ClinicalTrials.gg
Not yet recruitingNCT06868914Updated Nov 10, 2026

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

A Phase 1 interventional study of TMS (MagVenture MagPro 100 with MagOption) in Healthy Volunteers, sponsored by National Institute on Drug Abuse (NIDA). Not yet recruiting at 2 sites in United States. Open to participants aged 22 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-10.

Sponsored by National Institute on Drug Abuse (NIDA) · Phase 1, Interventional, and Basic science

Updated Nov 10, 2026Start date movedStudy contact changedGo to Updates ↓
Phase
Phase 1
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
22 Years to 60 Years
Sex
All
01

Study summary

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....

Read the detailed description

Study Description:

This study is intended to test the safety and potential efficacy of the highdensity theta burst stimulation (hdTBS) paradigm. We hypothesize that hdTBS i) can be safely administered to normal healthy human subjects, and ii) can produce stronger and longer-lasting after-effects than the conventional FDA-approved TBS paradigm.

Objectives:

Primary Objective:

To determine whether hdTBS at the power level of 60% and 80% resting motor threshold can be safely administered to normal healthy human participants.

Secondary Objective:

To determine whether hdTBS produces stronger and longer-lasting after-effects than the conventional, FDA-approved TBS protocol. Here "after-effects" are defined as alterations in cortical excitability after TMS administration, which can be quantitatively assessed by measuring motor-evoked potential (MEP) before and after an acute session of TMS on the primary motor cortex. Changes in the characteristics and durations of the MEP signal relative to pre-TMS baseline reflect neuromodulation effects of the TMS session.

Endpoints:

Primary Endpoint:

Clinically significant adverse events as collected on the Noninvasive Brain Stimulation (NIBS) monitoring questionnaire and evaluated by the MAI in combination with the serious adverse event reports.

Secondary Endpoints:

20 complete datasets at the 80% RMT hdTBS dose that are evaluable for after-effects of hdTBS.

02

Conditions studied

  • Healthy Volunteers

Keywords

  • Substance Use Disorders (SUDs)
  • Transcranial Magnetic Stimulation (TMS)
  • Theta Burst Stimulation (TBS)
  • High-density Theta Burst Stimulation (hdTBS)
03

In context

Substance-Related Disorders

2,238 studies on the registry are indexed under Substance-Related Disorders; 409 are open to participants now.

This study's planned enrollment of 40 is below the median of 108 across 1,840 interventional studies indexed under Substance-Related Disorders.

Browse Substance-Related Disorders studies →

Lead sponsor

National Institute on Drug Abuse (NIDA) is the lead sponsor of 393 studies on the registry; 19 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 6 (43%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
22 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 .

    --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

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 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 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 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 , 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 who are sexually active and do not report using .

  • 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.
Terms in these criteria, in plain language(7)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

DSM diagnostic criteria

The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Single group
Masking
Double (Participant, Investigator)
Enrollment
40 participants (estimated)

Study arms

  • Active comparator
    Active TBS (3- and 5-pulse TBS)

    Each participant will receive 2 active TBS (3- and 5-pulse TBS) and 1 sham TBS on 3 visits separated by at least 48 hours to minimize any potential accumulating effects from prior visits.

    Device: TMS (MagVenture MagPro 100 with MagOption)

  • Sham comparator
    Sham TBS

    Each participant will receive 2 active TBS (3- and 5-pulse TBS) and 1 sham TBS on 3 visits separated by at least 48 hours to minimize any potential accumulating effects from prior visits.

    Device: TMS (MagVenture MagPro 100 with MagOption)

Interventions

  • DeviceTMS (MagVenture MagPro 100 with MagOption)

    TMS will be applied using the MagVenture MagPro 100 with MagOption (MagVenture Inc, Alpharetta, GA) stimulator with a figure-of-8 TMS coil. Each subject will receive 2 active TBS (3- and 5-pulse TBS) and 1 sham TBS on 3 visits separated by at least 48 hours.

06

What researchers measure

Primary outcomes

  1. Clinically significant adverse events as collected on the Noninvasive Brain Stimulation (NIBS) monitoring questionnaire and evaluated by the MAI in combination with the serious adverse event reports.

    As a phase I trial, 25 participants are a reasonable sample size for a preliminary assessment of the safety profile of the hdTBS paradigm.

    Time frame: about 3-4 weeks

Secondary outcomes

  1. 20 complete datasets at the 80% RMT hdTBS dose that are evaluable for after-effects of hdTBS.

    20 complete datasets should give sufficient power to detect an effect. hdTBS produces stronger and longer lasting after-effects sets a solid foundation for future study in patients to investigate the efficacy of the new TMS paradigm.

    Time frame: about 3-4 weeks

07

Study locations

2 sites
08

References and documents

Individual participant data

Plan to share: Yes — We share information with researchers outside the NIH in two ways. Most commonly, we have specific partnerships with other researchers. Also, we may put data into one or more scientific databases, where it is stored along with information from other studies. Researchers can then study the information combined from many studies to learn even more about health and disease. We will share some protocol data with our scientific research partners inside or outside the NIH. Research partners outside the NIH sign an agreement with the NIH to share data. This agreement indicates the type of data that can be shared and what can be done with those data.@@@Additionally, de-identified data may be shared with properly administered databases and/or with collaborators with whom proper data sharing agreements are in place, after consultation with and approval from the NIDA-IRP Scientific Director.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code

Time frame: Data will be made available at the time of publication and as long as the archive is online or for a minimum of 5 years after publication in the event it must be moved to new hosting archives.

Access criteria: We may put data into one or more scientific databases, where it is stored along with information from other studies. We will share some protocol data with our scientific research partners inside or outside the NIH. Research partners outside the NIH sign an agreement with the NIH to share data. This agreement indicates the type of data that can be shared and what can be done with those data.@@@Additionally, de-identified data may be shared with properly administered databases and/or with collaborators with whom proper data sharing agreements are in place, after consultation with and approval from the NIDA-IRP Scientific Director. Data shared with NIH investigators outside of NIDA, unless otherwise stated, would be sent by NIDA as de-identified data via secure email, encryption or secured ftp. The code to those data will not be shared.

No publications or documents are linked to this record.

09

Timeline

32 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedDate before it movedWhere the date was before it movedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Nov 2026; primary completion for Jan 2028, 13 months later.

Of 30 non-industry phase 1 interventional studies under Substance-Related Disorders, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 46. This study's planned 13 months is below that.

Counting every sponsor, half of 54 studies reached it within 12 months; a quarter within 4 and three quarters within 33.

Start moved 32 times since we started tracking on Sep 25, 2026: Sep 2026 → Nov 2026, last on Nov 10, 2026.

Earlier changes are on the record history on ClinicalTrials.gov ↗

How these figures are worked out, and which studies are left out of them.

Registered
Mar 10, 2025
First posted
Mar 11, 2025
StartEst.
Nov 15, 2026was Sep 2026
Primary completionEst.
Jan 13, 2028
CompletionEst.
Jan 13, 2028
Last update
Nov 10, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Start date
Sep 29, 2026→Nov 15, 2026
moved 32 times, Sep 25, 2026 – Nov 10, 2026
Contact
Study contact changed: added k•••@nih.gov · •••5287. See the current contact
Sep 25, 2026
Site contacts
Changed at 1 site. See the sites
Show the site
  • National Institute on Drug Abuse · Baltimore, United StatesContact k•••@nih.gov · •••5287→k•••@nih.gov · •••5287
Sep 29, 2026
Show all 32 updates
  1. Nov 10, 2026
    Start date Nov 12, 2026→Nov 15, 2026
  2. Nov 9, 2026
    Start date Nov 11, 2026→Nov 12, 2026
  3. Nov 6, 2026
    Start date Nov 10, 2026→Nov 11, 2026
  4. Nov 5, 2026
    Start date Nov 9, 2026→Nov 10, 2026
  5. Nov 4, 2026
    Start date Nov 8, 2026→Nov 9, 2026
  6. Nov 3, 2026
    Start date Nov 5, 2026→Nov 8, 2026
  7. Nov 2, 2026
    Start date Nov 4, 2026→Nov 5, 2026
  8. Oct 30, 2026
    Start date Nov 3, 2026→Nov 4, 2026
  9. Oct 29, 2026
    Start date Nov 2, 2026→Nov 3, 2026
  10. Oct 28, 2026
    Start date Nov 1, 2026→Nov 2, 2026
  11. Oct 27, 2026
    Start date Oct 29, 2026→Nov 1, 2026
  12. Oct 26, 2026
    Start date Oct 28, 2026→Oct 29, 2026
  13. Oct 23, 2026
    Start date Oct 27, 2026→Oct 28, 2026
  14. Oct 22, 2026
    Start date Oct 26, 2026→Oct 27, 2026
  15. Oct 21, 2026
    Start date Oct 25, 2026→Oct 26, 2026
  16. Oct 20, 2026
    Start date Oct 22, 2026→Oct 25, 2026
  17. Oct 19, 2026
    Start date Oct 21, 2026→Oct 22, 2026
  18. Oct 16, 2026
    Start date Oct 20, 2026→Oct 21, 2026
  19. Oct 15, 2026
    Start date Oct 19, 2026→Oct 20, 2026
  20. Oct 14, 2026
    Start date Oct 18, 2026→Oct 19, 2026
  21. Oct 13, 2026
    Start date Oct 14, 2026→Oct 18, 2026
  22. Oct 9, 2026
    Start date Oct 13, 2026→Oct 14, 2026
  23. Oct 8, 2026
    Start date Oct 12, 2026→Oct 13, 2026
  24. Oct 7, 2026
    Start date Oct 11, 2026→Oct 12, 2026
  25. Oct 6, 2026
    Start date Oct 8, 2026→Oct 11, 2026
  26. Oct 5, 2026
    Start date Oct 7, 2026→Oct 8, 2026
  27. Oct 2, 2026
    Start date Oct 6, 2026→Oct 7, 2026
  28. Oct 1, 2026
    Start date Oct 5, 2026→Oct 6, 2026
  29. Sep 30, 2026
    Start date Oct 4, 2026→Oct 5, 2026
  30. Sep 29, 2026
    Start date Oct 1, 2026→Oct 4, 2026
    Site contacts Changed at 1 site. See the sites
    Show the site
    • National Institute on Drug Abuse · Baltimore, United StatesContact k•••@nih.gov · •••5287→k•••@nih.gov · •••5287
  31. Sep 28, 2026
    Start date Sep 30, 2026→Oct 1, 2026
  32. Sep 25, 2026
    Start date Sep 29, 2026→Sep 30, 2026
    Contact Study contact changed: added k•••@nih.gov · •••5287. See the current contact

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06868914
Responsible party
Sponsor
First posted
Mar 11, 2025
Start date
Nov 15, 2026 (estimated)
Primary completion
Jan 13, 2028 (estimated)
Completion
Jan 13, 2028 (estimated)
Last update
Nov 10, 2026

Study contacts

Kimberly C Slater
Contact
kmodo@nih.gov
(667) 312-5287
Yihong Yang, Ph.D.
Contact
yihongyang@intra.nida.nih.gov
(667) 312-5364
Yihong Yang, Ph.D.
principal investigator · National Institute on Drug Abuse (NIDA)

Oversight

FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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