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Trial registered on ANZCTR


Registration number
ACTRN12618001705279
Ethics application status
Approved
Date submitted
26/09/2018
Date registered
16/10/2018
Date last updated
2/05/2022
Date data sharing statement initially provided
11/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Developing Alternative Treatments for Young People with Depression: A study of transcranial alternating current stimulation (tACS).
Scientific title
Developing Alternative Treatments for Young People with Depression: A study of transcranial alternating current stimulation (tACS).
Secondary ID [1] 296090 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
You-tACS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early stage Depression 309665 0
Condition category
Condition code
Mental Health 308466 308466 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
tACS treatment frequency will be determined during an EEG recording (see EEG assessment section below for details on EEG recording equipment). During the EEG recording, the N-back working memory task will be administered to participants to elicit theta oscillations, and the Sternberg working memory task will be administered to elicit alpha oscillations. Stimulation frequency will then be set to each individual’s theta and alpha frequency measurements, depending on the treatment allocated. The current of tACS delivered 48,000 cycles (i.e. 20 mins) with no DC current offset. The current ramps gently over a period of e.g. 5-10 seconds to the desired peak for patient comfort. The stimulator fade in and fade out was specified to 100 cycles at the beginning and end of stimulation. A pair of 5x5cm electrodes placed within saline soaked sponges and a purpose-built battery-driven constant stimulator will deliver the current. The electrodes will be placed over the left pre-frontal cortex on F5 and, over the right pre-frontal cortex on F6, located using the 10-20 EEG position. This electrode montage has been modelled to show a reasonably widespread current flow through fronto-central cortical and frontal subcortical regions.

tACS treatment course: The tACS course is a 4 week program that has two phases. A ‘lead in/out’ phase that happens at week 1 and week 4 and an intensive phase that happens during week 2 and week 3.
• Week 1 and week 4 – one 20 minute session of tACS per day for 5 days a week (Monday to Friday)
• Week 2 and week 3 – two 20 minute sessions of tACS per day with at least 4 hours break between sessions, for 5 days a week (Monday to Friday).
Intervention code [1] 312431 0
Treatment: Devices
Comparator / control treatment
Sham protocol: Sham stimulation is achieved by applying a period of 2 minutes of tACS at 13 Hz (i.e. a low beta frequency) with a 10 second ramp on and 10 second ramp off to provide the participant an experience of stimulation. The switching off of the stimulation pre-programmed within the software of the device. The participant will just turn the device on for 20 minutes without any indication of the type of stimulation. There is no evidence that the brief 120 second period of stimulation produces lasting biological effects.
Control group
Placebo

Outcomes
Primary outcome [1] 307475 0
Changes in severity of depressive symptoms as measured by change in Montgomery-Asberg Depression Rating Scale (MADRS) scores.
Timepoint [1] 307475 0
Baseline, 4 weeks (end-point)
Primary outcome [2] 307569 0
Changes in severity of depressive symptoms as measured by change in Beck Depression Inventory (BDI) scores.
Timepoint [2] 307569 0
Baseline, 4 weeks (end-point)
Primary outcome [3] 307570 0
Changes in severity of depressive symptoms as measured by change in Five Facet Mindfulness Questionnaire (FFMQ) scores.
Timepoint [3] 307570 0
Baseline, 4 weeks (end-point)
Secondary outcome [1] 352002 0
Whether changes in depression severity are sustained over a three month period, as measured by change in MADRDS scores.
Timepoint [1] 352002 0
Baseline, mid-point, end-point and 3 months post end-point
Secondary outcome [2] 352076 0
Whether changes in depression severity are sustained over a three month period, as measured by change in BDI scores.
Timepoint [2] 352076 0
Baseline, mid-point, end-point and 3 months post end-point
Secondary outcome [3] 352077 0
Whether changes in depression severity are sustained over a three month period, as measured by change in FFMQ scores.
Timepoint [3] 352077 0
Baseline, mid-point, end-point and 3 months post end-point
Secondary outcome [4] 352078 0
The tolerability of active compared with sham stimulation as measured by scores on the usability questionnaire and side-effects questionnaire designed specifically for this study.
Timepoint [4] 352078 0
2 weeks (mid-point) and 4 weeks (end-point)
Secondary outcome [5] 352079 0
Drop-out rates of active theta and alpha tACS compared with sham stimulation as measured by scores on adherence data recorded by BrightStim device.
Timepoint [5] 352079 0
Baseline, end-point
Secondary outcome [6] 352084 0
Whether endogenous theta oscillations can be entrained with tACS treatment measured by change in EEG recording of theta frequency during N-Back task.
Timepoint [6] 352084 0
Baseline, end-point, 3 months post end-point
Secondary outcome [7] 352210 0
Whether endogenous alpha oscillations can be entrained with tACS treatment measured by change in EEG recording of alpha frequency during Sternberg task.
Timepoint [7] 352210 0
Baseline, end-point, 3 months post end-point
Secondary outcome [8] 352213 0
Whether there are working memory improvements with tACS treatment as measured by changes in N-back task scores.
Timepoint [8] 352213 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [9] 352214 0
Whether there are cognition improvements with tACS treatment as measured by change in Sternberg task scores.
Timepoint [9] 352214 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [10] 352215 0
Whether there are processing speed and attention improvements with tACS treatment as measured by change in Digit Span task scores.
Timepoint [10] 352215 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [11] 352216 0
Whether there are psychomotor speed and set-shifting improvements with tACS treatment as measured by change in Trails task scores.
Timepoint [11] 352216 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [12] 352217 0
Whether there are verbal learning and memory improvements with tACS treatment as measured by change in Rey Auditory Verbal Learning Test scores.
Timepoint [12] 352217 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [13] 352218 0
Whether there are visuospatial learning and memory improvements with tACS treatment as measured by change in Brief Visuospatial Memory Test scores.
Timepoint [13] 352218 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [14] 352219 0
Whether there are attention and cognitive flexibility improvements with tACS treatment as measured by change in STROOP scores.
Timepoint [14] 352219 0
Baseline, end-point, 3 months post end-point.
Secondary outcome [15] 352220 0
Whether there are cognition improvements with tACS treatment as measured by change in Wechsler Test of Adult Reading scores.
Timepoint [15] 352220 0
Baseline, end-point, 3 months post end-point.

Eligibility
Key inclusion criteria
-Diagnosis of major depressive episode (MDE), in accordance with the Mini International Neuropsychiatric Interview
- Individuals between 16 to 30 years of age
- Depression severity quantified using the Montgomery-Asberg Depression Rating Scale (MADRS) cut-off scores (mild: 7-19; moderate: 20-34; severe: >34)
- No more than 2 previously received adequate trials of antidepressant treatment
- Demonstrated capacity to give informed consent
Minimum age
16 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Inability to give informed consent
-DSM V diagnoses of a psychotic disorder or current substance-use disorders;
-Developmental disorders (including autism);
-History of sustained head injury;
-Other neurological illness;
-Intellectual disability;
-Major medical illness impacting brain function
-Pregnancy

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)
This is a double-blind study. Neither the participant nor the researcher conducting the sessions will know what type of stimulation the participant is receiving during each session. An external researcher, who will be unblinded and off site, will provide a unique code to be entered into the tACS stimulator, which will determine the stimulation condition and settings, thus allowing the second researcher to remain blinded.
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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Up to 144 (48 in each treatment arm)
To assess the primary hypothesis, the MADRS data will be analysed using intention-to-treat mixed-effects, general linear mixed modelling. Post-hoc analyses will be conducted to interrogate any significant interaction effects of group (theta, alpha and sham) by time (baseline, mid-point change, end-point change) comparing consecutive changes from baseline to mid-point, end-point and 3 months after tACS.
Similarly, to assess changes in cognition and theta and alpha over time, the data will be analysed using intention-to-treat mixed-effects, general linear mixed modelling. Post-hoc analyses will be conducted to interrogate any significant interaction effects of group (theta, alpha and sham) by time (baseline, end-point change and 3 month change) comparing consecutive changes from baseline to end-point and 3 months after tACS.
Up to two interim analyses of the primary outcome variable are planned in addition to the final analysis and decisions to stop the trial early for efficacy or for futility will be based on a generalized Dunnett test for multi-arm multi-stage trials.

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
13/03/2019
Actual
12/06/2019
Date of last participant enrolment
Anticipated
1/11/2021
Actual
17/02/2022
Date of last data collection
Anticipated
28/02/2022
Actual
28/04/2022
Sample size
Target
144
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11942 0
Epworth Rehabilitation Camberwell - Camberwell
Recruitment postcode(s) [1] 24086 0
3124 - Camberwell

Funding & Sponsors
Funding source category [1] 300678 0
Charities/Societies/Foundations
Name [1] 300678 0
Perpetual Foundation IMPACT Philanthropy Program
Country [1] 300678 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Wellington Rd, Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 300233 0
None
Name [1] 300233 0
Address [1] 300233 0
Country [1] 300233 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301460 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 301460 0
Ethics committee country [1] 301460 0
Australia
Date submitted for ethics approval [1] 301460 0
22/08/2018
Approval date [1] 301460 0
14/11/2018
Ethics approval number [1] 301460 0

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

Contacts
Principal investigator
Name 87082 0
Prof Paul Fitzgerald
Address 87082 0
Epworth Centre for Innovation in Mental Health
Ground Floor
888 Toorak Rd
Camberwell 3124
VIC
Country 87082 0
Australia
Phone 87082 0
+61 3 9805 4287
Fax 87082 0
Email 87082 0
[email protected]
Contact person for public queries
Name 87083 0
Kate Gunningham
Address 87083 0
Epworth Centre for Innovation in Mental Health
Ground Floor
888 Toorak Rd
Camberwell 3124
VIC
Country 87083 0
Australia
Phone 87083 0
+61 3 9805 4297
Fax 87083 0
Email 87083 0
[email protected]
Contact person for scientific queries
Name 87084 0
Manreena Kaur
Address 87084 0
Epworth Centre for Innovation in Mental Health
Ground Floor
888 Toorak Rd
Camberwell 3124
VIC
Country 87084 0
Australia
Phone 87084 0
+61 3 9076 9850
Fax 87084 0
Email 87084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data set will be shared, in de-identified form only.
When will data be available (start and end dates)?
Available following publication, and no end date determined.
Available to whom?
Available on a case-by-case basis at the discretion of the Principal Investigator, dependent on the proposal and methods of those wishing to access.
Available for what types of analyses?
Dependent on the proposal and methods of those wishing to access.
How or where can data be obtained?
As yet undecided.


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.