Major Depressive DisorderFREEDNCT06003309
Frequency and E-field Enhancement of ITBS for Depression (FREED)
A study testing Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS, Transcranial Magnetic Stimulation (TMS) - targeted-iTBS and Transcranial Magnetic Stimulation (TMS) - Standard-iTBS in people with Major Depressive Disorder, run by University of California, San Diego at 2 sites in 2 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS, Transcranial Magnetic Stimulation (TMS) - targeted-iTBS and Transcranial Magnetic Stimulation (TMS) - Standard-iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 31 Aug 2023to 30 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 ≥ 20 (moderate-severe depression).
- No increase or initiation of new antidepressant therapy in the four weeks prior to screening.
- Demonstrated capacity to give informed consent.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of California, San Diego
La Jolla, California, 92093
About this study
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.
- Conditions
- Major Depressive Disorder
- Being tested
- Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS, Transcranial Magnetic Stimulation (TMS) - targeted-iTBS, Transcranial Magnetic Stimulation (TMS) - Standard-iTBS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBSDevice
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.
Transcranial Magnetic Stimulation (TMS) - targeted-iTBSDevice
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.
Transcranial Magnetic Stimulation (TMS) - Standard-iTBSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches) | Active comparator | 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. Receives: Device: Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS |
| iTBS individualized using E-field targeting only (targeted-iTBS) | Active comparator | In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting. Receives: Device: Transcranial Magnetic Stimulation (TMS) - targeted-iTBS |
| Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method) | Active comparator | 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. Receives: Device: Transcranial Magnetic Stimulation (TMS) - Standard-iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from pre-treatment in fronto-parietal theta connectivity at post-treatment
Source-localized fronto-parietal theta connectivity will be calculated from resting EEG
Measured: pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start31 Aug 2023
- Primary completion30 Dec 2025
- Study completion30 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Zafiris Daskalakis, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06003309
- Sponsor's protocol ID
- 807836
- Acronym
- FREED
- Status last verified
- Feb 2026
- First submitted
- 11 Jul 2023
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frequency and E-field Enhancement of ITBS for Depression (FREED)
- ClinicalTrials.gov ID
- NCT06003309
- Acronym / sponsor ID
- FREED / 807836
- Conditions
- Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 31 Aug 2023 (actual)
- Primary completion
- 30 Dec 2025 (actual)
- Study completion
- 30 Dec 2025 (actual)
- First posted
- 21 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches) | Active comparator | Device: Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBSIn 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. |
| iTBS individualized using E-field targeting only (targeted-iTBS) | Active comparator | Device: Transcranial Magnetic Stimulation (TMS) - targeted-iTBSIn the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modeling and coordinate-based cortical targeting. |
| Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method) | Active comparator | Device: Transcranial Magnetic Stimulation (TMS) - Standard-iTBSThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 ≥ 20 (moderate-severe depression).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBSRepetitive 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. | Device | The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches) |
| Transcranial Magnetic Stimulation (TMS) - targeted-iTBSRepetitive 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. | Device | iTBS individualized using E-field targeting only (targeted-iTBS) |
| Transcranial Magnetic Stimulation (TMS) - Standard-iTBSRepetitive 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. | Device | Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method) |
Primary outcome
Change from pre-treatment in fronto-parietal theta connectivity at post-treatment
Time frame: pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)
Source-localized fronto-parietal theta connectivity will be calculated from resting EEG
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS, Transcranial Magnetic Stimulation (TMS) - targeted-iTBS and Transcranial Magnetic Stimulation (TMS) - Standard-iTBS in people with Major Depressive Disorder, run by University of California, San Diego at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from pre-treatment in fronto-parietal theta connectivity at post-treatment (time frame: pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.