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

35 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment High-Density Theta Burst Stimulation (hdTBS) for healthy adults?

Research shows that a similar treatment, intermittent theta burst stimulation (iTBS), can improve cognitive speed and increase brain connectivity in healthy adults. It has also shown promise in treating symptoms of depression, suggesting potential benefits for brain function. ^{1 2 3 4 5}

Is high-density theta burst stimulation (hdTBS) safe for humans?

Research on theta burst stimulation (TBS), including studies on healthy adults and those with neurological conditions, suggests it is generally safe, though individual responses can vary. Some studies report changes in brain activity, but no major safety concerns have been consistently identified. ^{5 6 7 8 9}

How is High-Density Theta Burst Stimulation (hdTBS) different from other treatments?

High-Density Theta Burst Stimulation (hdTBS) is unique because it uses a high-definition electrical stimulation approach to modulate brain activity, which may offer better precision and efficacy compared to traditional repetitive transcranial magnetic stimulation (rTMS) methods. This treatment is designed to enhance or suppress brain activity more effectively than conventional techniques. ^{1 6 8 10 11}

What is the purpose of this trial?

Background: Transcranial magnetic stimulation (TMS) uses magnetic pulses to affect brain activity. A type of TMS called theta burst stimulation (TBS) is approved to treat people with major depression. Researchers have developed a new form of TBS called high-density TBS (hdTBS). They hope hdTBS will work better than TBS. But first they need to test the new treatment in healthy adults. Objective: To test hdTBS in healthy adults. Also, to compare the aftereffects of hdTBS and TBS. Eligibility: Healthy adults aged 22 to 60 years. Design: Participants will have 5 clinic visits over 4 to 5 weeks. They must abstain from drugs and alcohol and limit caffeine before visits. At their first visit, participants will be oriented to TBS. They will wear a cap and earplugs. A device with round coils will be placed near their head. When a brief electric current passes through the coil, it generates a magnetic pulse that stimulates the brain. Participants may feel a pulling sensation on the skin under the coil. Their fingers may move involuntarily. At their next 4 visits, participants will receive either TBS or sham TBS. A sham TBS uses a low magnetic field to minimize the effects of the treatment. Participants will have 3 to 6 electrodes placed on 1 arm. These electrodes will measure the electrical activity in their muscles. Each TBS session will be videotaped. At every visit, participants will answer questions about their health, including substance use. They will perform 2 tasks to test their thinking skills. They will perform a test on a computer to test their reaction time.

Research Team

Yihong Yang, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

2. Netherlands 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. [2021]

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

Theta Burst Stimulation Enhances Connectivity of the Dorsal Attention Network in Young Healthy Subjects: An Exploratory Study. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of theta burst stimulation over the human sensorimotor cortex on motor and somatosensory evoked potentials. [2008]

5. Germany 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). [2023]

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

Neural effects of continuous theta-burst stimulation in macaque parietal neurons. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Theta-burst stimulation as a therapeutic tool in neurological pathology: a systematic review. [2023]

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

Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Pattern-specific role of the current orientation used to deliver Theta Burst Stimulation. [2022]

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

Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation. [2022]

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

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study. [2022]