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Trial registered on ANZCTR


Registration number
ACTRN12623000826640
Ethics application status
Approved
Date submitted
31/05/2023
Date registered
1/08/2023
Date last updated
21/07/2024
Date data sharing statement initially provided
1/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the Efficacy of Transcranial Alternating Current Stimulation in the Treatment of Obsessive-Compulsive Disorder (tACS-OCD)
Scientific title
Investigating the Efficacy of Transcranial Alternating Current Stimulation in the Treatment of Obsessive-Compulsive Disorder (tACS-OCD)
Secondary ID [1] 309229 0
None
Universal Trial Number (UTN)
Trial acronym
tACS-OCD
Linked study record
This study is a follow-up study of the pilot study registered under ACTRN12620000748910.

Health condition
Health condition(s) or problem(s) studied:
Obsessive-compulsive disorder 329387 0
Condition category
Condition code
Mental Health 326333 326333 0 0
Anxiety
Mental Health 327128 327128 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Transcranial Alternating Current (tACS) is a form of non-invasive brain stimulation that delivers a weak electrical current that alternates at a specified frequency back and forth between electrodes. The tACS device in this trial (BrightStim2) consists of a purpose-built handheld battery driven unit that delivers a current controlled voltage across an active and reference electrode. The active and reference electrodes are placed within commercially supplied saline soaked sponges. We have developed this device within our research team to produce the same effects as existing commercial devices but to be programmable in a manner that the research team can preset the conditions of use with no capacity for the patients to alter this or use the device in a manner outside of our research protocol.
To date, there have been hundreds of studies of tACS, including in people with depression, conducted internationally. There have been no issues or problems reported in these studies over and above the known side effects.

The BrightStim stimulator was used in our pilot study (ACTRN12620000748910) that assessed the efficacy of tACS in OCD. It has also been used in other experimental studies with involving patients and healthy controls, and has also been demonstrated to produce effects equivalent to those produced with a widely commercially available device in a structured assessment. No safety or other issues/problems arose in any of these studies.

Mode of action: polarisation of neurons via mild electrical current
Dosage Regime: tACS will be applied targeting the medial prefrontal cortex with a placement of electrodes at the AFz and Iz positions. Individualised alpha frequency (IAF) will be determined for all participants through a pre-treatment electroencephalography (EEG) session and stimulation will occur at this frequency. Each tACS session will last 30 minutes (continuous) with stimulation intensity of 1.5mA.

Study Design: The study will be in the form of a randomised, double-blind, sham-controlled parallel two-arm clinical trial with an open-label crossover phase offered to the sham group.
This study has been designed according to SPIRIT Guidelines and will follow reporting of results in agreement with the international CONSORT Guidelines. Treatment will occur over a six-week period in both the initial and cross over study phases. During the first three weeks, participants will receive treatment twice daily (intensive treatment phase), 5 days per week (with a break of 2 days each week). In the subsequent three weeks, they will receive treatment once daily, three days per week (consolidation phase). After this, they will be followed up for three months to evaluate whether they have achieved treatment persistent benefits. After this time, in the open label crossover phase, participants who initially received sham will receive active tACS for 6 weeks with intensive (3 weeks) and consolidation phases (3 weeks) as before. The initial active group will continue to be followed up every 3 months for 1 year post-treatment.

Administration of intervention: The first treatment of each participant will be administered under direct supervision of an experienced investigator. After training on self-administration, and once each participant has demonstrated that they can implement the stimulation independently, participants will be permitted to administer treatments at home. Additional remote supervision and support will be provided via video and telephone communication. The tACS devices are programmed to save a log of the delivered treatments, which could be accessed by the investigator to monitor adherence. Additionally, participants are requested to maintain a log of all administered treatments.
Intervention code [1] 325672 0
Treatment: Devices
Comparator / control treatment
In the sham condition, current will be delivered at an intensity of 1.5 mA in the first and last 1 minute of the 30-minute session (including a 10 s ramp-up/down) at the IAF, to emulate sensations associated with tACS administration without producing any enduring physiological effects. There is no evidence that 1 minute of tACS induces any changes in the brain. The provision of stimulation for 1 minute allows participants to experience the initial physical sensations of tACS, which typically fade after around 30 seconds, thus providing a robust sham. This is a standard method of blinding for tACS.
Control group
Placebo

Outcomes
Primary outcome [1] 334185 0
Change in clinical severity of OCD, as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS)
Timepoint [1] 334185 0
Assessed at baseline, 3-week, 6-week and 3-month follow-up appointments post-commencement of intervention
Secondary outcome [1] 419762 0
Change in event related potentials (error related negativity and N200) as measured by EEG
Timepoint [1] 419762 0
EEG recording during Flanker and Go/Nogo tasks at baseline and post-treatment (at 6 weeks post-commencement of intervention)
Secondary outcome [2] 419763 0
Change in oscillatory power in the frontotemporal regions as measured by EEG
Timepoint [2] 419763 0
Resting eyes closed EEG recordings at baseline and post-treatment (at 6 weeks post-commencement of intervention)
Secondary outcome [3] 419764 0
Change in perceived clinical severity of OCD by participants, as measured by the Obsessive-Compulsive Inventory-Revised (OCI-R)
Timepoint [3] 419764 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [4] 419765 0
Change in co-morbid depressive symptoms, as measured by the Patient Health Questionnaire-9 (PHQ-9)
Timepoint [4] 419765 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [5] 419766 0
Change in co-morbid anxiety symptoms, as measured by the Generalised Anxiety Disorder Assessment-7 (GAD-7)
Timepoint [5] 419766 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [6] 419767 0
Change in quality of life, as measured by the AQoL-8D questionnaire
Timepoint [6] 419767 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [7] 422665 0
Change in overall symptom severity by participants, as measured by PGI-S questionnaire
Timepoint [7] 422665 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [8] 422667 0
Rating of improvement in symptoms by participants, as measured by PGI-I questionnaire
Timepoint [8] 422667 0
Assessed at baseline, 3-week, 6-week and 3-, 6-, 9- and 12-month follow-up timepoints post-commencement of intervention
Secondary outcome [9] 422668 0
A custom questionnaire to assess tACS tolerability and side effects
(Examples of known/possible side effects are: scalp discomfort, headache, neck pain, tiredness, flashing lights/phosphene perception).
Timepoint [9] 422668 0
Administered post-treatment at 6 weeks post-commencement of intervention

Eligibility
Key inclusion criteria
• 18-65 years of age.
• A clinical diagnosis of OCD confirmed on a semi-structured interview (DSM-5 screening interview) in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5)
• Have not initiated new OCD treatment (pharmacological or behavioural) or changed dosage of current psychopharmacological treatment in the past 6 weeks.
• Demonstrated capacity to give informed consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Score <17 on the baseline Yale-Brown Obsessive Compulsive Scale (YBOCS)
• Currently pregnant or breastfeeding.
• Presence of metal (screws, clips) anywhere in the head, except the mouth.
• Presence of an unstable medical condition or a neurological disorder.
• Diagnosis of another personality or psychiatric disorder except depression or another anxiety disorder.
• Inability to provide informed consent.

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 to treatment group is concealed; by the research staff contacting the study investigators, after the participant is deemed eligible and has consented for the study.
Randomisation of participants into intervention first or sham first condition will occur through a computer-generated randomisation list and an investigator who has no direct contact with participants will be responsible for programming the tACS devices prior to handing them over to participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly allocated to study group using simple randomisation techniques i.e. 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
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We aim to recruit 100 participants in total (50 participants in each arm). The required sample size was calculated using the G*power statistical power analysis program. An effect size of 0.75 was chosen to be clinical meaningful based on a recent meta-analysis of brain stimulation in OCD. With an error probability (a) of 0.05 and a power (1 – ß) of 0.8, the required sample size for each group was 30, assuming the two treatment arms (active and sham) had equal sample sizes (n1 = n2). Allowing for dropouts, we set the required sample size at 50 per group. As only a subset of all participants will be used in the pre- to post-treatment EEG and ERP analyses, dropouts were ignored for this analysis. Therefore, the required sample size for this study is 60 participants in total (30 in each group).

The primary analysis will be conducted on YBOCS scores from baseline to each time point. A linear mixed effects model will be used to estimate the time-condition interaction. Independent sample t-tests and chi-squared tests will be used to examine potential baseline differences between demographic and clinical characteristics between groups for continuous and categorical variables, respectively. Linear mixed model analysis of the primary and secondary outcome variables will be computed to look for differences in group scores across study time points (baseline, week 3, week 6) with treatment types as the between-group and time as the within-subject factor. Concurrent medication use will be included in these analyses as covariate.

Data analysis of the resting EEG data will be done using the baseline and post-treatment EEG data collected from the participants at rest. Removal of artifacts and non-oscillatory (1/f) activity will be done as an EEG pre-processing step using RELAX and eBOSC methods, respectively. Power within oscillatory frequencies will be computed using Welch transform. Statistical comparison of the power spectrum will be performed using the cluster-based permutation method.

ERP analysis will be performed on the pre-processed EEG data, time-locked to the stimuli presentation/response of each task, including all electrodes and time windows (without any specific electrode or time window selection that excludes any of the data), using randomisation statistics provided by the randomisation graphical user interphase (RAGU) software. This analysis approach applies randomisation statistics to robustly test for differences in the neural response strength using the global field potential, and for differences in the distribution of neural activity using global dissimilarity maps. This approach uses all electrodes and timepoints in its analysis while still robustly controlling for multiple comparisons using variations on traditional randomisation statistical approaches (the global duration statistic and global count statistic). The investigators involved in the study are experts at the analysis techniques proposed for use in this study, having published multiple studies implementing and also contributing to the development of these techniques.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/08/2023
Actual
1/03/2024
Date of last participant enrolment
Anticipated
11/08/2025
Actual
Date of last data collection
Anticipated
9/10/2026
Actual
Sample size
Target
100
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313419 0
Government body
Name [1] 313419 0
NHMRC (Investigator Grant)
Country [1] 313419 0
Australia
Primary sponsor type
University
Name
Australian National University
Address
The Australian National University
Canberra ACT 2600 Australia
Country
Australia
Secondary sponsor category [1] 315183 0
None
Name [1] 315183 0
Address [1] 315183 0
Country [1] 315183 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312632 0
ACT Health Human Research Ethics Committee
Ethics committee address [1] 312632 0
Ethics committee country [1] 312632 0
Australia
Date submitted for ethics approval [1] 312632 0
05/04/2023
Approval date [1] 312632 0
31/05/2023
Ethics approval number [1] 312632 0
2023.ETH.00049

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

Contacts
Principal investigator
Name 125354 0
Dr Prabhavi Perera
Address 125354 0
Monarch Mental Health Group
Unit 2/ 629, Canterbury Road,
Surrey Hills VIC 3127
Country 125354 0
Australia
Phone 125354 0
+61 498 834 952
Fax 125354 0
Email 125354 0
magelage.perera@anu.edu.au
Contact person for public queries
Name 125355 0
Prabhavi Perera
Address 125355 0
Monarch Mental Health Group
Unit 2/ 629, Canterbury Road,
Surrey Hills VIC 3127
Country 125355 0
Australia
Phone 125355 0
+61 498 834 952
Fax 125355 0
Email 125355 0
magelage.perera@anu.edu.au
Contact person for scientific queries
Name 125356 0
Prabhavi Perera
Address 125356 0
Monarch Mental Health Group
Unit 2/ 629, Canterbury Road,
Surrey Hills VIC 3127
Country 125356 0
Australia
Phone 125356 0
+61 498 834 952
Fax 125356 0
Email 125356 0
magelage.perera@anu.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.