079 0
Peter Enticott
Address 71079 0
School of Psychology, Deakin University
221 Burwood Hwy
Burwood, VIC 3125
Country 71079 0
Australia
Phone 71079 0
+61 3 9244 5504
Fax 71079 0
Email 71079 0
[email protected]
Contact person for scientific queries
Name 71080 0
Peter Enticott
Address 71080 0
School of Psychology, Deakin University
221 Burwood Hwy
Burwood, VIC 3125
Country 71080 0
Australia
Phone 71080 0
+61 3 9244 5504
Fax 71080 0
Email 71080 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
We have not sought approval for IPD to be made available for this trial.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6938Study protocol  [email protected]
6939Statistical analysis plan  [email protected]
6940Informed consent form  [email protected]
6941Ethical approval  [email protected]



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.