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

Launched by NATIONAL INSTITUTE ON DRUG ABUSE (NIDA) · Mar 10, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new type of brain stimulation called high-density theta burst stimulation (hdTBS) in healthy adults. Researchers want to see if hdTBS is more effective than an existing treatment known as theta burst stimulation (TBS), which is already used to help people with depression. The trial is open to healthy adults between the ages of 22 and 60 who meet certain health criteria. Participants will need to be in good health, provide written consent, and avoid using drugs, alcohol, or excessive caffeine before their visits.

During the trial, participants will visit the clinic five times over four to five weeks. At the first visit, they will learn more about the procedure and will have a device placed near their head that sends magnetic pulses to stimulate their brain. They may feel a slight pulling sensation. In the following visits, participants will receive either the actual hdTBS treatment or a low-intensity version called sham TBS, which is designed to have minimal effects. Throughout the trial, participants will answer questions about their health and perform tests to check their thinking skills and reaction times. This study is important in understanding how hdTBS works and whether it could be a better treatment option in the future.

Gender

ALL

Eligibility criteria

• * 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: Written informed consent must be obtained for this study per NIH policy and federal regulations.
• • 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.