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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06003309




Registration number
NCT06003309
Ethics application status
Date submitted
11/07/2023
Date registered
21/08/2023
Date last updated
1/03/2024

Titles & IDs
Public title
Frequency and E-field Enhancement of ITBS for Depression (FREED)
Scientific title
Frequency and E-field Enhancement of ITBS for Depression (FREED)
Secondary ID [1] 0 0
807836
Universal Trial Number (UTN)
Trial acronym
FREED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS
Treatment: Devices - Transcranial Magnetic Stimulation (TMS) - targeted-iTBS
Treatment: Devices - Transcranial Magnetic Stimulation (TMS) - Standard-iTBS

Active comparator: The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches) - In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.

Active comparator: iTBS individualized using E-field targeting only (targeted-iTBS) - In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting.

Active comparator: Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method) - The standard iTBS will be delivered with the typical 5Hz/50Hz patterned frequencies used in the FDA-approved treatment protocol and stimulation will be delivered according to the Beam F3 targeting.


Treatment: Devices: Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS
Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.

Treatment: Devices: Transcranial Magnetic Stimulation (TMS) - targeted-iTBS
Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting.

Treatment: Devices: Transcranial Magnetic Stimulation (TMS) - Standard-iTBS
Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. The standard iTBS will be delivered with the typical 5Hz/50Hz patterned frequencies used in the FDA approved treatment protocol and stimulation will be delivered according to the Beam F3 targeting.
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from pre-treatment in fronto-parietal theta connectivity at post-treatment
Timepoint [1] 0 0
pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)

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 disorder.
* 18-80 years of age.
* Male or female.
* At least one failed antidepressant medication trial at level 3 in the Antidepressant Treatment History Form: Short Form (ATHF-SF) classification.
* Montgomery-Asberg Depression Rating Scale (MADRS) Score of >19 (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
80 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.
* Any psychotic disorder or current active psychotic symptoms.
* Patients who have intracranial implants, other medical device or condition deemed unsafe for TMS.
* Contraindication to MRI scanning.

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)
Methods used to generate the sequence in which subjects will be randomised (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
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Australian National University - Canberra
Recruitment postcode(s) [1] 0 0
2601 - Canberra
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California

Funding & Sponsors
Primary sponsor type
Other
Name
University of California, San Diego
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institutes of Health (NIH)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The investigators propose a randomized 3-arm double-blinded parallel experimental trial (20 sessions over 4 weeks) in 75 patients with TRD. The three arms include (1) the combination of a fully Individualized form of intermittent Theta Burst Stimulation (iTBS) (using BOTH the frequency and electric field (E-field) targeting approaches) (Ind-iTBS)), (2) iTBS individualized using E-field targeting only (targeted-iTBS) and (3) Standard iTBS treatment (i.e., typical iTBS localized to the dorsolateral prefrontal cortex (DLPFC) using the Beam F3 method). Electroencephalography (EEG) data will be collected at rest and during a working memory task, at baseline, and at the end of treatment along with clinical assessments of depression severity. The target engagement dependent variable of interest in these three arms will be fronto-parietal theta connectivity measured through resting-state EEG. The investigators hypothesize that stimulation with Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity than that produced with targeted-TBS and standard iTBS. Aim: To evaluate the effects of two individualized forms of iTBS (i.e., using BOTH the frequency and E-field individualization; Ind-iTBS) compared to iTBS individualized for E-field targeting only (targeted-iTBS) and standard iTBS on fronto-parietal theta connectivity. Hypotheses: (1) Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity compared to both targeted-iTBS and standard iTBS. (2) Ind-iTBS will also lead to a greater reduction in depressive symptoms (as defined by the mean reduction in Montgomery Åsberg Depression Rating Scale Scores (MADRS)) compared to both targeted-iTBS and standard iTBS.
Trial website
https://clinicaltrials.gov/study/NCT06003309
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Interventional Psychiatry
Address 0 0
Country 0 0
Phone 0 0
858-207-0938
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06003309