Phase I Trial of High-Density Theta Burst Stimulation (hdTBS)

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type

Interventional

Phase

Phase 1

Age range

22 years - 60 years

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

40 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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:

This is a multi-site study conducted at the Biomedical Research Center, National Institute on Drug Abuse Intramural Research Program in Baltimore, Maryland and Olin Neuropsychiatry Research Center in Hartford, Connecticut.

Participants will have 4 clinic visits over about 3 to 4 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 3 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 up to 9 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....

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Be 22-60 years of age.

--Justification: Many neural processes change with age, and these changes could introduce unwanted variability in behavior. In addition, the risk of difficult-to detect medical abnormalities such as silent cerebral infarcts increase with age. Children under the age of 22 are excluded from this study because safety of rTMS in children has not been studied. In addition, this study is more than minimal risk and presents no direct benefit.
* Ability and willingness to provide written informed consent.

--Justification: At NIH/NIDA, written informed consent must be obtained for this study per NIH policy and federal regulations. At pSites, written informed consent must be obtained per applicable local institutional policy and regulations and as described in the pSite addendum.
* Generally in good health.

• Justification: Many illnesses may alter neural functioning. These will be evaluated by the MAI and excluded as needed.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

-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.

• Justification: Stroke or head trauma can lower the seizure threshold, and are therefore contra indications for TMS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures.

-First-degree family history of any form of epilepsy with a potentially hereditary basis.
* Justification: First-degree family history of epilepsy with a hereditary component increases the risk of the participant having an undiagnosed condition that is associated with lowered seizure threshold.

-Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object in the body that precludes TMS intervention.
* Justification: Any metal around the head is a contraindication for TMS, as it involves exposure to a relatively strong magnetic field.

-Noise-induced hearing loss or tinnitus.
* Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by TMS equipment.

-Current use (any use in the past 4 weeks, chronic use within 6 past six months) of any investigational drug or of any medications with psychotropic, anti or pro-convulsive action.
* Justification: The use of certain medications or drugs can lower seizure threshold and is therefore contraindicated for TMS.

-Lifetime history of major depressive disorder, schizophrenia, bipolar disorder, mania, or hypomania.
* Justification: The population of interest here is a healthy control population with no psychiatric disorders. In participants with depression, bipolar disorder, mania or hypomania, there is a small chance that TMS can trigger (hypo)manic symptoms.

-Current use of nicotine (self-report, urine cotinine test and/ or CO consistent with smoker) or history of more than 20 cigarettes or 20 instances of nicotine use in lifetime or history of daily nicotine use.
* Justification: The population of interest here is a healthy control population with no substance use disorder and therefore a minimal nicotine exposure history in the control group is required.

-Current regular use of more than 2 cups of coffee or equivalent caffeine intake in the morning (not total daily intake).
* Justification: Excessive caffeine use can reduce seizure threshold and could potentially increase risk of TMS-induced seizure.

-Meet current DSM-5 criteria for any substance use disorder, or urine toxicology positive for any illicit substance inconsistent with history given.
* Justification: The population of interest is a healthy control population with no substance use disorder. Current use of illicit substances could lower seizure threshold and is therefore contraindicated for TMS.

-Have met DSM-5 criteria for any substance use disorder in the past.
* Justification: the population of interest is a healthy control population with no present or past substance use disorder.

-History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or any heart condition currently under medical care.
* Justifications: the risk of TMS for individuals with a heart condition is unknown.

-Pregnant individuals or individuals with reproductive potential who are sexually active and do not report using contraception.
* Justification: it is unknown whether TMS poses a risk to fetuses.

-Otherwise TMS incompatible or have participated in any noninvasive brain stimulation (NIBS) session in the past two weeks or a NIBS treatment course in the past 6 months.
* Justification: in order to limit exposure to TMS, we will not enroll participants who have received TMS less than two weeks ago.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Random assignment

Masking

Double masked

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (2)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

2 locations

Study team and timeline

Lead sponsor

National Institute on Drug Abuse (NIDA)

Study start

Nov 15, 2026 Estimated

Primary completion

Jan 13, 2028 Estimated

Study completion

Jan 13, 2028 Estimated

First posted

Mar 11, 2025 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts