Feasibility, Safety, and Preliminary Clinical Efficacy of Magnetic Resonance Imaging-guided Repetitive Transcranial Magnetic Stimulation (rTMS) in Adolescents With Depression: A Randomized, Double-Blind, Controlled Pilot Study

NCT07185438 | Recruiting DMC

• 1 other identifier: 1stChongqingCQMU___ZXY
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to assess the feasibility, safety, acceptability, and preliminary efficacy trends of a Magnetic Resonance Imaging-guided Repetitive Transcranial Magnetic Stimulation (rTMS) intervention for adolescent depression through a pilot clinical trial. The findings will inform the design and optimization of subsequent formal randomized controlled trials, providing essential evidence for their execution.

Conditions

Depression - Major Depressive Disorder

Outcome Measures

Primary Outcomes (5)

• Recruitment Feasibility (Number of Participants Enrolled)

  The total number of participants successfully enrolled in this study will be recorded to assess recruitment feasibility. The goal is to recruit 45 participants (15 in each of the three groups) over a 2-year period.

  2 years

• Intervention adherence (number of participants who completed the full 20 treatment sessions)

  This outcome measure will assess participants' adherence to the 20 sessions of transcranial magnetic stimulation. Adherence is defined as completing all 20 sessions. Adherence is calculated by dividing the number of participants who met this criterion by the total number of participants.

  Throughout the entire course of treatment (up to 1 month)

• Retention Rate (Number of Participants Remaining at 6-Month Follow-up)

  This outcome measure will assess the proportion of participants still enrolled in the study at the 6-month follow-up assessment. Retention rate is calculated as the number of participants who completed the 6-month assessment divided by the number of participants enrolled at baseline.

  Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Response rate and remission rate of depressive symptoms

  Preliminary clinical efficacy will be assessed by change in the Children's Depression Rating Scale-Revised (CDRS-R) total score from baseline. CDRS-R is a clinician-rated scale used to assess the severity of depressive symptoms in children and adolescents. It consists of 17 items, and the total score ranges from 17 to 113. Higher scores indicate more severe depressive symptoms. Changes in CDRS-R total score from baseline will be assessed at the end of treatment and at follow-up visits. Response rate of depressive symptoms will be defined as a ≥50% reduction in CDRS-R total score from baseline, and remission rate of depressive symptoms will be defined as a CDRS-R total score ≤28.

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Incidence of Adverse Events and Serious Adverse Events

  Adverse events, abbreviated as AEs, and serious adverse events, abbreviated as SAEs, will be assessed to evaluate the safety and tolerability of the intervention. An AE is defined as any unfavorable medical occurrence in a participant during the study period, regardless of whether it is considered related to the intervention. An SAE is defined as any adverse event that results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is otherwise considered medically significant. The number and proportion of participants experiencing at least one AE or SAE will be recorded throughout the study period. The severity, outcome, and relationship to the intervention will also be documented.

  Throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

Secondary Outcomes (9)

• Change in BDI-II (Beck Depression Inventory-II) scores from baseline

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Change in HAMA score from baseline

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale)

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

• Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline

  Baseline, throughout the entire course of treatment (up to 1 month) and follow-up (up to 6 months)

Study Arms (3)

Experimental target rTMS treatment group

EXPERIMENTAL

Participants will undergo MRI-guided identification of the voxel in the left dorsolateral prefrontal cortex (DLPFC) that is most negatively correlated with the functional connectivity of the subgenual anterior cingulate cortex (sgACC) as the stimulation site. Repetitive transcranial magnetic stimulation (rTMS) (10 Hz, 120% RMT) will be administered using the Blackdolphin TMS Robot device (model SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 20 sessions over 4 weeks (treatment administered on weekdays).

Device: Experimental target rTMS treatment

Conventional target rTMS treatment group

EXPERIMENTAL

Participants will receive MRI-guided stimulation at the left DLPFC location. Repetitive transcranial magnetic stimulation (rTMS) (10 Hz, 120% RMT) will be administered using the Blackdolphin TMS Robot device (model SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 20 sessions over 4 weeks (treatment administered on weekdays).

Device: Conventional target rTMS treatment

Sham stimulation treatment group

SHAM COMPARATOR

Participants will receive a sham stimulation treatment designed to simulate the rTMS procedure without generating an effective magnetic field output. The intervention will use a dedicated sham stimulation coil, which is identical in appearance, operation, and stimulation protocol to the experimental group. This coil is designed to maintain the same auditory and tactile sensations as the active stimulation but is equipped with an electromagnetic shielding structure or an internal reverse coil arrangement to effectively prevent magnetic flux from penetrating the skull, ensuring no actual neuromodulatory effects.

Device: Sham stimulation treatment

Interventions

Experimental target rTMS treatment DEVICE

Participants will undergo MRI-guided identification of the voxel in the left dorsolateral prefrontal cortex (DLPFC) that is most negatively correlated with the functional connectivity of the subgenual anterior cingulate cortex (sgACC) as the stimulation site.

Experimental target rTMS treatment group

Conventional target rTMS treatment DEVICE

participants will receive MRI-guided stimulation at the left DLPFC location.

Conventional target rTMS treatment group

Sham stimulation treatment DEVICE

Participants will receive a sham stimulation treatment designed to simulate the rTMS procedure without generating an effective magnetic field output.

Sham stimulation treatment group

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12 - 18
• Diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed through the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K-SADS-PL), currently in a depressive episode
• Score≥40 on the CDRS-R
• Stable pharmacological treatment: At least 4 weeks of stable psychiatric medication use prior to enrollment, with continuation of the same psychiatric medication regimen throughout the study.

You may not qualify if:

• Psychiatric comorbidities other than anxiety disorders
• Depression with psychotic symptoms
• Young Mania Rating Scale (YMRS) score \>13
• A history of neurological disorders (e.g., epilepsy, brain injury) or severe somatic diseases (e.g., thyroid disorders, lupus, diabetes, pulmonary, hepatic, or renal impairment, major trauma)
• Patients currently using anticonvulsants or high-dose benzodiazepines
• A history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or other neuromodulation treatments
• A history of alcohol or substance abuse or dependence
• Women who are pregnant or breastfeeding
• Current high suicide risk
• Potential complicating factors related to transcranial magnetic stimulation, such as scalp conditions or perforations that may affect magnetic field delivery
• Contraindications to MRI

Sponsors & Collaborators

• First Affiliated Hospital of Chongqing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

RECRUITING

Related Publications (10)

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  PMID: 31901449 BACKGROUND

• Croarkin PE, Elmaadawi AZ, Aaronson ST, Schrodt GR Jr, Holbert RC, Verdoliva S, Heart KL, Demitrack MA, Strawn JR. Left prefrontal transcranial magnetic stimulation for treatment-resistant depression in adolescents: a double-blind, randomized, sham-controlled trial. Neuropsychopharmacology. 2021 Jan;46(2):462-469. doi: 10.1038/s41386-020-00829-y. Epub 2020 Sep 12.

  PMID: 32919400 BACKGROUND

• Allen CH, Kluger BM, Buard I. Safety of Transcranial Magnetic Stimulation in Children: A Systematic Review of the Literature. Pediatr Neurol. 2017 Mar;68:3-17. doi: 10.1016/j.pediatrneurol.2016.12.009. Epub 2017 Jan 4.

  PMID: 28216033 BACKGROUND

• Sigrist C, Vockel J, MacMaster FP, Farzan F, Croarkin PE, Galletly C, Kaess M, Bender S, Koenig J. Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies. Eur Child Adolesc Psychiatry. 2022 Oct;31(10):1501-1525. doi: 10.1007/s00787-022-02021-7. Epub 2022 Jun 24.

  PMID: 35751003 BACKGROUND

• Berlim MT, Van den Eynde F, Daskalakis ZJ. Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depress Anxiety. 2013 Jul;30(7):614-23. doi: 10.1002/da.22060. Epub 2013 Jan 24.

  PMID: 23349112 BACKGROUND

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• Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, Cox GR, Merry SN, Meader N. New generation antidepressants for depression in children and adolescents: a network meta-analysis. Cochrane Database Syst Rev. 2021 May 24;5(5):CD013674. doi: 10.1002/14651858.CD013674.pub2.

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  PMID: 15315995 BACKGROUND

Central Study Contacts

Xinyu Zhou

CONTACT

15823996993; zhouxinyu@cqmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: This study employs a parallel assignment design. Participants will be randomly assigned in a 1:1:1 ratio to the experimental target rTMS treatment group, the conventional target rTMS treatment group, or the sham stimulation group. All three groups will utilize the Blackdolphin TMS Robot device (SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., receiving 20 sessions of rTMS stimulation (10 Hz, 120% RMT) or sham stimulation over 4 weeks (with treatment administered on weekdays), with consistent intervention frequency and procedures. Participants will remain in their assigned group for the entire study duration without any crossover.

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 22, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 26, 2026

Record last verified: 2026-05

Locations

CN (1)