E-field Guided iTBS for Depression

Recruiting at 1 trial location

Overseen By Daphne Voineskos, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Bipolar, Psychotic, Neurological disorders, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

Duration: 6 weeks

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a brain stimulation treatment to determine if personalization enhances its effectiveness for people with depression. Participants will receive a type of repetitive transcranial magnetic stimulation (rTMS) known as intermittent theta burst stimulation (iTBS). Some participants will have their treatment tailored using MRI scans, while others will receive standard treatment. This trial targets individuals who have experienced a major depressive episode and have not responded well to antidepressants. As an unphased trial, it offers a unique opportunity to explore innovative treatment options for depression.

Will I have to stop taking my current medications?

The trial requires that you keep your current medication constant during the study.

What prior data suggests that this iTBS treatment is safe for depression?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. iTBS, a type of brain stimulation therapy, can quickly reduce symptoms of major depressive disorder by using magnetic fields to stimulate nerve cells in the brain, improving mood.

In past studies, participants experienced very few side effects, with the most common being mild headaches or scalp discomfort, which typically resolved shortly after treatment. No serious side effects were reported, indicating that this method is quite safe.

iTBS is also used in other approved treatments for depression, further supporting its safety. While this trial customizes the treatment using MRI and electric field modeling, the basic therapy has a strong record of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to enhance the effectiveness of iTBS (intermittent Theta Burst Stimulation) for treating depression. Unlike traditional methods, the trial leverages advanced E-field modeling to tailor iTBS treatment by using MRI data to pinpoint the exact spots in the brain for stimulation, potentially increasing precision and effectiveness. Meanwhile, the Beam F3 approach uses standard anatomical landmarks, offering a simpler yet effective comparison. This trial could pave the way for more personalized and efficient depression treatments, offering hope for quicker relief and better outcomes compared to existing options like medication or standard TMS therapy.

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

Research has shown that intermittent theta burst stimulation (iTBS) holds promise for treating depression. Studies have found that iTBS can quickly improve symptoms in people with major depressive disorder. In this trial, participants will be assigned to one of two treatment courses. Treatment Course A uses electric field modeling to guide iTBS, which research suggests can help predict treatment effectiveness. Treatment Course B uses standard parameters for targeting iTBS. Another review suggests that iTBS might be more effective and efficient than traditional treatments. Overall, iTBS appears to be a strong option for people with depression, especially when personalized using electric field modeling. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with major depressive disorder who haven't responded to certain antidepressants. They must score ≥18 on the HRSD-17, be outpatients, consent to treatment, and keep their current medication stable. Exclusions include unstable medical conditions, pregnancy, metal implants affecting MRI or TMS safety, inadequate English fluency, recent psychotherapy changes, certain psychiatric diagnoses or substance use disorders.

Inclusion Criteria

Patients have a Diagnostic and Statistical Manual for Mental Disorders, 5th edition major depressive episode based on the Mini International Neuropsychiatric Interview (MINI)

I am willing and able to agree to treatment.

Patients are able to adhere to the study and treatment schedules

Exclusion Criteria

Patients are participating in a new course psychotherapy initiated within the last 3 months or finishing prior to the end of scheduled treatments

Patients have a concomitant unstable medical illness

Patients present with a medical condition, medication, or laboratory abnormality that could cause a major depressive episode in the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iTBS rTMS treatment for 6 weeks, with 5 sessions per week, targeting the left dorsolateral prefrontal cortex (DLPFC).

6 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits at 1 and 4 weeks post-treatment.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• iTBS

Trial Overview The study tests personalized repetitive transcranial magnetic stimulation (rTMS) using intermittent theta burst stimulation (iTBS). Participants will receive iTBS either with standard targeting/intensity or tailored to individual brain activity markers via MRI and E-field modeling measures.

How Is the Trial Designed?

Group I: Treatment Course A: E-field Modeling Experimental Treatment 1 Intervention

Your Magnetic Resonance Image (MRI) results and rTMS calibration information (motor threshold) will be used to create a brain model and identify the targeted location, iTBS coil position and intensity for your iTBS rTMS treatment. You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.

Group II: Treatment Course B: Beam F3 Active Control 1 Intervention

The targeted iTBS rTMS treatment location and intensity will be determined via standard parameters, specifically anatomical landmarks and your rTMS calibration information (motor threshold). You will undergo iTBS rTMS treatment in this study for 6 weeks. There will be 5 iTBS treatment sessions per week, lasting approximately 3 minutes each, once daily for 5 days in a row (always Monday to Friday). Each day after treatment, you will also complete a brief set of questionnaires to track your symptoms, which will take 15 minutes. After every 5 treatments, you will complete an extra interview that will take an additional 30 minutes. There will also be two follow-up visits at 1 and 4 weeks after the end of treatment, each lasting approximately 1 hour. During these follow-up visits, you will be asked to complete a brief set of questionnaires and interviews to monitor your symptoms.

iTBS is already approved in United States for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression
• Major depressive disorder

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

In a study of 22 participants with treatment-resistant depression, the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which uses high-dose intermittent theta-burst stimulation (iTBS) guided by functional connectivity MRI, showed a remarkable remission rate of 90.5%.

The treatment was well tolerated with no negative cognitive side effects reported, suggesting that SAINT could be a safe and effective option for patients who have not responded to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Cole, EJ., Stimpson, KH., Bentzley, BS., et al.[2020]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05583747

E-field Guided iTBS for Treatment Resistant Depression The purpose of this study is to establish how personalization of rTMS can change markers of brain activity and improve treatment response in major depressive ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10427506/

Electric field distribution predicts efficacy of accelerated ... We undertook a pilot study of accelerated fMRI-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex in 25 adults aged ...

3. reporter.nih.gov reporter.nih.gov/project-details/10876920

Frequency and E-field Enhancement of iTBS for ... The overall goal of this research is to develop a more effective form of iTBS treatment for patients with TRD. Public Health Relevance Statement. Intermittent ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123003797

Accelerated intermittent theta burst stimulation in major ... aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in major depressive disorder [MDD].

5. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

6. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1215093/full

Electric field distribution predicts efficacy of accelerated ... We undertook a pilot study of accelerated fMRI-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex in 25 adults aged ...