Major Depressive DisorderPhase 2NCT05652465
Transcranial Magnetic Stimulation for Youth With Treatment-Resistant Major Depressive Disorder
A Phase 2 study testing Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS) in people with Major Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: Major depressive disorder (MDD) is one of the most impairing medical conditions in the world. Medication and some kinds of talk therapy are standard treatments for teens with MDD, but these do not work well for everyone. Transcranial magnetic stimulation (TMS) has been approved to treat MDD in adults. Read more about this study
- Who is it for?
- Ages 13 to 17 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2026to 25 Apr 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Ages 13-17 at the time of enrollment
- Provision of signed and dated informed consent/assent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Is considered in good health and able to fulfill all study requirements in a manner that will not adversely impact the integrity of the data, as determined by the PI after review, as applicable, of a detailed screening assessment consisting of psychiatric and medical history, mental status, physical examinations, and laboratory assessments. In some circumstances it may also be highly desirable to review medical records from healthcare providers for the 2 years prior to study enrollment, from hospitals, psychiatric facilities, and pharmacy records for the year prior to study enrollment.
- Youths meet DSM 5TR criteria for Major Depressive Disorder (MDD), with a current, ongoing episode of MDD being present.
- To enter the trial, patients must meet criteria for treatment resistance, defined in the prior study of Croarkin and coworkers as the failure to respond to adequate trials or failure to tolerate trials of at least two selective serotonin reuptake inhibitors and a trial of either cognitive behavioral therapy or Interpersonal Psychotherapy for Adolescents (IPT-A). However, to receive TMS, patients must meet criteria for a stricter definition of treatment resistance. They must fail to respond to three interventions; only subjects who received and failed all three interventions will be invited to enroll into the TMS study. This will be defined as at least 20 mg of fluoxetine, 20 mg of citalopram (or 10 mg escitalopram), and 150 mg of sertraline. One of these interventions will involve psychotherapy with either Interpersonal Psychotherapy for Adolescents (IPT-A) or cognitive behavioral therapy (CBT) for at least 12 weeks. Of note, these treatments either can be delivered in the community, as determined based on medical history, or they can be delivered as part of protocol 18-M-0037.
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- Subject agrees to a Safety/Suicide Risk Management Protocol, which is intended to reduce the reduce the risk of suicide during study participation.
- Subject is currently under the care of a licensed prescriber and agrees to return to that provider upon completion of the study. During study participation, patients may continue to meet with their providers in the community, if they wish.
- Subject agrees, by signing Authorization for the Release of Medical Information forms (NIH-527) and informing all current providers, to allow any and all forms of communication between the investigators/study staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within two years of study enrollment.
- The participant is currently enrolled in protocol 18-M-0037
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Meets diagnostic criteria of DSM-5TR for psychosis, bipolar disorder, more than mild Autism Spectrum Disorder, ongoing severe Eating Disorder, ongoing substance use disorder (excluding nicotine) within the past month
- In the opinion of the PI, has a current or past medical or neurological disease, condition, injury, or illness (i.e., hearing loss, increased intracranial pressure, structural brain lesion, or head trauma associated with neurological sequalae, loss of consciousness, or hospitalization) that may: (a) reduce or diminish the subject s ability to fulfill all of the study requirements; or (b) adversely affect the integrity of the data or the results of the study. This includes the need for routine use of any medication (except for contraceptive implants or oral contraceptives) for any reason.
- Pregnancy
- Personal history of epilepsy, seizure(s), seizure disorder, or answers Yes to any of the nine (9) questions from the epilepsy screening instrument developed by Ottman et al.
- Has a history of, or risk factors for (history of syncope/ presyncope related to noxious stimuli, anxiety, micturition, or posture) for neurocardiogenic syncope
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- Currently receiving medication(s) that may, or is known to, reduce the seizure threshold and which, in the opinion of the PI, poses a clinically significant risk of a TMS-induced seizure that outweighs the potential benefit(s) of study participation.
- Lifetime lack of response to an adequate trial of electroconvulsive therapy
- Prior treatment with adequate trial of TMS
- Vagus nerve stimulator implant or other device implants
- Presence of intracranial implants or any other metal object within or near the head; those who have permanent retainers or other dental implants in the mouth that produce artifacts that compromise the integrity of MRI/fMRI data will be excluded from participation in this study.
- Intellectual disability (clinically identified or IQ less than 70)
- Symptoms of depression are due to physiologic effects of a drug of abuse or to a medical or neurological condition, as determined by the PI, based on history of contemporaneous onset of the symptoms and the associated drug or medical or neurological condition.
- Current active suicidal ideation (i.e., presence of intent for engaging in suicidal behaviors with a plan to act on the ideation) as demonstrated by a YES response to questions 4, 5 or 6 on the Columbia-Suicide Severity Rating Scale (Screen Version - Recent). [Note: Youths with passive suicidal ideation and/or past active suicidal ideation are still eligible - Answer Yes to Questions 1, 2 or 3.]
- Participants with recent or current history of repeated self-harm or suicide attempts occurring in the context of interpersonal conflict.
- NIMH IRP Employees/staff and immediate family members of such staff will be excluded from the study per NIMH policy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: An Open Trial of Transcranial Magnetic Stimulation for Youth With Treatment-Resistant Major Depressive Disorder
Background:
Major depressive disorder (MDD) is one of the most impairing medical conditions in the world. Medication and some kinds of talk therapy are standard treatments for teens with MDD, but these do not work well for everyone. Transcranial magnetic stimulation (TMS) has been approved to treat MDD in adults. TMS might help adolescents, too.
Read more
Objective:
To test TMS combined with cognitive behavioral therapy (CBT) in teens with MDD.
Eligibility:
People aged 13 to 17 years with MDD that has not responded to treatment.
Design:
Participants will be screened. They will have a physical exam and psychiatric evaluation. They will have an MRI scan and a test of their heart function. They will enroll in 2 NIH protocols (01-M-0254 and 18-M-0037).
For 2 to 6 weeks, participants will have weekly CBT, a kind of talk therapy. They will taper off of their psychiatric medicines.
For 2 weeks, participants will come to the clinic every weekday. They will receive 3 or 4 sessions of TMS on each of those days. A wire coil will be held on their scalp. A brief electrical current in the coil creates a magnetic pulse that affects brain activity. They will receive 30 TMS pulses in 10-second bursts; these will be repeated 60 times in each 15-minute session. Participants may hear a click and feel a pulling sensation under the coil. They may feel their muscles twitch. Each day, they will have tests of concentration, thinking, and memory. Some may have a 3rd week of TMS.
Participants will remain in the study for 5 more weeks. They will begin taking their medications again.
Read the detailed description
Study Description:
This is a safety and pilot efficacy study of open, neuronavigated intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS) in medication-free youth with treatment-resistant major depression. The hypothesis is that intermittent theta burst TMS is a safe and potentially effective treatment for treatment-resistant major depression in adolescents.
Objectives:
The study has two objectives: 1) To evaluate safety, feasibility, and potential efficacy of iTBS in medication-free youth with the goal of supporting a future randomized controlled trial in youth with treatment-resistant major depression; 2) To assess changes in levels of psychiatric symptoms and brain imaging parameters after iTBS in youth with treatment-resistant major depression.
Endpoints:
Primary Endpoints:
Children s Depression Rating Scale (CDRS); rates of treatment completion and adverse events on standard rating scales
Secondary Endpoints:
- Clinical Global Impression Improvement Scale (CGI-I)
- Mood and Feelings Questionnaire (MFQ)
- Screen for Child Anxiety Related Disorders (SCARED)
- Resting state fMRI correlations across brain regions
- Task-based fMRI activation to cognitive conflict
- Fractional anisotropy on diffusion tensor imaging
- Neurochemicals assessed by magnetic resonance spectroscopy
- Conditions
- Major Depressive Disorder
- Being tested
- Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS)
- Keywords
- TMS, Emotion, Magnetic Resonance Imaging, Brain Stimulation, CBT
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS)Device
Device described in protocol
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | TMS Receives: Device: Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment completion rate
Rate of participants completing 20 or more iTBS sessions
Measured: End of protocol
Adverse event rate
Clinical rating on standardized scale
Measured: Continuous
Clinician Depression Rating Scale
Clinician-rated report
Measured: Weekly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start25 Apr 2026
- Primary completion25 Apr 2026
- Study completion25 Apr 2026
Why it stopped: Not able to enroll subjects for this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daniel S Pine, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05652465
- Sponsor's protocol ID
- 10000776
- Other IDs
- 000776-M
- Status last verified
- Apr 2026
- First submitted
- 14 Dec 2022
- Last updated
- 28 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The full dataset will be shared to the extent that it is allowable by the IRB and consent process.
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Trial of Transcranial Magnetic Stimulation for Youth With Treatment-Resistant Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05652465
- Acronym / sponsor ID
- 10000776
- Conditions
- Major Depressive Disorder
- Keywords
- TMS, Emotion, Magnetic Resonance Imaging, Brain Stimulation, CBT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not able to enroll subjects for this study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 25 Apr 2026 (actual)
- Primary completion
- 25 Apr 2026 (actual)
- Study completion
- 25 Apr 2026 (actual)
- First posted
- 15 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Major depressive disorder (MDD) is one of the most impairing medical conditions in the world. Medication and some kinds of talk therapy are standard treatments for teens with MDD, but these do not work well for everyone. Transcranial magnetic stimulation (TMS) has been approved to treat MDD in adults. TMS might help adolescents, too.
Objective:
To test TMS combined with cognitive behavioral therapy (CBT) in teens with MDD.
Eligibility:
People aged 13 to 17 years with MDD that has not responded to treatment.
Design:
Participants will be screened. They will have a physical exam and psychiatric evaluation. They will have an MRI scan and a test of their heart function. They will enroll in 2 NIH protocols (01-M-0254 and 18-M-0037).
For 2 to 6 weeks, participants will have weekly CBT, a kind of talk therapy. They will taper off of their psychiatric medicines.
For 2 weeks, participants will come to the clinic every weekday. They will receive 3 or 4 sessions of TMS on each of those days. A wire coil will be held on their scalp. A brief electrical current in the coil creates a magnetic pulse that affects brain activity. They will receive 30 TMS pulses in 10-second bursts; these will be repeated 60 times in each 15-minute session. Participants may hear a click and feel a pulling sensation under the coil. They may feel their muscles twitch. Each day, they will have tests of concentration, thinking, and memory. Some may have a 3rd week of TMS.
Participants will remain in the study for 5 more weeks. They will begin taking their medications again.
Detailed description
Study Description:
This is a safety and pilot efficacy study of open, neuronavigated intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS) in medication-free youth with treatment-resistant major depression. The hypothesis is that intermittent theta burst TMS is a safe and potentially effective treatment for treatment-resistant major depression in adolescents.
Objectives:
The study has two objectives: 1) To evaluate safety, feasibility, and potential efficacy of iTBS in medication-free youth with the goal of supporting a future randomized controlled trial in youth with treatment-resistant major depression; 2) To assess changes in levels of psychiatric symptoms and brain imaging parameters after iTBS in youth with treatment-resistant major depression.
Endpoints:
Primary Endpoints:
Children s Depression Rating Scale (CDRS); rates of treatment completion and adverse events on standard rating scales
Secondary Endpoints:
- Clinical Global Impression Improvement Scale (CGI-I)
- Mood and Feelings Questionnaire (MFQ)
- Screen for Child Anxiety Related Disorders (SCARED)
- Resting state fMRI correlations across brain regions
- Task-based fMRI activation to cognitive conflict
- Fractional anisotropy on diffusion tensor imaging
- Neurochemicals assessed by magnetic resonance spectroscopy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Device: Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS)TMS |
Who may qualify
- Ages
- 13 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
Key exclusion criteria (16 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Meets diagnostic criteria of DSM-5TR for psychosis, bipolar disorder, more than mild Autism Spectrum Disorder, ongoing severe Eating Disorder, ongoing substance use disorder (excluding nicotine) within the past month
- In the opinion of the PI, has a current or past medical or neurological disease, condition, injury, or illness (i.e., hearing loss, increased intracranial pressure, structural brain lesion, or head trauma associated with neurological sequalae, loss of consciousness, or hospitalization) that may: (a) reduce or diminish the subject s ability to fulfill all of the study requirements; or (b) adversely affect the integrity of the data or the results of the study. This includes the need for routine use of any medication (except for contraceptive implants or oral contraceptives) for any reason.
- Pregnancy
- Personal history of epilepsy, seizure(s), seizure disorder, or answers Yes to any of the nine (9) questions from the epilepsy screening instrument developed by Ottman et al.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS)Device described in protocol | Device | Active |
Primary outcome
Treatment completion rate
Time frame: End of protocol
Rate of participants completing 20 or more iTBS sessions
Adverse event rate
Time frame: Continuous
Clinical rating on standardized scale
Clinician Depression Rating Scale
Time frame: Weekly
Clinician-rated report
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The full dataset will be shared to the extent that it is allowable by the IRB and consent process.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel S Pine, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intermittent theta burst repetitive transcranial magnetic stimulation (iTBS) in people with Major Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment completion rate (time frame: End of protocol). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.