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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to establish how personalization of repetitive transcranial magnetic stimulation (rTMS) can change markers of brain activity and improve treatment response. To do this, all participants will receive the same active form of treatments, but some of the participants in this study will receive intermittent theta burst stimulation (iTBS) rTMS treatment with standard forms of targeting and intensity, and others will receive iTBS rTMS treatment using personalized magnetic resonance imaging (MRI) and electric field (E-field) modeling measures.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the treatment E-field Guided iTBS for Depression?

Research shows that intermittent theta burst stimulation (iTBS) is as effective as traditional repetitive transcranial magnetic stimulation (rTMS) for treating depression, including treatment-resistant cases. Studies suggest that iTBS can be delivered more quickly and may help patients achieve remission faster when applied multiple times a day. ^{1 2 3 4 5}

Is E-field Guided iTBS safe for humans?

Research shows that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated in humans, with studies reporting no adverse events in patients with depression, including those with bipolar depression. ^{2 4 5 6 7}

How is E-field Guided iTBS treatment different from other depression treatments?

E-field Guided iTBS is a unique treatment for depression because it is a noninvasive brain stimulation that can be delivered in just over 3 minutes, compared to the longer sessions required for traditional methods. It targets specific brain areas more precisely and can be administered multiple times a day, potentially leading to faster improvement in symptoms. ^{1 2 3 5 7}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

References

1. United States 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). [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]

5. England 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. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

7. Switzerland 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. [2023]