Low Frequency rTMS for Bipolar Depression

(FLARE Trial)

Not yet recruiting at 1 trial location

Overseen By Mawahib Semeralul

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Tyler Kaster

Must be taking: Non-anticonvulsant mood stabilizers

Must not be taking: Anticonvulsants, High-dose lorazepam

Disqualifiers: Substance use, Schizophrenia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 32

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with bipolar depression who haven't responded to other treatments. Participants will receive low-frequency rTMS (repetitive transcranial magnetic stimulation), a non-invasive brain stimulation, to determine its safety and effectiveness in reducing depression symptoms. The trial seeks individuals with bipolar disorder who are currently experiencing a depressive episode and have found little relief from other treatments. Participants should not be in a mixed or manic episode and must commit to the treatment schedule. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop taking my current medications for the trial?

The trial does not specify that you need to stop taking your current medications, but you must not have started or increased any psychotropic medications for depression in the 4 weeks before screening. You must also be on a specific mood stabilizer like lithium or quetiapine, and cannot be taking anticonvulsants or more than 2 mg of lorazepam daily.

What prior data suggests that this low frequency rTMS is safe for individuals with bipolar depression?

Research has shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) on the right side of the front part of the brain is generally safe. Studies indicate it usually causes only mild side effects and does not harm brain function. This treatment has been tested on individuals with treatment-resistant depression, including teenagers, and has been well-tolerated. Some individuals might experience minor discomfort or irritation on the scalp, but serious side effects are rare. These findings suggest that this treatment is safe, although individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for bipolar depression involve medications like mood stabilizers, antipsychotics, or antidepressants, which can take weeks to show effectiveness and may come with side effects. But low frequency rTMS (repetitive Transcranial Magnetic Stimulation) offers a different approach. This treatment targets the brain's right dorsolateral prefrontal cortex using magnetic fields to stimulate nerve cells. Researchers are excited because this non-invasive method could provide faster relief with fewer side effects, offering a promising alternative for those who haven't found success with traditional medications.

What evidence suggests that low frequency rTMS is effective for bipolar depression?

Studies have shown that low frequency repetitive transcranial magnetic stimulation (LFR rTMS) on a specific brain area can improve symptoms in people with bipolar depression unresponsive to other treatments. In this trial, participants will receive low frequency (1Hz) rTMS to the Right Dorsolateral Prefrontal Cortex. Research indicates that this method is as effective as other rTMS types targeting different brain areas. The treatment stimulates certain brain pathways, potentially improving mood. Some studies suggest it offers benefits similar to standard antidepressants, making it a promising option for those who haven't found relief with other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Tyler Kaster

Principal Investigator

CAMH

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-resistant Bipolar Depression (BD-DE) who haven't improved after other therapies like iTBS or sham treatment. Participants should be able to attend daily sessions for 30 days and follow-ups.

Inclusion Criteria

Must pass the TMS adult safety screening questionnaire

I haven't started or increased depression meds in the last 4 weeks.

I understand the details of the clinical trial and can agree to participate.

Exclusion Criteria

I am not currently taking any anticonvulsant medication.

Must not have a history of MINI diagnosis of a substance use disorder (other than nicotine and/or caffeine) within the last 3 months

I have not had unsuccessful ECT treatment for my current health issue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 30 days of low frequency rTMS treatment for bipolar depression

4 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low Frequency Right Dorsolateral Pre Frontal Cortical Repetitive TMS

Trial Overview The study tests low frequency repetitive Transcranial Magnetic Stimulation (rTMS) on the right Dorsolateral Pre Frontal Cortex. It aims to see if this can help those with BD-DE when standard treatments fail, measuring depression and mania symptoms over time.

How Is the Trial Designed?

Group I: Low frequency (1Hz) rTMS to the Right Dorsolateral Prefrontal Cortex Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Tyler Kaster

Lead Sponsor

The Poul Hansen Family Centre for Depression

Collaborator

University Health Network (UHN)

Collaborator

Trials

1

Recruited

40+

Toronto Western Hospital, Canada

Collaborator

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06986460

Low Frequency Right Dorsolateral Pre Frontal Cortical ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11999845/

Efficacy and safety of low-frequency repetitive transcranial ... This study aims to examine the efficacy and safety of 1-Hz rTMS to the right prefrontal cortex of patients with treatment-resistant bipolar depression. rTMS for ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125001060

Clinical effectiveness of switching to right lateral ... Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for ...

4. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.997259/full

Low frequency repetitive transcranial magnetic stimulation ... These findings demonstrate that LF rTMS to the right DLPFC was able to stimulate the cortico-striato-thalamo-cortical pathway, which is ...

5. nature.com nature.com/articles/npp2012237

A Meta-Analysis of Randomized, Double-Blind and Sham ... LF-rTMS is a promising treatment for MD, as it provides clinically meaningful benefits that are comparable to those of standard antidepressants and high- ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724018317

Efficacy and safety of low-frequency repetitive transcranial ... LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9565480/

Low frequency repetitive transcranial magnetic stimulation to ... Low-frequency rtms over right dorsolateral prefrontal cortex in the treatment of resistant depression: cognitive improvement is independent ...