High-Density TBS for Healthy Adults

Overseen By Yihong Yang, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Psychotropic, Anti-convulsive, Pro-convulsive

Disqualifiers: Stroke, Epilepsy, Depression, Schizophrenia, others

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

Compensation: Varies

Number of Visits: 5

Duration: 4-5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new form of brain stimulation called high-density theta burst stimulation (hdTBS) to determine if it is more effective than standard theta burst stimulation (TBS). The researchers aim to compare the effects of hdTBS and TBS on brain activity in healthy adults. It targets individuals who are generally healthy and have no history of neurological conditions or certain mental health disorders. Participants will receive either real or sham (inactive) TBS treatments over several visits. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that participants do not use any medications with psychotropic (affecting the mind), anti-convulsive (preventing seizures), or pro-convulsive (causing seizures) action in the past 4 weeks or chronically in the past 6 months. If you are taking such medications, you may need to stop them to participate.

What prior data suggests that high-density TBS is safe for healthy adults?

Studies have shown that transcranial magnetic stimulation (TMS), including high-density theta burst stimulation (hdTBS), is generally safe. People often experience mild side effects, such as headaches and neck pain, which usually resolve on their own.

Research indicates that headaches occur in about 6.6% to 16.7% of people. Other side effects, like dry eyes and fatigue, are less common. The most serious risk is a seizure during treatment, but this is very rare.

Before using hdTBS in humans, animal tests suggested it might have strong effects on the brain. This indicates potential effectiveness, but human safety is still under careful study. The trial under consideration is one of the first steps to ensure hdTBS is safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about High-Density Theta Burst Stimulation (hdTBS) because it offers a unique approach to brain stimulation compared to traditional methods like repetitive Transcranial Magnetic Stimulation (rTMS). Unlike most treatments that use longer sessions, hdTBS delivers short, intense bursts of magnetic pulses, potentially making the therapy quicker and more efficient. This technique might enhance brain plasticity more effectively, offering a promising alternative for modulating brain activity with fewer side effects and shorter treatment times.

What evidence suggests that high-density TBS could be effective for healthy adults?

Research has shown that high-density theta burst stimulation (hdTBS) might outperform traditional theta burst stimulation (TBS) due to its unique delivery of magnetic pulses. In this trial, participants will receive various versions of active TBS (3-, 4-, and 5-pulse TBS) along with sham TBS to compare their effects. One study found that similar TBS treatments can boost brain activity for up to 60 minutes, suggesting potential enhancement of brain stimulation. The aim of hdTBS is to amplify this effect, potentially leading to better outcomes for conditions like depression. While current research primarily focuses on safety and initial brain response, hdTBS is expected to provide stronger and longer-lasting effects than traditional methods. ^{2 6 7 8 9}

Who Is on the Research Team?

Yihong Yang, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 22 to 60 who are willing to avoid drugs, alcohol, and limit caffeine intake before clinic visits. They'll participate in a study involving a new form of brain stimulation therapy over several weeks.

Inclusion Criteria

Ability and willingness to provide written informed consent

I am generally healthy.

I am between 22 and 60 years old.

Exclusion Criteria

Personal history of stroke, brain lesions, previous neurosurgery, any personal history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness lasting over 30 minutes or with sequela lasting longer than two days or other neurological condition deemed by the MAI to be likely to affect response to the TBS being delivered

A close family member has had migraines, epilepsy, or multiple sclerosis.

I have hearing loss or ringing in my ears due to loud noise.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Orientation

Participants are oriented to TBS and undergo initial setup with cap and earplugs

1 visit

1 visit (in-person)

Treatment

Participants receive either active TBS or sham TBS over 4 visits

4-5 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High-Density Theta Burst Stimulation (hdTBS)

Trial Overview

Researchers are testing high-density Theta Burst Stimulation (hdTBS) using the MagVenture MagPro TMS device. The goal is to see if hdTBS can affect brain activity more effectively than standard TBS in healthy individuals.

How Is the Trial Designed?

Group I: Active TBS (3-,4-, and 5-pulse TBS) Active Control 1 Intervention

Each participant will receive 3 active TBS (3-,4-, and 5-pulse TBS) and 1 sham TBS on 4 visits separated by at least 48 hours to minimize any potential accumulating effects from prior visits.

Group II: Sham TBS Placebo Group 1 Intervention

Each participant will receive 3 active TBS (3-,4-, and 5-pulse TBS) and 1 sham TBS on 4 visits separated by at least 48 hours to minimize any potential accumulating effects from prior visits.

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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 randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Continuous theta burst stimulation (cTBS) effectively inhibits synaptic transmission in the primary motor cortex for up to 1 hour, demonstrating its potential as a novel neuromodulation technique.

cTBS applied to the left motor cortex increases local GABA levels, indicating enhanced GABAergic activity, while not significantly affecting glutamate/glutamine levels, suggesting a specific mechanism of action for this stimulation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. Stagg, CJ., Wylezinska, M., Matthews, PM., 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]

Theta burst stimulation (TBS) has been shown to affect brain connectivity, with continuous TBS (cTBS) generally decreasing functional connectivity and intermittent TBS (iTBS) increasing it, aligning with the expected neuroplasticity effects of long-term depression (LTD) and long-term potentiation (LTP).

Task-related outcomes from TBS are more inconsistent, particularly when applied to the prefrontal cortex, suggesting that individual differences and methodological factors significantly influence the effectiveness and variability of TBS responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the neurobiological effects of theta-burst stimulation (TBS) as measured using functional magnetic resonance imaging (fMRI). Kirkovski, M., Donaldson, PH., Do, M., et al.[2023]

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High-Density TBS for Healthy Adults

What data supports the effectiveness of the treatment High-Density Theta Burst Stimulation (hdTBS) for healthy adults? Research shows that a similar treatment, ...

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The current study has two objectives: (1) to further enhance the hdTBS protocol by increasing the burst frequency to 100 Hz while maintaining a ...

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ITBS applied for 190 s significantly increases cortical excitability up to 60 min with a mean maximum potentiation of 35.54 ± 3.32%.

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The most serious acute risk is a seizure occurring at the time of treatment. Less serious, but more frequent side effects of rTMS include headache and neck pain ...

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A Systematic Review of the Safety and Tolerability of Theta ...

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This study examined the efficacy and safety of the personalized neuroimaging–guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function ...