rTMS for Treatment-Resistant Depression

(BioTMS Trial)

Recruiting at 2 trial locations

Overseen By Lindsay Victoria, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Weill Medical College of Cornell University

Must not be taking: Bupropion, Tricyclic antidepressants

Disqualifiers: Suicide risk, Long depressive episode, PTSD, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8-10 weeks

348 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for people with depression that hasn't responded to other treatments. It uses repetitive transcranial magnetic stimulation (rTMS), which involves magnets stimulating the brain. Researchers aim to determine if brain scans can enhance this treatment's effectiveness. Individuals with depression who haven't found relief with at least one antidepressant and don't have other major psychiatric conditions like PTSD might be suitable for the trial. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to a promising treatment's journey to becoming widely available.

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

You must either stop or maintain the same daily dose of any depression medication for at least 4 weeks before joining the trial and throughout its duration.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating depression. Studies have found that the risk of seizure is less than 1%, which is very low. Most people experience only mild side effects, such as headaches, which usually resolve quickly. The FDA has already approved this treatment for depression, indicating it has undergone safety testing. Overall, patients tolerate rTMS well, making it a promising option for those whose depression hasn't improved with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about repetitive Transcranial Magnetic Stimulation (rTMS) for treatment-resistant depression because it offers a targeted approach that could be more effective for individual patients. Unlike traditional treatments like antidepressants or electroconvulsive therapy, rTMS uses magnetic fields to stimulate specific brain regions linked to depression. In this study, the innovative approach involves tailoring the stimulation to target the exact brain area thought to be most beneficial for each patient's unique depression subtype, offering a more personalized treatment option. This precision could lead to faster, more effective relief for those who haven't responded to existing therapies.

What evidence suggests that this trial's treatments could be effective for treatment-resistant depression?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help people with depression that hasn't improved with other treatments. In this trial, participants will be assigned to different treatment arms to evaluate the effectiveness of rTMS. One study found that about 36% of patients experienced a significant improvement in their depression symptoms. Additionally, about 85% of patients who used rTMS as their only treatment did not see their symptoms return within 24 weeks. Research also suggests that rTMS can lead to fewer hospital visits and lower healthcare costs. Overall, rTMS appears promising for those with treatment-resistant depression. ^{1 2 6 7 8}

Who Is on the Research Team?

Conor Liston, MD, PhD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Adults aged 22-65 with moderate to severe depression, who haven't improved after trying at least one antidepressant, can join this trial. They must be fluent in English and able to have an MRI safely. Participants should not change their antidepressant dose during the study and must consent to team communication with their clinicians.

Inclusion Criteria

I can safely undergo an MRI scan.

Fluent in English

Major Depressive Disorder (by M.I.N.I., Diagnostic Statistical Manual V (DSM-V criteria)); Verification by evaluation by licensed study psychiatrist or psychologist

Exclusion Criteria

Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening

I have had brain surgery for a neurological or mental health issue.

I have major depression and Vagus Nerve Stimulation didn't work for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive biotype-guided or standard-of-care rTMS treatment targeting the DLPFC or DMPFC

8-10 weeks

Multiple sessions per week

Follow-up

Participants are monitored for changes in depression severity and resting state fMRI connectivity

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The trial is testing whether brain scans (fMRI) can help optimize rTMS treatment for depression. It explores how rTMS affects brain networks by using these scans before and after therapy sessions.

How Is the Trial Designed?

Group I: Targeted Side Arm Experimental Treatment 1 Intervention

iTBS rTMS targeting the area of the brain (DLPFC or dorsomedial prefrontal cortex DMPFC)) that we hypothesize will be most effective for that subject's biotype (confirmation arm).

Group II: Standard of Care Active Control 1 Intervention

FDA-cleared, standard-of-care iTBS repetitive Transcranial Magnetic Stimulation targeting the left dorsolateral prefrontal cortex (DLPFC), regardless of the depression subtype (biotype) determined by a magnetic resonance imaging (MRI) scan.

Group III: Opposite Side Arm Active Control 1 Intervention

iTBS rTMS targeting the opposite site (DLPFC or DMPFC) than the one we hypothesize will be most effective for that subject's biotype (disconfirmation arm).

Repetitive Transcranial Magnetic Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10375664/

Efficacy of repetitive transcranial magnetic stimulation ... Meta-analysis results: remission rates. Data on remission rates were available from 9 studies. The overall remission rate was 35.71% (120/336) ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835319

Repetitive Transcranial Magnetic Stimulation as ... The relapse prevention success rate at 24 weeks in the rTMS monotherapy group was approximately 85%, whereas prior literature indicates that the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001128

Treatment expectations and clinical outcomes following ... In a series of 177 patients with TRD, positive pre-treatment expectations were associated with higher odds of remission and a reduction in depression symptoms ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224075/

Resource utilization and economic outcomes following ... This study suggests that patients who receive rTMS for treatment-resistant depression required fewer high acuity hospital visits and incurred less expensive ...

5. nature.com nature.com/articles/s41398-025-03380-w

Predictive modeling of response to repetitive transcranial ... Findings presented in this study underscore the substantial variability in depression responses and remission, despite rTMS efficacy, and the ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S016517812500215X

Safety and efficacy of Deep TMS for adolescent depression ... A comprehensive review of TMS safety reported a seizure risk of less than 1 % overall, with most adverse events being mild and transient, such as headaches and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12011827/

Impact of repetitive transcranial magnetic stimulation on ... rTMS reduced depressive symptoms in TRD patients, with modest cognitive benefits. Baseline BDNF did not predict outcomes, though the lack of ...

8. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Results. If rTMS works for you, your depression symptoms may improve or go away completely. Symptom relief may take a few weeks of treatment.