Accelerated TBS for Adolescent Depression

Overseen By Can Ozger

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Paul E. Croarkin

Must not be taking: Neuroleptics, Tricyclics

Disqualifiers: Psychotic disorder, Bipolar, Epilepsy, others

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

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

Compensation: Varies

Number of Visits: 30

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new type of brain stimulation called theta burst stimulation (TBS) to determine its effectiveness in reducing suicidal thoughts in adolescents with Major Depressive Disorder (MDD). Researchers aim to discover if this treatment can improve symptoms over a short period of 10 days and continue to provide benefits over a year. Participants will receive either the real TBS treatment using the MagVenture TMS Therapy System with Theta Burst Stimulation or a sham (fake) version for comparison. The trial seeks adolescents who have experienced a current episode of depression for at least 4 weeks, have severe symptoms, and have had thoughts of self-harm. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatment options for adolescents with MDD.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. If you are on an antidepressant, you can continue taking it if recommended by your doctor and agreed upon by you and your parents. However, certain medications that lower the seizure threshold, like neuroleptic agents and tricyclic antidepressants, may not be allowed.

What prior data suggests that this TMS treatment is safe for adolescents with depression?

Research has shown that theta burst stimulation (TBS) is generally safe for teenagers with depression. Similar treatments, such as transcranial magnetic stimulation (TMS), have been safely used in teens. The MagVenture TMS Therapy System is specifically approved for adolescents aged 15 to 21 with major depressive disorder (MDD).

Studies suggest that TBS can help reduce suicidal thoughts in adults with MDD, and these treatments are usually well-tolerated. While the long-term safety in children is still being studied, TBS appears to be as safe for kids as it is for adults. Serious side effects have not been commonly reported in studies involving teenagers.

Overall, TBS seems to be a safe option, but like any treatment, it may carry some risks or mild side effects. Discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the MagVenture TMS Therapy System with Theta Burst Stimulation (TBS) for adolescent depression because it offers a faster and potentially more effective approach than traditional treatments like antidepressants or standard TMS. Unlike most depression treatments that can take weeks to show results, this accelerated TBS protocol is designed to produce effects in just 10 days. This method uses a unique pattern of magnetic pulses to stimulate specific areas of the brain associated with mood regulation, providing a new mechanism of action that could be more efficient and targeted compared to existing therapies.

What evidence suggests that this TMS treatment might be an effective treatment for adolescent depression?

Research shows that theta burst stimulation (TBS), a type of brain stimulation, may help treat depression. Studies have found that TBS can greatly reduce suicidal thoughts in adults with Major Depressive Disorder (MDD). Early research in teenagers also suggests it works quickly to relieve depression, which could be beneficial for them. In this trial, participants will receive either the active MagVenture TMS Therapy system with TBS or a sham version. The MagVenture TMS Therapy system, which includes TBS, is already approved as an additional treatment for MDD in teens aged 15 to 21. These findings suggest that TBS could effectively improve depression symptoms and reduce suicidal thoughts. ^{2 3 4 6 7}

Who Is on the Research Team?

Paul E Croarkin, DO, MS

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adolescents aged 12-18 with Major Depressive Disorder and suicidal thoughts, who score a minimum on the C-SSRS severity scale. They must be able to consent or have guardian consent, not show significant improvement in depressive symptoms before starting, and can be on antidepressants if agreed upon. Exclusions include low IQ, drug use, epilepsy history, brain trauma/surgery, certain metal implants, pregnancy/nursing status.

Inclusion Criteria

Inpatients or outpatients

I, or my guardian if I'm under 18, agree to participate in the trial.

I meet the safety requirements for TMS treatment.

Exclusion Criteria

You have taken any experimental medication within the past 4 weeks.

You have been diagnosed with a serious mental illness like schizophrenia, bipolar disorder, anorexia or bulimia, or have had problems with drug or alcohol abuse in the past year (except for caffeine and tobacco).

Inability to adhere to the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sequential bilateral accelerated theta burst stimulation (aTBS) or sham TBS for suicidal ideation in adolescents with MDD. Three TBS sessions are administered daily for 10 days, 5 days per week, for a total of 30 sessions.

2 weeks

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of suicidal ideation and emergency department visits.

12 months

Monthly assessments

What Are the Treatments Tested in This Trial?

Interventions

• MagVenture TMS Therapy System w/Theta Burst Stimulation
• Sham MagVenture TMS Therapy System w/Theta Burst Stimulation

Trial Overview The trial is testing theta burst stimulation (TBS) using the MagVenture TMS Therapy System for reducing suicidal ideation in adolescents with depression over a period of 10 days and monitoring outcomes for one year. Participants will either receive real TBS treatment or a sham (fake) version as part of the study.

How Is the Trial Designed?

Group I: Active Accelerated Sequential Bilateral Theta Burst Stimulation Experimental Treatment 1 Intervention

Subjects will receive 11.5 minutes sessions of sequential bilateral TBS at 80% motor threshold, 3 times daily (1 hour apart) for 10 days in total (5 days per week).

Group II: Sham Comparison Group Placebo Group 1 Intervention

Subjects will receive 3 daily bilateral sessions of sham TBS. Sessions in the comparison group are 11.5 minutes in duration, three times daily, for 10 days total (5 days per week).

MagVenture TMS Therapy System w/Theta Burst Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as MagVenture TMS Therapy System w/Theta Burst Stimulation for:

• Major Depressive Disorder (MDD) with suicidal ideation

Approved in European Union as MagVenture TMS Therapy System w/Theta Burst Stimulation for:

• Major Depressive Disorder (MDD) with suicidal ideation

Who Is Running the Clinical Trial?

Paul E. Croarkin

Lead Sponsor

Trials

4

Recruited

100+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

Intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) are equally effective and safe for treating patients with treatment-resistant major depressive disorder, based on a comprehensive meta-analysis.

iTBS may be a more practical option in clinical settings because it requires less stimulation intensity and shorter treatment times compared to HF-rTMS, making it potentially more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. Kishi, T., Sakuma, K., Matsuda, Y., et al.[2023]

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., et al.[2022]

In a case series of 9 patients with major depressive disorder and bipolar disorder, accelerated theta-burst rTMS treatment over 8 days led to significant reductions in depression symptoms, as measured by the CES-D and CGI scales.

The treatment was well tolerated, with mild headaches being the most common side effect, and five patients achieving at least a 50% reduction in symptoms by the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. Bröcker, E., van den Heuvel, L., Seedat, S.[2020]

Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), has been shown to be effective in treating major depression, with a response rate effect size of 0.38 and a remission rate effect size of 0.20 based on a meta-analysis of 10 studies involving 591 participants.

TBS is not only effective but also has a favorable safety profile, showing no major adverse events, and is more efficient in terms of time and energy compared to standard rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of theta-burst stimulation for major depression: A systematic review and meta-analysis. Chu, HT., Cheng, CM., Liang, CS., et al.[2021]

Citations

1. magventure.com magventure.com/

MagVenture TMS Machines The MagVenture TMS Therapy™ system is now indicated as an adjunct treatment for Major Depressive Disorder (MDD) in adolescent patients aged 15 to 21 who have ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The purpose of this study is to gather information regarding the use of a new type of transcranial magnetic stimulation (TMS) called theta burst stimulation ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10101506/

Sequential bilateral accelerated theta burst stimulation in ... In the past decade, studies of TMS interventions found that bilateral TMS strongly reduced suicidal ideation in adults with MDD [30,31].

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

Accelerated Intermittent Theta-Burst Stimulation for ... They found that active aiTBS was significantly more effective than sham stimulation for depressive symptoms, supporting the clinical efficacy of ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666915323001865

Accelerated intermittent theta-burst stimulation for the ... In six adolescents, accelerated iTBS was well-tolerated and in most cases, was followed by rapid antidepressant effects. These findings support the safe, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up. Detailed ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... TBS interventions in children may have similar safety, tolerability, and feasibility as compared to adults. However, long-term, follow-up studies of TBS are ...