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
ACTRN12611000731998
Ethics application status
Approved
Date submitted
6/04/2010
Date registered
13/07/2011
Date last updated
9/06/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Transcranial Direct Current Stimulation (tDCS) treatment for auditory hallucinations and thinking problems in schizophrenia
Scientific title
A randomized controlled trial of transcranial Direct Current Stimulation to reduce auditory hallucinations and enhance cognitive function in schizophrenia
Secondary ID [1] 1583 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 257096 0
Condition category
Condition code
Mental Health 257251 257251 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
transcranial Direct Current Stimulation (tDCS)
TDCS involves the application of a mild constant electrical current of 2 mA to predefined brain regions of interest through placement of electrodes on the scalp surface. The current induces intracerebral current flow. This current flow then either increases or decreases the neuronal excitability in the specific area being stimulated based on which type of stimulation is being used: cathodal (decreases excitability), or anodal (increases excitability).
The total duration of a single session is 20 minutes. Each treatment phase will include 20 consecutive weekdays (or 4 weeks). Participants may continue for up to 12 weeks, depending on the allocation within the trial, and therapeutic responsiveness.
Intervention code [1] 256262 0
Treatment: Devices
Comparator / control treatment
The study will involve 2 phases. In the first phase of this study all 40 participants will be randomly assigned to 4 weeks of either active asymmetrical tDCS or sham treatment using a double-blind design, such that half of the participants will receive active and half of the participants will receive sham treatment. During the second phase of the study all participants in the active arm will be assigned to another 4 weeks of either asymmetrical tDCS or bilateral tDCS on the basis of treatment response: those responding to asymmetrical will continue with asymmetrical tDCS, while those not responding to asymmetrical tDCS will begin bilateral tDCS – see below, using an “open label” un-blinded design. Following 4 weeks of sham treatment, participants in this arm will enter an arm of 4 weeks of active tDCS, randomized to either asymmetrical or bilateral tDCS.

The active and sham treatments will have a duration of 20 minutes and will be conducted on consecutive weekdays. In the case of the asymmetrical tDCS set-up, the location of the cathodal electrode will be the temporo-parietal junction (TPJ) of the left hemisphere, and the anodal electrode will be placed over the right dorsolateral prefrontal cortex (DLPFC). Stimulation will be conducted at 2mAmp intensity. In the case of bilateral tDCS, 4 sites wil be stimulated at 1 mAmp intensity: cathodal electrodes will be positioned over the bilateral TPJ and anodal electrodes will be positioned over the bilateral DLPFC.

Assessments of symptom severity, cognitive function, general daily functioning, as well as Brain Derived Neurotrophic Factor (BDNF) levels in the blood, and brain activity measured by means of Magnetic Resonance Imaging (MRI) will be conducted at baseline and following each 4 week treatment period of the study.

The first phase will use a double-blind design in which the tDCS administrator will be aware of the active or sham condition, but both the patient and the researchers administering the clinical and cognitive assessments will not be aware of the treatment condition.
Sham tDCS will consist of the same set-up and electrode positions as the actual tDCS treatment. However, the stimulator will be turned on for just 30 seconds, during which time current intensity will be ramped up, an back down. This will provide a similar sensation to the actual tDCS, decreasing the likelihood that participants will notice the difference between real and sham tDCS.
Control group
Placebo

Outcomes
Primary outcome [1] 258154 0
Severity of positive and negative symptoms in schizophrenia measured by means of the Positive and Negative Syndrome Scale (PANSS), Psychotic Symptoms Rating Scale (PSYRATS), and the Hallucinations Rating Scale (AHRS).
Timepoint [1] 258154 0
Baseline
After each 4 week treatment phase
Secondary outcome [1] 263790 0
Magnetic resonance imaging (MRI) consisting of a a high resolution structural MRI scan, an MR spectroscopy scan using a MEGA-PRESS technique to measure concentrations of glutamate/glutamine and gamma-aminobutyric acid (GABA) in the frontal lobe, and a resting state functional MRI will provide data for connectivity analyses. These brain measures will be correlated with the primary clinical outcome measures.
Timepoint [1] 263790 0
Baseline
After each 4 week treatment phase
Secondary outcome [2] 263791 0
Brain Derived Neurotrophic Factor (BDNF) genetic analysis and blood levels
Timepoint [2] 263791 0
Baseline
After each 4 week treatment phase
Secondary outcome [3] 335783 0
Cognitive function as measured by the MATRICS battery of cognitive tests (especially tests of working memory).
Timepoint [3] 335783 0
Baseline and week 4

Eligibility
Key inclusion criteria
Patients will be included if they (1) are competent to give informed consent, as determined by the referring physician or psychiatrist, (2) have persistent symptoms despite treatment with antipsychotic medication for at least 12 months, and (3) are between 18 and 50 years of age.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded if (1) they are receiving carbamazepine since it may interfere with the effects of anodal tDCS, (2) have a history of substance abuse or dependence within the past year, (3) have a concomitant neurological disorder, or (4) they are pregnant. Patients will continue their regular medication regime for the duration of the tDCS treatment trial.

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)
Allocation concealment will be attained by means of sequentially numbered opaque, sealed envelopes (SNOSE)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization by using a randomization table created by a computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Factorial
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Other reasons/comments
Other reasons
Recruitment difficulties and 5 year limitation of Ethics approval reached.
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 in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 256762 0
Self funded/Unfunded
Name [1] 256762 0
Address [1] 256762 0
Country [1] 256762 0
Australia
Funding source category [2] 256763 0
Charities/Societies/Foundations
Name [2] 256763 0
National Alliance for Research on Schizophrenia and Depression (NARSAD)
Address [2] 256763 0
60 Cutter Mill Road, Suite 404
Great Neck, New York 11021
Country [2] 256763 0
United States of America
Primary sponsor type
University
Name
University of New South Wales
Address
The University of New South Wales
SYDNEY
NSW 2052
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 256044 0
None
Name [1] 256044 0
Address [1] 256044 0
Country [1] 256044 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258788 0
University of New South Wales, Human Research Ethics Committee
Ethics committee address [1] 258788 0
Ethics Secretariat
UNSW Research Services
Rupert Myers Building, Level 3
The University of New South Wales NSW 2052
Ethics committee country [1] 258788 0
Australia
Date submitted for ethics approval [1] 258788 0
06/04/2010
Approval date [1] 258788 0
07/06/2010
Ethics approval number [1] 258788 0
UNSW HREC 10102

Summary
Brief summary
The objective of this study is to assess to what extent cathodal transcranial Direct Current Stimulation (tDCS) of the temporal cortex, in conjunction with anodal tDCS of the prefrontal cortex, may reduce auditory hallucinations, and induce improvements in cognition, and negative symptoms in people with schizophrenia who are concurrently maintained on antipsychotic treatment. The central hypothesis is that cognitive deficits and negative symptoms, having been linked to prefrontal cortex dysfunction, will be reduced by anodal stimulation of the prefrontal cortex via facilitation of neural function, and that cathodal stimulation of the temporal cortex will reduce auditory hallucinations through disruption of pathological over-activity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31020 0
A/Prof Thomas Weickert
Address 31020 0
Neuroscience Research Australia (NeuRA)
138 Barker Street
Randwick NSW 2031
Country 31020 0
Australia
Phone 31020 0
+61 2 9399 1730
Fax 31020 0
Email 31020 0
t.weickert@unsw.edu.au
Contact person for public queries
Name 14267 0
A/Prof Thomas Weickert
Address 14267 0
Neuroscience Research Australia (NeuRa)
Hospital Road
Randwick, NSW, 2031
Country 14267 0
Australia
Phone 14267 0
+61 2 9399 1730
Fax 14267 0
Email 14267 0
t.weickert@unsw.edu.au
Contact person for scientific queries
Name 5195 0
A/Prof Dr. Thomas Weickert
Address 5195 0
Neuroscience Research Australia (NeuRa)
Hospital Road
Randwick, NSW, 2031
Country 5195 0
Australia
Phone 5195 0
+61 2 9399 1730
Fax 5195 0
+61 2 9399 1034
Email 5195 0
t.weickert@neura.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary