iTBS for Healthy Individuals

(STEP-MC Trial)

Overseen By Dewi Clark, MHSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Psychotropic medications

Disqualifiers: Age, DSM-5 diagnosis, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how different types of brain stimulation can enhance brain plasticity, the brain's ability to change and adapt. Researchers are testing two types of non-invasive brain stimulation: compressed iTBS (Intermittent Theta-Burst Stimulation) and spaced iTBS, to determine which is more effective in healthy, right-handed individuals. Participants will undergo brain activity measurement through harmless magnetic pulses to detect changes in brain plasticity. Ideal candidates have no history of mental disorders and are not taking medications for mental health. As an unphased trial, this study allows participants to contribute to groundbreaking research in brain plasticity.

Will I have to stop taking my current medications?

If you are currently using any psychotropic medications (like anti-depressants or anti-convulsants), you will need to stop taking them to participate in this trial.

What prior data suggests that this iTBS protocol is safe for healthy individuals?

Studies have shown that intermittent theta-burst stimulation (iTBS) is generally safe, including both the compressed (iTBS-c) and spaced (iTBS-s) methods. Research indicates that iTBS-c effectively treats depression and is well-tolerated, with mild side effects in about 5% of people. Evidence supports the safety and tolerability of iTBS-s when used once or twice a day. These findings suggest that both types of iTBS are well-tolerated, with a low risk of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the iTBS (intermittent theta burst stimulation) techniques being tested because they could offer more efficient brain stimulation methods for cognitive enhancement in healthy individuals. Unlike standard repetitive transcranial magnetic stimulation (rTMS) protocols, which often require longer sessions, the compressed iTBS delivers similar benefits in a shorter time frame, making it more convenient. Meanwhile, the spaced iTBS approach explores whether spreading out the stimulation sessions can lead to more sustained cognitive benefits. This trial is unique as it investigates not just the immediacy of results, but also the potential for long-lasting cognitive improvements with these innovative protocols.

What evidence suggests that this trial's treatments could be effective for improving brain plasticity?

Research has shown that intermittent theta-burst stimulation (iTBS) can help the brain reorganize and form new connections, a process known as brain plasticity. This trial will administer different types of iTBS, including compressed iTBS (iTBS-c) and spaced iTBS (iTBS-s), to examine their effects on brain activity and plasticity. Studies have found that iTBS-c effectively treats depression by strengthening brain connections. A review of multiple studies found that iTBS can improve thinking skills in healthy adults, highlighting its potential to enhance brain plasticity. Overall, both iTBS-c and iTBS-s support brain changes and growth, with research showing promise in improving brain function. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy, right-handed individuals aged 18 to 50 who are interested in contributing to research on brain plasticity. Participants should be able to attend five study visits over three months.

Inclusion Criteria

Right handedness, assessed using the Edinburgh Handedness Inventory (EHI)

Sufficiently proficient in English to complete the required study assessments, as per investigator judgement

Willingness to comply with all study procedures

Exclusion Criteria

Contraindications to transcranial magnetic stimulation (TMS), as per investigator judgment

Lifetime history of any Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis, assessed using the Structured Clinical Interview for DSM-5 (SCID-5), except simple phobias

I am either 17 years old or younger, or older than 51.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Calibration

Calibration iTBS session to assess tolerability of brain stimulation

1 week

1 visit (in-person)

Treatment

Participants undergo three experimental iTBS sessions (iTBS-s, iTBS-c, and iTBS-sh) in a randomized order, each separated by at least 72 hours. The study team stimulates the motor cortex and records muscle activity to measure changes in brain plasticity.

2 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Compressed iTBS
• Sham iTBS
• Spaced iTBS

Trial Overview The trial tests the effects of different iTBS protocols on brain plasticity. It compares spaced iTBS (iTBS-s), compressed iTBS (iTBS-c), and sham iTBS (iTBS-sh) using non-invasive magnetic pulses applied to the motor cortex.

How Is the Trial Designed?

Group I: Spaced iTBS Experimental Treatment 1 Intervention

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-s condition in a randomized order during Visits 3 to 5. iTBS-s is the experimental study intervention.

Group II: Compressed iTBS Active Control 1 Intervention

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-c condition in a randomized order during Visits 3 to 5. iTBS-c is the active comparator.

Group III: Sham iTBS Placebo Group 1 Intervention

After completing Visits 1-2 (Screening and Calibration), participants will undergo the iTBS-sh condition in a randomized order during Visits 3 to 5. iTBS-sh is the sham comparator.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

Intermittent theta-burst stimulation (iTBS) may enhance cognitive function compared to control conditions, but results vary widely across studies due to methodological differences and small sample sizes (often less than 30 participants).

The meta-analysis highlights the need for standardization in iTBS application, as factors like stimulation location significantly affect outcomes, while the type of cognitive task does not contribute to variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of the efficacy of intermittent theta burst stimulation (iTBS) on cognitive enhancement. Pabst, A., Proksch, S., Médé, B., et al.[2022]

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 of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

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 36 multiple sclerosis patients, intermittent theta burst stimulation (iTBS) significantly improved manual dexterity, as shown by faster completion times in the nine-hole peg test and increased performance in the Box and Block Test.

However, iTBS did not have a significant impact on hand motor imagery abilities, indicating that while it can enhance physical tasks, it may not affect cognitive aspects of motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Intermittent Theta Burst Stimulation on Manual Dexterity and Motor Imagery in Patients with Multiple Sclerosis: A Quasi-Experimental Controlled Study. Azin, M., Zangiabadi, N., Iranmanesh, F., et al.[2020]

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) 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]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

In a study involving 12 subacute stroke patients, prolonged transcranial magnetic stimulation (iTBS1200) was found to be safe and well-tolerated, with no significant adverse effects reported.

Patients receiving iTBS1200 showed measurable improvements in stroke severity and upper extremity function shortly after treatment and at 60 days post-stroke, suggesting potential benefits that warrant further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. Hsu, YF., Huang, YZ., Lin, YY., et al.[2022]

In a study involving 34 healthy female participants, the effectiveness of intermittent theta burst stimulation (iTBS) on reducing stress was linked to the resting-state functional connectivity (rsFC) between the left dorsolateral prefrontal cortex (DLPFC) and the caudal anterior cingulate cortex (ACC).

Participants with a stronger negative correlation in rsFC experienced a greater reduction in stress sensitivity after active iTBS, suggesting that individual brain connectivity patterns could help tailor and improve the treatment's effectiveness for stress-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual resting-state frontocingular functional connectivity predicts the intermittent theta burst stimulation response to stress in healthy female volunteers. de Wandel, L., Pulopulos, MM., Labanauskas, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... This randomized clinical trial assesses the effectiveness of accelerated intermittent theta-burst stimulation for depressive symptom reduction

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725000023

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression This trial will compare the effects of the compressed iTBS (iTBS-c) protocol, which is commonly used to treat depression, and the spaced ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1244289/full

Efficacy and safety of intermittent theta burst stimulation ... A recent meta-analysis found that iTBS shown a positive effect in enhancing neurocognitive function in healthy adults (49). The findings ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423820/

Efficacy and safety of intermittent theta burst stimulation ... A recent meta-analysis found that iTBS shown a positive effect in enhancing neurocognitive function in healthy adults (49). The findings ...

7. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT04684706

Compressed Intermittent Theta Burst Stimulation Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe treatment for TRD, yet the standard clinical technique for using it as treatment ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... Overall, iTBS is considered an effective, safe and tolerable treatment for depression (Stultz et al., 2020) (Chu et al., 2021). The differences ...

9. withpower.com withpower.com/trial/phase-healthy-control-subjects-10-2024-1a58b

iTBS for Healthy Individuals (STEP-MC Trial) Research shows that intermittent theta burst stimulation (iTBS) is generally safe, with most side effects being mild and occurring in about 5% of people.