Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612001208897
Ethics application status
Approved
Date submitted
14/11/2012
Date registered
15/11/2012
Date last updated
19/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Deep repetitive transcranial magnetic stimulation for autism spectrum disorder
Scientific title
For individuals with autism spectrum disorder, does active deep repetitive transcranial magnetic stimulation (rTMS) as compared to sham deep rTMS improve social relating?
Secondary ID [1] 281545 0
Nil
Universal Trial Number (UTN)
U1111-1137-0543
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism spectrum disorder 287811 0
Autistic disorder 287812 0
Asperger's disorder 287813 0
Pervasive developmental disorder - not otherwise specified 287814 0
Condition category
Condition code
Mental Health 288162 288162 0 0
Autistic spectrum disorders
Mental Health 288170 288170 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Active deep repetitive transcranial magnetic stimulation. This is a non-invasive means of stimulating the brain via a plastic-coated metallic coil that is placed over the scalp. Stimulation will be provided at 110% of resting motor threshold (i.e., minimum stimulation intensity required to activate the brain's motor system). There will be 18 half-hour treatments in total: every consecutive weekday for three weeks, and then three days the following week. Each session involves the administration of 60 10-second stimulation trains at 5 Hz, with a 20 second inter-train interval. This is identical for both Phas e 1 and Phase 2 of the study, except Phase 1 involves undergoing a one-hour brain imaging (PET) session before and after the treatment course. Participants will only take part in Phase 1 or Phase 2, not both. Phase 1 and Phase 2 will be run in parallel.
Intervention code [1] 286058 0
Treatment: Devices
Comparator / control treatment
Placebo deep repetitive transcranial magnetic stimulation. This involves a simulated procedure in which a coil is placed over the head, no no magnetic pulses are delivered to the brain. The placebo is only used in Phase 2 of the trial; Phase 1 investigates the brain's response to deep repetitive transcranial magnetic stimulation, and is not placebo controlled.
Control group
Placebo

Outcomes
Primary outcome [1] 288363 0
Social relating as indicated by the Ritvo Autism-Aspergers Diagnostic Scale - Revised (RAADS-R)
Timepoint [1] 288363 0
Pre treatment, post treatment, one-month post treatment, three-months post treatment, six-months post treatment
Primary outcome [2] 288364 0
Social relating as measured by the Social Responsiveness Scale (SRS/SRS-A)
Timepoint [2] 288364 0
Pre treatment, post treatment, one-month post treatment, three-months post treatment, six-months post treatment
Secondary outcome [1] 299963 0
Social anxiety as measured by the Interpersonal Reactivity Index (IRI)
Timepoint [1] 299963 0
Pre treatment, post treatment, one-month post treatment, three-months post treatment, six-months post treatment
Secondary outcome [2] 299964 0
Brain metabolism with 'mentalising' network as measured by positron emission tomography (PET)
Timepoint [2] 299964 0
Pre treatment, post treatment
Secondary outcome [3] 299965 0
Accuracy and reaction time on computerised tests of mentalising
Timepoint [3] 299965 0
Pre treatment, post treatment, one-month post treatment, three-months post treatment, six-months post treatment

Eligibility
Key inclusion criteria
- Formal diagnosis of autism spectrum disorder (either autism, Asperger’s disorder, or pervasive developmental disorder not otherwise specified)
- Measured IQ of 55 or above
- Capacity to provide informed consent for self (adults) or child
- Proficiency in the use and comprehension of English (necessary not only in relation to the process of informed consent, but also the completion of English-language measures).
Minimum age
15 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of epilepsy or seizure disorder
- History of serious head injury
- Metal in the head (outside of the mouth)
- Medical/metal implants in the body
- History or neurological/psychiatric illness (other than ASD, but not those psychiatric conditions commonly present in ASD, such as depression and anxiety)
- Unstable medical condition
- Pregnant or lactating
- Professional driver or machine operator

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/03/2013
Actual
1/03/2013
Date of last participant enrolment
Anticipated
Actual
8/01/2016
Date of last data collection
Anticipated
31/12/2020
Actual
Sample size
Target
80
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 286323 0
Charities/Societies/Foundations
Name [1] 286323 0
Brain and Behaviour Research Foundation
Country [1] 286323 0
United States of America
Primary sponsor type
Individual
Name
Dr. Peter Enticott
Address
Monash Alfred Psychiatry Research Centre, Level 4, 607 St Kilda Rd, Melbourne, Victoria, 3004
Country
Australia
Secondary sponsor category [1] 285112 0
Individual
Name [1] 285112 0
Prof. Paul Fitzgerald
Address [1] 285112 0
Monash Alfred Psychiatry Research Centre, Level 4, 607 St Kilda Rd, Melbourne, Victoria, 3004
Country [1] 285112 0
Australia
Other collaborator category [1] 277174 0
Individual
Name [1] 277174 0
Prof. Abraham Zangen
Address [1] 277174 0
Brain Stimulation and Behavior lab, Biology-Psychology Program, Ben Gurion University, POB 653, Beer-Sheva, 84105
Country [1] 277174 0
Israel

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288396 0
Alfred Health
Ethics committee address [1] 288396 0
The Alfred, Commercial Rd, Melbourne, Victoria, 3004
Ethics committee country [1] 288396 0
Australia
Date submitted for ethics approval [1] 288396 0
19/11/2012
Approval date [1] 288396 0
07/01/2013
Ethics approval number [1] 288396 0
533-12
Ethics committee name [2] 288397 0
Monash University
Ethics committee address [2] 288397 0
Monash Research Office, Building 3d, Monash University, Victoria, 3800
Ethics committee country [2] 288397 0
Australia
Date submitted for ethics approval [2] 288397 0
19/11/2012
Approval date [2] 288397 0
29/01/2013
Ethics approval number [2] 288397 0

Summary
Brief summary
The prevalence of autism spectrum disorder (ASD) is currently estimated at 1 in 88, but there is a distinct lack of validated biomedical treatments that target the core symptoms. Non-invasive brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS), have been established as safe and efficacious treatments for a range of psychiatric disorders, particularly depression. We conducted a pilot, placebo-controlled study of deep rTMS (a form of rTMS providing stimulation of brain structures further away from the scalp) among individuals with ASD (n = 28) that involved a conservative two-week course of stimulation, and found evidence of improved social relating among those undergoing active deep rTMS. Following on from our pilot research, this study will examine the underlying mechanism of deep rTMS, and the safety and efficacy of a stronger course of deep rTMS in ASD.

There will be two phases to this study.

Phase 1 will involve 20 individuals with ASD aged 18 or older. They will undergo positron emission tomography (PET) and clinical assessment before and after receiving 30 minutes of active deep rTMS each weekday for 3 weeks, and for 2 weekdays of the following week. This phase will help to understand the underlying brain mechanism of deep rTMS.

Phase 2 will involve 60 individuals with ASD aged 15 or older. They will receive 30 minutes of either active (n = 30) or sham (placebo) (n = 30) deep TMS each weekday for 3 weeks, and for 2 weekdays of the following week. Clinical assessments will be conducted at five points: (1) before the first treatment, (2) immediately after the last treatment, (3) 1 month after the last treatment, (4) 3 months after the last treatment, and (5) 6 months after the last treatment. These assessments will comprise self-report and parent-report (or significant other-report) questionnaires assessing ASD symptomatology and short experimental measures assessing distinct aspects of social relating (e.g., perception of other’s emotions).

Individuals must have been assessed to have an IQ of 55 or above (i.e., mild intellectual disability, average intelligence, or above average intelligence). Capacity to provide informed consent will be evaluated and monitored for all adult participants. Child participants will require parental consent to participate.

For Phase 1, it is expected that deep rTMS will enhance activity within the brain’s ‘mentalising network’ (i.e., a series of connected regions devoted to understanding others thoughts, beliefs, intentions, and feelings) and result in clinical improvements to social relating symptoms. For Phase 2, it is expected that active deep rTMS will improve social abilities in ASD, and that these will be maintained after 6 months. Should our hypotheses be supported, it will indicate the possibility of deep rTMS as a neurobiological intervention for ASD.
Trial website
www.maprc.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34954 0
Prof Paul Fitzgerald
Address 34954 0
MAPrc
Level 4, 607 St Kilda Rd
Melbourne VIC 3004
Country 34954 0
Australia
Phone 34954 0
+61 3 9076 6564
Fax 34954 0
Email 34954 0
[email protected]
Contact person for public queries
Name 18201 0
A/Prof Peter Enticott
Address 18201 0
School of Psychology, Deakin University
221 Burwood Highway
Burwood VIC 3125
Country 18201 0
Australia
Phone 18201 0
+61 3 9244 5504
Fax 18201 0
n/a
Email 18201 0
[email protected]
Contact person for scientific queries
Name 9129 0
A/Prof Peter Enticott
Address 9129 0
School of Psychology, Deakin University
221 Burwood Highway
Burwood VIC 3125
Country 9129 0
Australia
Phone 9129 0
+61 3 9244 5504
Fax 9129 0
n/a
Email 9129 0
[email protected]

No information has been provided regarding IPD availability


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.