Bipolar Depression Depressed PhasePhase 3FLARENCT06986460
Low Frequency Right Dorsolateral Pre Frontal Cortical Repetitive TMS for Bipolar Depression
A Phase 3 study testing MagPro X100/R30 stimulator, Cool-B70 coil in people with Bipolar Depression Depressed Phase, run by Tyler Kaster at 2 sites in Canada.
Trial summary
The purpose of this trial is to conduct an adequately powered clinical trial of once daily LFR for individuals diagnosed with treatment-resistant BD-DE who have not responded to iTBS or sham treatment applied to the left DLPFC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bipolar Depression Depressed Phase
- What is being tested?
- MagPro X100/R30 stimulator, Cool-B70 coil
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesCanada
- Study dates
- 27 May 2025to May 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be deemed to have capacity to provide informed consent;
- Must be an outpatient;
- Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI) assessed during TRIBE trial participation with no contradictory evidence that the current episode is depressed from FLARE trial screening assessments (YMRS>10/PHQ-9 <10);
- older than 18 years;
- failure to achieve a clinical response within the TRIBE study (CTO#: 4343) defined as ≤50% response from baseline to 6 weeks on the HRSD-17.
- Score ≥10 on PHQ-9 at both (i) the 6 weeks follow-up in the TRIBE trial and (ii) at screening;
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- ≤3 months from completion of the TRIBE study;
- not currently experiencing a mixed or manic episode (YMRS ≤10);
- no increase or initiation of psychotropic medication with intention of treating depressive symptoms in the 4 weeks prior to screening. This excludes targeted treatment of insomnia with trazodone, melatonin, low-dose doxepin [3-6mg], low-dose benzodiazepines [≤2mg lorazepam daily equivalent], non-benzodiazepine benzodiazepine receptor agonists, or orexin antagonists;
- currently receiving treatment with one of the following non-anticonvulsant mood stabilizer with evidence for prevention of mania: lithium, quetiapine, asenapine, aripiprazole, paliperidone (>6mg), risperidone, olanzapine, ziprasidone, haloperidol, clozapine (lurasidone and cariprazine are excluded due to lack of evidence for preventing mania);
- able to adhere to the treatment schedule;
- pass the TMS adult safety screening questionnaire.
Who cannot join
- have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months;
- have a concomitant major unstable medical illness;
- have active suicidal intent;
- are pregnant or intend to get pregnant during the study;
- have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;
- have psychotic symptoms within the current episode;
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- have a MINI anxiety disorder, trauma-related disorder, obsessive compulsive disorder, or personality disorder assessed by a study investigator to be primary and/or causing greater impairment than BD-DE;
- failure of an adequate acute course of ECT as defined by ATHF-SF during the current episode;
- have any clinically significant neurological disorder (e.g., recent major cerebrovascular accident), or any history of seizure except those therapeutically induced by ECT or with clear precipitant (e.g., febrile seizure of childhood, alcohol withdrawal, etc.);
- have any intracranial implant (e.g., aneurysm clips, shunts, stimulators,) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
- if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study;
- have a clinically significant laboratory abnormality, in the opinion of the one of the principal investigators;
- are currently taking lorazepam ≥2 mg daily (or equivalent) due to the potential to limit rTMS efficacy;
- are currently taking, any dose of an anticonvulsant due to the potential to limit rTMS efficacy;
- if anticonvulsants have been discontinued prior to screening, at least 5 half-lives have elapsed until screening to allow sufficient drug clearance;
- have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
- participant was withdrawn from the TRIBE study due to safety concerns or at the discretion of the PI.
- any history of substance use in the last 4 weeks which poses a safety concern to undergo rTMS as assessed by the PI's review of responses to the trial's 'Substance Use Screening Questions Form'.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
University Health Network Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Eileen Lam, 437-553-0367, Eileen.lam@uhn.ca
- Recruiting
Centre For Addiction and Mental Health (CAMH)
Toronto, Ontario, M6J 1H1
Hannah Taalman, 416-535-8501, hannah.taalman@camh.ca
Mawahib Semeralul, 416-535-8501 ext. 30210, mawahib.semeralul@camh.ca
About this study
The purpose of this trial is to conduct an adequately powered clinical trial of once daily LFR for individuals diagnosed with treatment-resistant BD-DE who have not responded to iTBS or sham treatment applied to the left DLPFC. This work will develop the evidence supporting the use of LFR rTMS for individuals with treatment-resistant BD-DE who currently have limited treatment options to alleviate their suffering. Participants will come for 30 days of LFR, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.
- Conditions
- Bipolar Depression Depressed Phase
- Being tested
- MagPro X100/R30 stimulator, Cool-B70 coil
- Keywords
- rTMS, Bipolar Depression, treatment-resistant, LFR
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagPro X100/R30 stimulator, Cool-B70 coilDevice
1Hz rTMS delivered to the right DLPFC
| Study group | Role | What they receive |
|---|---|---|
| Low frequency (1Hz) rTMS to the Right Dorsolateral Prefrontal Cortex | Experimental | Individuals will all receive 30 treatments of low frequency (1Hz) rTMS delivered to the Right Dorsolateral Prefrontal Cortex. rTMS treatment will be delivered using the MagPro X100/R30 stimulator and use the Cool-B70 coil (MagVenture, Farum, Denmark), a figure 8 coil with active cooling. Receives: Device: MagPro X100/R30 stimulator, Cool-B70 coil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
Our primary analysis will be observational, and will calculate the change of the HRSD-17 score from baseline to completion of treatment (i.e., 6 weeks) as the primary outcome. Our primary analysis will be a student's paired t-test to compare the change from baseline to after 6 weeks of treatment with alpha set to 0.05. We will also report the standardized difference to determine the magnitude of change from baseline to completion of treatment.
Measured: 6 weeks
Secondary outcomes (1)
Symptoms of hypomania/mania
Our secondary analysis will also be observational, and will calculate the change of the YMRS score from baseline to completion of treatment (i.e., 6 weeks) as a secondary outcome. Our primary analysis will be a student's paired t-test to compare the change from baseline to after 6 weeks of treatment with alpha set to 0.05. We will also report the standardized difference to determine the magnitude of change from baseline to completion of treatment.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2025
- Study start27 May 2025
- Primary completionMay 2030 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar Depression Depressed PhaseStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label trial to determine if 1Hz rTMS, delivered to the right DLPFC results in a significant reduction of depressive symptoms for individuals with a treatment-resistant bipolar disorder depressive episode (BD-DE) who have not previously responded in the TRIBE study (CTO#: 4343).
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tyler Kaster
- Sponsor type
- University, hospital or other
- Collaborators
- The Poul Hansen Family Centre for Depression, Toronto Western Hospital, Canada, University Health Network, Toronto
- Responsible party
- Sponsor-investigator, Tyler Kaster, Centre for Addiction and Mental Health
- Investigators
- Tyler Kaster, Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06986460
- Sponsor's protocol ID
- 4957
- Acronym
- FLARE
- Status last verified
- Oct 2026
- First submitted
- 15 May 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No sharing of IPD, only de-identified. However, we are using ICES databases and not sure how this may apply.
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Frequency Right Dorsolateral Pre Frontal Cortical Repetitive TMS for Bipolar Depression
- ClinicalTrials.gov ID
- NCT06986460
- Acronym / sponsor ID
- FLARE / 4957
- Conditions
- Bipolar Depression Depressed Phase
- Keywords
- rTMS, Bipolar Depression, treatment-resistant, LFR
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Tyler KasterUniversity, hospital or other
- Collaborators
- The Poul Hansen Family Centre for Depression, Toronto Western Hospital, Canada, University Health Network, Toronto
- Study start
- 27 May 2025 (actual)
- Primary completion
- May 2030 (estimated)
- Study completion
- May 2030 (estimated)
- First posted
- 23 May 2025 (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 purpose of this trial is to conduct an adequately powered clinical trial of once daily LFR for individuals diagnosed with treatment-resistant BD-DE who have not responded to iTBS or sham treatment applied to the left DLPFC. This work will develop the evidence supporting the use of LFR rTMS for individuals with treatment-resistant BD-DE who currently have limited treatment options to alleviate their suffering. Participants will come for 30 days of LFR, with a 6-week follow-up period. Symptoms of depression (for determining treatment efficacy) and mania (for determining treatment safety) will be assessed using the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Young Mania Rating Scale (YMRS) every five treatments during the treatment course, and at 1 week and 6 week after treatment completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label trial to determine if 1Hz rTMS, delivered to the right DLPFC results in a significant reduction of depressive symptoms for individuals with a treatment-resistant bipolar disorder depressive episode (BD-DE) who have not previously responded in the TRIBE study (CTO#: 4343).
| Arm | Type | Receives |
|---|---|---|
| Low frequency (1Hz) rTMS to the Right Dorsolateral Prefrontal Cortex | Experimental | Device: MagPro X100/R30 stimulator, Cool-B70 coilIndividuals will all receive 30 treatments of low frequency (1Hz) rTMS delivered to the Right Dorsolateral Prefrontal Cortex. rTMS treatment will be delivered using the MagPro X100/R30 stimulator and use the Cool-B70 coil (MagVenture, Farum, Denmark), a figure 8 coil with active cooling. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Must be deemed to have capacity to provide informed consent;
- Must be an outpatient;
- Have a DSM 5 diagnosis of bipolar disorder (type I or II), current episode depressed confirmed by Mini-International Neuropsychiatric Interview version 7.0.2 (MINI) assessed during TRIBE trial participation with no contradictory evidence that the current episode is depressed from FLARE trial screening assessments (YMRS>10/PHQ-9 <10);
- older than 18 years;
- failure to achieve a clinical response within the TRIBE study (CTO#: 4343) defined as ≤50% response from baseline to 6 weeks on the HRSD-17.
Key exclusion criteria (18 listed)
- have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months;
- have a concomitant major unstable medical illness;
- have active suicidal intent;
- are pregnant or intend to get pregnant during the study;
- have a lifetime MINI diagnosis of schizophrenia or schizoaffective disorder;
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 |
|---|---|---|
| MagPro X100/R30 stimulator, Cool-B70 coil1Hz rTMS delivered to the right DLPFC | Device | Low frequency (1Hz) rTMS to the Right Dorsolateral Prefrontal Cortex |
Primary outcome
Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17)
Time frame: 6 weeks
Our primary analysis will be observational, and will calculate the change of the HRSD-17 score from baseline to completion of treatment (i.e., 6 weeks) as the primary outcome. Our primary analysis will be a student's paired t-test to compare the change from baseline to after 6 weeks of treatment with alpha set to 0.05. We will also report the standardized difference to determine the magnitude of change from baseline to completion of treatment.
1 secondary outcome
Symptoms of hypomania/mania
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: No. No sharing of IPD, only de-identified. However, we are using ICES databases and not sure how this may apply.
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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.
Tyler Kaster principal investigator
CAMH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing MagPro X100/R30 stimulator, Cool-B70 coil in people with Bipolar Depression Depressed Phase, run by Tyler Kaster at 2 sites in Canada.
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 12 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 5 Oct 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 Canada. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hannah Taalman (416-535-8501, Hannah.taalman@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change on the 17-item Hamilton Rating Scale for Depression (HRSD-17) (time frame: 6 weeks). 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 5 Oct 2026.