iTBS-TMS for Bipolar Disorder

Recruiting at 1 trial location

Overseen By Kristen K Ellard, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: Mood stabilizers

Must not be taking: Benzodiazepines

Disqualifiers: Mania, Psychosis, Substance use, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

136 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach called intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to help people with bipolar disorder manage their emotions better. The researchers aim to determine if iTBS-TMS can improve brain connections related to emotion regulation and assist with emotional tasks. Participants will receive either the actual treatment or a sham version to compare effects. This trial may suit those diagnosed with bipolar I or II disorder, currently experiencing a depressive episode, and on stable medication, including a mood stabilizer, for at least one month. As an unphased trial, this study offers a unique opportunity to explore innovative treatments for emotional regulation in bipolar disorder.

Will I have to stop taking my current medications?

The trial requires that participants have a stable medication regimen for at least one month, including a mood stabilizer. However, you cannot be on benzodiazepines, as they can interfere with the treatment.

What prior data suggests that this protocol is safe for patients with bipolar disorder?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. In clinical settings, iTBS works as well as other treatments and does not present major safety issues. One study specifically on iTBS confirmed its safety, even with multiple sessions. However, some reports indicate that targeting certain brain areas with iTBS might cause mood changes in individuals with bipolar depression, so monitoring for mood shifts is important. Overall, iTBS maintains a strong safety record, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for bipolar disorder, which often involve medications like mood stabilizers and antipsychotics, Intermittent Theta Burst Stimulation (iTBS) offers a non-invasive approach. Researchers are excited about iTBS because it targets the brain's inferior parietal lobule using magnetic pulses, which is thought to help regulate mood without the side effects associated with medication. Additionally, iTBS can be administered relatively quickly, potentially providing faster symptom relief compared to traditional treatments that might take weeks to show effectiveness.

What evidence suggests that intermittent theta burst stimulation (iTBS) could be an effective treatment for bipolar disorder?

Research shows that intermittent theta-burst stimulation (iTBS) can aid in treating mood disorders like bipolar disorder. One study found that participants receiving active iTBS experienced a significant reduction in depression symptoms after one and four weeks. Other research supports that iTBS is as effective and safe for bipolar disorder as it is for regular depression. In this trial, participants will receive either active iTBS or a sham (inactive) iTBS procedure. Previous studies have demonstrated that iTBS outperformed the sham procedure in reducing symptoms, suggesting it could help individuals with bipolar disorder manage their emotions better. ^{1 3 6 7 8}

Who Is on the Research Team?

Kristen K Ellard, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with bipolar disorder. Participants will be selected based on their brain imaging scans and must have a specific connection in the brain that can be targeted by the treatment. They should be able to complete multiple sessions over several days.

Inclusion Criteria

I am between 24 and 65 years old.

Ability to provide informed consent and verifiable contact information, including current psychiatric treatment provider

Diagnostic Statistical Manual (DSM-5) defined diagnosis of bipolar I or II disorder (BD) assessed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) version 7.0.2

Exclusion Criteria

History of psychosis

I don't have metal implants, a history of seizures, or serious head injuries.

Current mania/hypomania assessed by the Young Mania Rating Scale (YMRS > 12)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 24 sessions of active or sham intermittent theta burst stimulation (iTBS) over 4 days

1 week

6 sessions/day for 4 days

Follow-up

Participants are monitored for changes in functional connectivity and behavior through fMRI and computer-based tasks

4 weeks

1 visit (in-person) for fMRI and tasks

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation (iTBS)

Trial Overview The study tests if iTBS-TMS, a non-invasive brain stimulation technique, can improve emotion regulation in bipolar patients by targeting a specific brain area identified through fMRI scans. Patients receive either real or sham TMS over four days to see if it affects their emotional control.

How Is the Trial Designed?

Group I: Active intermittent theta burst stimulation (iTBS) Experimental Treatment 1 Intervention

The Active intermittent theta burst stimulation (iTBS) arm will receive active iTBS applied to the inferior parietal lobule (IPL)

Group II: Sham intermittent theta burst stimulation (iTBS) Placebo Group 1 Intervention

The Sham intermittent theta burst stimulation (iTBS) arm will receive sham iTBS applied to the inferior parietal lobule (IPL)

Intermittent Theta Burst Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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 19 patients with acute-phase bipolar depression, continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated, with no major adverse effects reported.

Despite the treatment being safe, the efficacy of cTBS in significantly improving depression symptoms was inconclusive, as no statistically significant differences were observed between the active and sham treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study. Mallik, G., Mishra, P., Garg, S., et al.[2023]

In a study involving 31 patients with bipolar depression, intermittent theta burst stimulation (iTBS) did not show significant cognitive improvements compared to sham stimulation over four weeks.

However, there was a trend indicating increased left hippocampal volume in the active group, which correlated with improvements in nonverbal memory, suggesting potential neuroplastic changes that could support cognitive enhancement in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intermittent theta-burst transcranial magnetic stimulation on cognition and hippocampal volumes in bipolar depression. Torres, IJ., Ge, R., McGirr, A., et al.[2023]

A clinical trial involving 37 participants with acute bipolar depression found that intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex was not effective, as there were no significant differences in depression scores between the active and sham treatment groups.

The study was terminated for futility, indicating that iTBS did not show clinical benefits in reducing depression symptoms, and only a small percentage of participants responded to treatment, highlighting the need for further research on TMS protocols in bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression: A Randomized Clinical Trial. McGirr, A., Vila-Rodriguez, F., Cole, J., et al.[2021]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36841303/

Outcome of transcranial magnetic intermittent theta-burst ... In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830095

Accelerated Intermittent Theta-Burst Stimulation for ... Within-group improvements for active aiTBS indicated a significant and sustained reduction in depression severity at 1 and 4 weeks. Several ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667174325001727

Efficacy, effectiveness and safety of transcranial magnetic ... TMS is efficacious and safe in BDep, with response and remission rates on par with unipolar depression. High and low frequency protocols on left ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05849402

Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in ... The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38985492/

Accelerated Intermittent Theta-Burst Stimulation and ... In this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD.

6. sciencedirect.com sciencedirect.com/science/article/pii/S3050529124000825

A double-blind, randomized, sham-controlled clinical trial ... This randomized, double-blind, sham-controlled clinical trial evaluated the safety, tolerability, and efficacy of applying 10 sessions of iTBS, delivered twice ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777422

Efficacy of Active vs Sham Intermittent Theta Burst ... iTBS targeting the left dorsolateral prefrontal cortex is not efficacious in the treatment of acute bipolar depression and can result in mood episode switches.

8. nature.com nature.com/articles/s41591-023-02764-z

Connectivity-guided intermittent theta burst versus ... - Nature Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton ...