Accelerated Intermittent Theta Burst in Treatment-Naive Adolescents (paiTBS-KID)

August 18, 2026 updated by: Sean O'Sullivan, University of Texas at Austin

Investigating a Truncated Version of paiTBS in Treatment-Naive Adolescents With Depression: An Open-Label Acceptability Trial

This is a single-site open-label clinical trial of fMRI-guided accelerated intermittent theta burst stimulation. The goal of this clinical trial is to learn if a new form of transcranial magnetic stimulation (TMS)-known generally as accelerated intermittent theta burst stimulation (aiTBS)-is effective as a first-line therapy in treating adolescents aged 13-20 years-old in their first episode of depression who have not undergone a full course of depression treatment prior to starting the trial and who remain antidepressant-free throughout the trial.

The main questions this trial aims to answer are:

  • Does aiTBS relieve symptoms of depression as a first-line therapy in adolescents?
  • Is aiTBS a feasible option as a first-line treatment for adolescent depression?

Researchers will measure the depression symptoms in adolescent participants before and after aiTBS. Parents of the adolescent participant will also participate in the study providing information about their experience and preference for TMS as a first-line treatment.

Adolescent participants will:

  • Remain antidepressant-free throughout the study period of 6-7 weeks.
  • Receive an fMRI of their head for precision targeting
  • Receive 5 days of aiTBS

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This single-site open-label clinical trial aims to test the safety and efficacy of precision accelerated intermittent theta burst stimulation (paiTBS) in treatment-naive adolescents with major depressive disorder (MDD) who remain antidepressant-free throughout the treatment. The paiTBS protocol, or a truncated version (5 or 10 applications per day to a customized target within the left dorsolateral prefrontal cortex [L-DLPFC] identified with fMRI for five consecutive days), in combination with MNS software will be delivered to each adolescent participant. Changes in depressive symptoms will be measured at baseline and two follow up visits. Additionally, parents and adolescents will answer questions regarding their preference for paiTBS as a first-line treatment option for MDD.

The hypothesis is that adolescent participants receiving paiTBS or the truncated version will demonstrate similar response and remission rates that are comparable to aiTBS trials in adults (80-90%) as measured by the Childhood Depression Rating Scale (CDRS) and Hamilton Depression Rating Scale.

The primary objective of this study is to determine the efficacy of active paiTBS in reducing symptoms of depression as measured by the CDRS at the one-month follow up time point.

The study will enroll approximately 40 participants and employ a two-arm design with 20 participants per arm. The target population is adolescents of all genders and ethnicities who are between 13 and 20 years of age with a diagnosis of MDD experiencing their first major depressive episode who have not received a full course of prior treatment and who are otherwise in good general health. Participants must be without contraindications to Magnetic Resonance Imaging (MRI) or transcranial magnetic stimulation (TMS) and must be able to attend all study visits.

This study will deliver paiTBS via a MagPro X100 edition (MagVenture, Skovlunde, Denmark) TMS device equipped with a Cool-B65 A/P coil. The stimulation paradigm consists of 5 or 10 daily sessions (25 or 50 total over 5-days) of paiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or Female, between the ages of 13 and 20 at the time of screening.
  2. Able to read, understand, and provide written, dated assent and/or consent prior to screening. Proficiency in English sufficient to complete questionnaires and follow instructions during aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
  3. Diagnosed with Major Depressive Disorder (MDD) with a current Major Depressive Episode (MDE), according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
  4. No prior major depressive episodes (MDEs) as determined by MINI-KID
  5. CDRS-R score of ≥40 at screening (Visit 1).
  6. Treatment-naive as determined by the ATHF (no adequate antidepressant trials prior to screening defined as fewer than 12 weeks of antidepressant medication in the past 2 years and fewer than 10 psychotherapy sessions for depression in the past year; willingness to taper medications and stop psychotherapy if recently started and within the window defined above.)
  7. TMS naive.
  8. Access to ongoing psychiatric care before and after completion of the study.
  9. In good general health, as evidenced by medical history.
  10. Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

  1. Pregnancy
  2. High-risk for suicide or active suicidal ideation as determined by clinical interview
  3. The presence or diagnosis of prominent anxiety disorder, or dysthymia (>4 on SAPAS; >16 on GAD-7)
  4. Current severe insomnia (must sleep a minimum of 5 hours each night before stimulation)
  5. Current mania or psychosis
  6. Bipolar Affective Disorder and/or primary psychotic disorders.
  7. Autism Spectrum disorder or Intellectual Disability
  8. A diagnosis of obsessive-compulsive disorder (OCD)
  9. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal.
  10. Urine screening test positive for illicit substances.
  11. Any history of ECT (greater than 8 sessions) without meeting responder criteria
  12. Recent (during the current depressive episode) or concurrent use of a rapid acting antidepressant agent (i.e., ketamine or a course of ECT).
  13. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, unexpected seizure/epilepsy disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma.
  14. Untreated or insufficiently treated endocrine disorder.
  15. Contraindications to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
  16. Contraindications to MRI (ferromagnetic metal in their body).
  17. Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
  18. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
  19. Treatment with another investigational drug or other intervention within the study period.
  20. Any other condition deemed by the PI to interfere with the study or increase risk to the participant.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Full-Dose paiTBS
10 daily sessions (50 total over 5-days) of paiTBS stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark)
10 daily sessions (50 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark)
5 daily sessions (25 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
Experimental: Half-Dose paiTBS
5 daily sessions (25 total over 5-days) of paiTBS stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark)
10 daily sessions (50 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark)
5 daily sessions (25 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Childhood Depression Rating Scale-Revised (CDRS-R) Remission Rates
Time Frame: Baseline, One Month Follow Up Visit

Seventeen item diagnostic questionnaire which psychiatrists use to measure the severity of depressive symptoms in adolescents with depression.

The investigators will assess the difference in CDRS-R scores/remission rates between the full-dose paiTBS group compared to those who received half-dose paiTBS at the one-month follow up visit.
Baseline, One Month Follow Up Visit
Childhood Depression Rating Scale-Revised (CDRS-R) Remission Rates
Time Frame: Baseline, One Month Follow Up Visit
The investigators will assess the difference in CDRS-R response rates (reduction >50% of CDRS-R baseline score) between the full-dose aiTBS group compared to those who received half-dose aiTBS.
Baseline, One Month Follow Up Visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas at Austin

Collaborators

Magnus Medical

Investigators

  • Principal Investigator: Sean J O'Sullivan, M.D., Ph. D., University of Texas at Austin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

July 22, 2024

First Submitted That Met QC Criteria

July 22, 2024

First Posted (Actual)

July 26, 2024

Study Record Updates

Last Update Posted (Actual)

August 19, 2026

Last Update Submitted That Met QC Criteria

August 18, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NECMHR01-FY24-032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe