aiTBS for Depression

Overseen By Ian Kratter, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Mood stabilizers

Must not be taking: Rapid antidepressants

Disqualifiers: Epilepsy, Pregnancy, Substance abuse, 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: 7

Duration: 1 week

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether aiTBS, a type of brain stimulation using magnetic fields, can help people with bipolar II disorder who haven't responded to other treatments. The treatment targets a specific brain area to improve mood and reduce depression. Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcomes in treatment-resistant depression.

Will I have to stop taking my current medications?

The trial requires that you stay on a mood stabilizer regimen for at least 6 weeks before joining and continue it during the study. The protocol does not specify if you need to stop other medications, so it's best to discuss this with the study team.

Is aiTBS safe for humans?

Studies show that intermittent theta burst stimulation (iTBS), including accelerated versions like aiTBS, is generally safe for treating depression and bipolar depression, with no adverse events reported in trials. ^{1 2 3 4 5}

How is aiTBS different from other treatments for depression?

Accelerated intermittent theta-burst stimulation (aiTBS) is a unique treatment for depression because it uses magnetic pulses to stimulate specific brain areas in a shorter time (3 minutes) compared to traditional methods (37.5 minutes), potentially allowing for faster relief of symptoms. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment Accelerated Intermittent Theta-Burst Stimulation (aiTBS) for depression?

Research shows that intermittent theta burst stimulation (iTBS), a form of aiTBS, is effective for treating major depressive disorder and treatment-resistant depression. Studies indicate that multiple daily sessions of iTBS can help patients achieve remission more quickly, although the effects may not last long without ongoing treatment. ^{1 2 3 6 8}

Who Is on the Research Team?

Nolan Williams, MD

Principal Investigator

Stanford University

Bora Kim, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with bipolar II disorder currently experiencing a major depressive episode, who haven't responded to standard treatments. They must be in good health, not have hypomania or psychosis, and women must use effective contraception. Excluded are those with metal in their head, pacemakers, substance abuse issues, severe insomnia, certain mental health conditions like anxiety disorders or personality disorders, recent suicidal behavior or thoughts.

Inclusion Criteria

In good general health, as ascertained by medical history

Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information

Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) or psychosis

Exclusion Criteria

Shrapnel or any ferromagnetic item in the head

My movement disorder won't interfere with treatment.

Any other indication the Principal Investigator feels would comprise data

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated intermittent theta-burst stimulation (aiTBS) to the left dorsolateral prefrontal cortex (L-DLPFC) with 10 sessions administered daily over 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in depressive symptoms and neural functional connectivity

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Intermittent Theta-Burst Stimulation (aiTBS)

Trial Overview The study tests accelerated intermittent theta-burst stimulation (aiTBS) targeting the left dorsolateral prefrontal cortex to treat treatment-resistant depression in bipolar II disorder patients. It's a double-blind trial comparing active aiTBS against sham (placebo) aiTBS using the MagPro rTMS system.

How Is the Trial Designed?

Group I: Active aiTBS Active Control 1 Intervention

Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.

Group II: Sham aiTBS Placebo Group 1 Intervention

Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.

Accelerated Intermittent Theta-Burst Stimulation (aiTBS) is already approved in United States for the following indications:

Approved in United States as aiTBS for:

• Treatment-resistant depression of bipolar II disorder

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a study of 50 depressed patients undergoing accelerated intermittent theta burst stimulation (aiTBS), baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was found to significantly correlate with immediate clinical responses to treatment.

Longitudinal changes in cortical thickness in the right cACC also predicted delayed clinical responses, suggesting that this brain region could serve as a biomarker for determining the effectiveness of aiTBS in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. Baeken, C., van Beek, V., Vanderhasselt, MA., et al.[2022]

In a study involving 72 patients with major depressive disorder, two daily sessions of prolonged intermittent theta-burst stimulation (piTBS) over two weeks showed significantly more responders compared to a sham treatment, indicating its efficacy as an antidepressant option.

However, the study found no evidence that longer piTBS sessions led to greater improvements in depression scores compared to other treatments, suggesting that while piTBS is effective, increasing treatment duration does not enhance its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study. Li, CT., Cheng, CM., Lin, HC., 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]

Accelerated, high-dose intermittent theta burst stimulation (iTBS) showed promising results in treating highly treatment-resistant depression, with most patients achieving remission after treatment.

However, the effects were short-lived, as all patients experienced relapse within two weeks, indicating a need for improved treatment strategies that enhance the durability of the therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? Caulfield, KA.[2021]

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 involving 50 patients with major depressive disorder (MDD), accelerated intermittent theta-burst stimulation (aiTBS) did not significantly affect reward responsiveness during a learning task, regardless of the patients' levels of anhedonia.

However, brain imaging revealed that aiTBS treatment altered neural activity in the reward system differently based on anhedonia severity, with low anhedonic patients showing decreased activity and high anhedonic patients showing increased activity after one week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia. Duprat, R., Wu, GR., De Raedt, R., et al.[2019]

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) 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]

Citations

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

Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study. [2023]

3. 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]

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

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? [2021]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia. [2019]

7. France pubmed.ncbi.nlm.nih.gov

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

8. 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]