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Trial registered on ANZCTR


Registration number
ACTRN12620000504910p
Ethics application status
Submitted, not yet approved
Date submitted
12/03/2020
Date registered
23/04/2020
Date last updated
14/10/2021
Date data sharing statement initially provided
23/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Improving cognition in Early Psychosis using Transcranial Magnetic Stimulation
Scientific title
Improving cognitive functioning in early psychosis: A modelling approach using Transcranial Magnetic Stimulation
Secondary ID [1] 300782 0
None
Universal Trial Number (UTN)
None
Trial acronym
EPYCOG
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Psychosis 316644 0
Schizophrenia 316645 0
Personality Disorders 316897 0
Condition category
Condition code
Mental Health 314876 314876 0 0
Schizophrenia
Mental Health 314985 314985 0 0
Psychosis and personality disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All interventions/exposure are administered face-to-face with the participant.

Prior to TMS the participant will have a functional and structural MRI brain scan. The MRI will be overseen by the lead PI, who is a psychiatrist.

Assessment of motor cortex excitability using electromyography electrodes on the skin overlying surface muscles of the arm; single pulses of TMS are given to the motor cortex of the participant to induce contraction of muscle in the arm with a motor potential of greater than 200 µV recorded on electromyography. The stimulation intensity required to evoke contraction at the motor potential of greater than 200 µV on at least 3 out of 5 trials is noted. The stimulation intensity to be used for the intervention will be set to 80 percent of the dose necessary to induce muscle contraction at motor potential of greater than 200 µV i.e. the active motor threshold. The assessment of motor cortex excitability will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA.

Active Intervention: A standard intermittent theta burst stimulation (iTBS) protocol will be used to induce local changes in cortical activity at the left and right dorsolateral prefrontal cortex (in that order), interleaved by 60 minutes between left and right target sites. The iTBS uses a stimulation pattern in which 3 pulses of stimulation are given at 50 Hz, repeated at 5 Hz for 2 secs, with a total of 600 total train pulses at 80 percent of active motor threshold. This dose will be delivered to each site in a single session (interleaved 60 minutes between doses) on one day only. During the interleaved 60 minute period the participant will be required to remain in a quiet room. A trained RA will administer questionnaires (e.g. adverse event log) and take the participant through the tasks that will be undertaken in the MRI. The active intervention will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA.

Placebo Intervention: Placebo stimulation will be administered with a specific coil that is made by the same manufacturer. This coil mimics the noise and effects on the scalp muscles of the real TMS but does not affect the neural activity of the targeted area.
The placebo intervention will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA.

Orientation of brain region target for active and placebo intervention is performed using neuro-navigation software and hardware called visor2 (https://www.ant-neuro.com/products/visor2). The visor 2 system uses the participant’s structural MRI scan to personalise the targeting of TMS to the individual’s unique brain anatomy. The orientation of brain region target for active and placebo intervention will be performed the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA.

The participant will undergo two post-intervention assessments. The participant will complete an adverse event log during (within 60 mins of first TMS) and after TMS dosing (within 60 mins of second TMS and up to 1 week after second TMS). The participant will complete an MRI brain scan within 60 minutes after second TMS dosing so as to measure the functional brain changes that occur as a result of intervention. Both these post-intervention assessments will be overseen by the lead PI, who is a psychiatrist.
Intervention code [1] 317103 0
Treatment: Devices
Comparator / control treatment
The control arm participants will undergo “sham” TMS using a “dummy” coil. The dummy coil has the same programmed dose and duration as the active intervention; intermittent theta burst stimulation with a stimulation pattern in which 3 pulses of stimulation are given at 50 Hz, repeated at 5 Hz for 2 secs, with a total of 600 total train pulses at 80 percent of active motor threshold (40 seconds total). However, the dummy coil contains a buffer that retards the magnetic field so as to only affect the scalp muscles and not pass through the skull bone. The administration occurs face-to-face.
Control group
Placebo

Outcomes
Primary outcome [1] 323209 0
Functional connectivity change from pre-TMS to post-TMS measured using an MRI brain scan.
Timepoint [1] 323209 0
Within 60 minutes of TMS dose
Secondary outcome [1] 381184 0
Behavioural performance (accuracy in trials) in the Multi-source Interference Task used in the MRI brain scan.
Timepoint [1] 381184 0
within 60 minutes of TMS dose.
Secondary outcome [2] 381185 0
Safety measured using attrition rate. Attrition rate will be assessed as people who withdraw from the study and recorded in the case report forms.
Timepoint [2] 381185 0
up to 1 week after TMS dose.
Secondary outcome [3] 381443 0
Behavioral performance (reaction time in trials) in the Multi- sourced interference task used in the MRI brain scan. Reaction time is assessed by a software package called “Presentation”.
Timepoint [3] 381443 0
within 60 minutes of TMS dose.
Secondary outcome [4] 381444 0
Tolerability measured using attrition rate (participant drop-out). Attrition rate will be assessed as people who withdraw from the study and recorded in the case report forms.
Timepoint [4] 381444 0
up to one week after TMS dose
Secondary outcome [5] 381707 0
Safety measured using (participant drop-out) and adverse event logs. Known adverse events include, seizure, fainting, dizziness, nausea and vomiting, headache, muscle ache, muscle spasm, sensory problems, difficulties understanding speech or speaking, lack of co-ordination, slowness or impairment of thought.

These adverse events will be assessed by study-specific questionnaire, participant self-report and clinical examination.
Timepoint [5] 381707 0
up to 1 week post TMS dose
Secondary outcome [6] 381708 0
Tolerability measured using and adverse event logs. Known adverse events include, seizure, fainting, dizziness, nausea and vomiting, headache, muscle ache, muscle spasm, sensory problems, difficulties understanding speech or speaking, lack of co-ordination, slowness or impairment of thought.

These adverse events will be assessed by study-specific questionnaire, participant self-report and clinical examination.
Timepoint [6] 381708 0
up to one week post TMS dose

Eligibility
Key inclusion criteria
1. Safe to undertake MRI
2. Safe to undertake TMS
3. Broadly defined psychotic disorder according to DSM-V criteria
4. Has capacity to give informed consent
Minimum age
18 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy
2. History of seizure disorder
3. History of neurological disorder
4. History of Traumatic Brain Injury

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)
Central randomization by computer.
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


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
35 participants, (25 active intervention 10 placebo intervention). Neuroimaging results from previous TMS studies have indicated that 25 participants is an adequate sample size. Seed-to-voxel correlation analyses will be used to examine patterns of functional connectivity between target sites with voxels in the rest of the brain. These will be calculated pre-TMS and post-TMS using paired-sample t-tests with the resting-state and task fMRI data to analyse changes in functional connectivity.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Did not proceed
Date of first participant enrolment
Anticipated
3/08/2020
Actual
Date of last participant enrolment
Anticipated
17/01/2022
Actual
Date of last data collection
Anticipated
24/01/2022
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 29633 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 305241 0
Other Collaborative groups
Name [1] 305241 0
Collaborative Research Grant, QIMR Berghofer Medical Research Institute and Metro-North Hospital and Health Service
Country [1] 305241 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
QIMR Berghofer Medical Research Institute, 300 Herston Rd Herston, Queensland 4006
Country
Australia
Secondary sponsor category [1] 305597 0
None
Name [1] 305597 0
Address [1] 305597 0
Country [1] 305597 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305583 0
QIMR Berghofer Human Research Ethics Committee
Ethics committee address [1] 305583 0
Ethics committee country [1] 305583 0
Australia
Date submitted for ethics approval [1] 305583 0
18/02/2020
Approval date [1] 305583 0
Ethics approval number [1] 305583 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100858 0
Dr Bjorn Burgher
Address 100858 0
QIMR Berghofer Medical Research Institute
300 Herston Rd Herston, Queensland, 4006
Country 100858 0
Australia
Phone 100858 0
+61 7 3362 0369
Fax 100858 0
Email 100858 0
Bjorn.burgher@qimrberghofer.edu.au
Contact person for public queries
Name 100859 0
Bjorn Burgher
Address 100859 0
QIMR Berghofer Medical Research Institute
300 Herston Rd Herston, Queensland, 4006
Country 100859 0
Australia
Phone 100859 0
+61 7 3362 0369
Fax 100859 0
Email 100859 0
Bjorn.burgher@qimrberghofer.edu.au
Contact person for scientific queries
Name 100860 0
Bjorn Burgher
Address 100860 0
QIMR Berghofer Medical Research Institute
300 Herston Rd Herston, Queensland, 4006
Country 100860 0
Australia
Phone 100860 0
+61733620369
Fax 100860 0
Email 100860 0
Bjorn.burgher@qimrberghofer.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
MRI brain data, clinical and demographic data of all participants
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Any purpose
How or where can data be obtained?
access subject to approvals by Principal Investigator (bjorn.burgher@qimrberghofer.edu.au)


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.