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Trial registered on ANZCTR


Registration number
ACTRN12622001273774
Ethics application status
Approved
Date submitted
15/09/2022
Date registered
28/09/2022
Date last updated
10/02/2023
Date data sharing statement initially provided
28/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Optimizing the clinical effectiveness of dual site Theta Burst Stimulation (TBS) treatment for individuals with depression (OPTI-TBS; Study 2)
Scientific title
Optimizing the clinical effectiveness of dual site Theta Burst Stimulation (TBS) treatment for individuals with treatment-resistant depression (OPTI-TBS; Study 2)
Secondary ID [1] 307881 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
OPTI-TBS (2)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment resistant depression 327591 0
Condition category
Condition code
Mental Health 324680 324680 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed study aims to optimise the application of iITBS therapy by exploring whether enhanced outcomes are achieved with a dual site stimulation protocol. This study involves a randomised parallel design study with blinded assessment of treatment outcomes. All iTBS will be applied in triplet burst of 3 pulses at 50Hz repeated at 5Hz in 2 second trains with an eight second into train interval (total of 600 pulses).

Participants will be randomized to one of 3 treatment groups:
1. iTBS applied to the left dorsolateral prefrontal cortex (DLPFC) as localised using the Beam F3 method.
2. iTBS to the DLPFC and at a second, more posterior site, localised using the 5 cm method.
3. iTBS to a singular site on the lateral PFC with the Brainsway H1 coil (providing broad stimulation across the prefrontal cortex).

Treatment courses in the trial will consist of daily (Monday-Friday) sessions of iTBS onsite at Monarch Mental Health Group clinics for 7 weeks, totaling 35 sessions of iTBS treatment. iTBS will be administered with a MagVenture Magpro magnetic stimulator or equivalent using a 70mm figure-of-8 or the Brainsway TMS system with H1 coil. Treatment will be delivered by TMS technicians within Monarch Mental Health Group clinics across Victoria, Queensland and New South Wales. Study outcomes will be assessed at baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, end treatment and at 1, 3 and 6 month follow up and will take place via video conference calls and through electronic links to forms, carried out and overseen by research staff. Adherence to the intervention will be monitored through session attendance records.
Intervention code [1] 324397 0
Treatment: Devices
Comparator / control treatment
This Study will have an active control group (Group 1) where participants will receive the standard iTBS treatment: iTBS applied in triplet burst of 3 pulses at 50Hz repeated at 5Hz in 2 second trains with an eight second inter-train interval (total of 600 pulses), This will be administered to the left dorsolateral prefrontal cortex (DLPFC) as localised using the Beam F3 method.
Control group
Active

Outcomes
Primary outcome [1] 332502 0
Total score on the 17 item Hamilton Depression Rating Scale (HAMD).
Timepoint [1] 332502 0
The primary analysis will be on mean HAMD scores from baseline to treatment end (completion of 35 treatment sessions) for each primary comparison.
Secondary outcome [1] 413751 0
Patient Health Questionnaire-9 (PHQ-9)
Timepoint [1] 413751 0
Baseline compared to study timepoints: week 1 of treatment, week 2 of treatment, week 3 of treatment, week 4 of treatment, end of treatment (week 8 post-treatment commencement), and 1, 3 and 6 months post-treatment completion
Secondary outcome [2] 413752 0
Beck Anxiety Inventory (BAI)– self rated anxiety
Timepoint [2] 413752 0
Baseline compared to study timepoints: week 2 of treatment, week 4 of treatment, end of treatment (completion of 35 treatment sessions), and 1, 3 and 6 months post-treatment completion
Secondary outcome [3] 413753 0
Patients Global Impression of Improvement Scale (PGI-I)
Timepoint [3] 413753 0
Week 2 of treatment, week 4 of treatment, end of treatment (completion of 35 treatment sessions), and 1, 3 and 6 months post-treatment completion
Secondary outcome [4] 413754 0
Patients Global Impression of Severity Scale (PGI-S)
Timepoint [4] 413754 0
Baseline compared to study timepoints: week 2 of treatment, week 4 of treatment, end of treatment (completion of 35 treatment sessions), and 1, 3 and 6 months post-treatment completion
Secondary outcome [5] 413756 0
Assessment of Quality of Life (AQoL-8D)
Timepoint [5] 413756 0
Baseline compared to end of treatment (completion of 35 treatment sessions), and 1, 3 and 6 months post-treatment completion.
Secondary outcome [6] 413757 0
A custom questionnaire in regards to TMS tolerability and side effects
Timepoint [6] 413757 0
Conducted at Week 4 of treatment and end of treatment (completion of 35 treatment sessions).
Secondary outcome [7] 418427 0
Inventory of Depression and Anxiety Symptoms –II (IDAS-II)
Timepoint [7] 418427 0
Baseline

Eligibility
Key inclusion criteria
Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar major depressive disorder or bipolar affective disorder.

18-85 years of age.

Treatment resistant depression at Stage I of the Thase and Rush classification.

Hamilton Depression Rating Scale (HAMD) score of >17 (moderate – severe depression).

No increase or initiation of new antidepressant therapy in the four weeks prior to screening.

Demonstrated capacity to give informed consent.

Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to provide informed consent

Medically unstable patients

Concomitant neurological disorder or a history of a seizure disorder.

Patients who are pregnant or breastfeeding.

Active suicidal intent

Any psychotic disorder or current active psychotic symptoms

Patients who have intracranial implants deemed unsafe for TMS.

Significant difficulties with English communication and comprehension.

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, who have a computer generated random sequence for treatment groups, after the participant is deemed eligible and has consented for the study.
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).

Allocation to study will be based on a geographical basis, i.e. whether or not participants are attending a clinic that has specific TMS machines (e.g. Brainsway deep TMS is required for allocation to this study).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We aim to recruit a total of 240 subjects (80 per group). A sample of 148 (7.5% attribution which is conservative based on our previous studies) will provide power of 0.805 to detect a four point greater reduction in HAMD score from baseline to end of treatment between any of the 2 groups (repeated measured model, unstructured covariance matrix, significance level of 0.05). The primary outcome measure (HAMD) in study will be analysed via the fitting of linear mixed models. The repeated measurements of the primary outcome variable will be analysed by fitting linear mixed models using restricted maximum likelihood (REML) – this will allow all available data to be used without the need for imputation of missing values, the selection of the most suitable variance-covariance model for the repeated measures, using Akaike’s Information Criterion, and the investigation of commonality of any nonlinear trends over time via smoothing splines. The F-test will be used to test for a treatment by time interaction and comparisons between treatment groups at each time point will be based on t-tests that utilize the predicted means and standard errors of difference that are recovered from the fitted mixed model. Categorical outcomes (response and remission rates) will be compared using chi-squared analysis based on last observation carried forward data.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
22/02/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC

Funding & Sponsors
Funding source category [1] 312155 0
Government body
Name [1] 312155 0
NHMRC Investigator Grant
Country [1] 312155 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] 313682 0
None
Name [1] 313682 0
Address [1] 313682 0
Country [1] 313682 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311546 0
Australian National University Human Research Ethics Committee
Ethics committee address [1] 311546 0
Ethics committee country [1] 311546 0
Australia
Date submitted for ethics approval [1] 311546 0
08/09/2022
Approval date [1] 311546 0
06/12/2022
Ethics approval number [1] 311546 0
2022.ETH.00182

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

Contacts
Principal investigator
Name 121490 0
Prof Paul Fitzgerald
Address 121490 0
Australian National University (ANU)
School of Medicine and Psychology
The Australian National University, Science Rd
Canberra, ACT
2601
Country 121490 0
Australia
Phone 121490 0
+61 2 6125 2796
Fax 121490 0
Email 121490 0
paul.fitzgerald@anu.edu.au
Contact person for public queries
Name 121491 0
Paul Fitzgerald
Address 121491 0
Australian National University (ANU)
School of Medicine and Psychology
The Australian National University, Science Rd
Canberra, ACT
2601
Country 121491 0
Australia
Phone 121491 0
+61 2 6125 2796
Fax 121491 0
Email 121491 0
paul.fitzgerald@anu.edu.au
Contact person for scientific queries
Name 121492 0
Paul Fitzgerald
Address 121492 0
Australian National University (ANU)
School of Medicine and Psychology
The Australian National University, Science Rd
Canberra, ACT
2601
Country 121492 0
Australia
Phone 121492 0
+61 2 6125 2796
Fax 121492 0
Email 121492 0
paul.fitzgerald@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
The PI has not yet decided whether IPD will be made available on public directories.


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.