Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression

NCT03363919 | Completed Results DMC FDA Device

• 2 other identifiers: 17-0049581R01MH113700-01
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The Researchers are going to gather information regarding the use of rTMS as a treatment for depression in adolescents with Major Depressive Disorder. The researchers also hope to learn if measures of brain activity (cortical excitability and inhibition) collected with transcranial magnetic stimulation (TMS) can be used to identify which patients will benefit from certain types of rTMS treatment.

Conditions

Major Depressive Disorder

Keywords

adolescent; biomarkers

Outcome Measures

Primary Outcomes (1)

• Total Children's Depression Rating Scale, Revised (CDRS-R) Score

  CDRS-R is a 17-item scale, with items ranging from 1 to 5 or 1 to 7 (possible total score from 17 to 113), rated by a clinician via interviews with the child and parent. A score of ≥40 is indicative of depression, whereas a score ≤28 is often used to define remission (minimal or no symptoms)

  6 weeks

Secondary Outcomes (1)

• Change in Intracortical Facilitation (ICF)

  baseline, 6 weeks

Study Arms (2)

1 Hz left prefrontal rTMS

ACTIVE COMPARATOR

36 sessions of 1 Hz rTMS at 120% motor threshold applied to the left prefrontal cortex. Each session is 2400 continuous pulses.

Device: NeuroStar TMS Therapy® System; Device: NeuroStar XPLOR®

10 Hz left prefrontal rTMS

ACTIVE COMPARATOR

36 sessions of 10 Hz rTMS at 120% motor threshold applied to the left prefrontal cortex. Each session is 2400 pulses with 4 seconds on and 36 seconds off.

Device: NeuroStar TMS Therapy® System; Device: NeuroStar XPLOR®

Interventions

NeuroStar TMS Therapy® System DEVICE

The NeuroStar TMS Therapy® System is a computerized electromechanical instrument that produces and delivers brief duration, rapidly alternating (pulsed) magnetic fields to induce electrical currents in localized regions of the cerebral cortex. It is a non-invasive tool used for the treatment of Participants with Major Depressive Disorder (MDD) who have not achieved sufficient clinical benefit from antidepressant pharmacotherapy.

1 Hz left prefrontal rTMS; 10 Hz left prefrontal rTMS

NeuroStar XPLOR® DEVICE

NeuroStar XPLOR® is a clinical research option for the NeuroStar TMS Therapy System that provides features necessary to conduct randomized controlled trials and other TMS research.

1 Hz left prefrontal rTMS; 10 Hz left prefrontal rTMS

Eligibility Criteria

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

You may qualify if:

• Depressed adolescent participants will have a primary diagnoses of MDD based on a clinical and structured interview with the MINI
• Depression symptoms severity of a 40 or greater based on evaluation with the Children's Depression Rating Scale Revised (CDRS-R) at screening and baseline visits. Further, the total score of the baseline CDRS-R score must not have had a 25% or greater decrease from the screening CDRS-R score
• The duration of the current episode of depression must be 4 weeks or more but 3 years or less.
• For any participant currently receiving antidepressant medication, the referring clinician must determine that insufficient benefit is being received from this treatment and it is clinically appropriate to discontinue the existing antidepressant.
• Participants in psychotherapy are eligible provided that this was initiated 4 weeks prior to enrollment and that the frequency of visits will be maintained during study participation.

You may not qualify if:

• A positive urine drug screen at baseline
• Seizure history
• Family history of epilepsy in a first degree relative
• Head trauma with loss of consciousness for greater than 5 minutes
• Any true positive findings on the rTMS safety screening form.
• Any concurrent psychotropic medications (for potential participants receiving antidepressants or psychotropic medications, the referring clinician must determine that insufficient benefit is being received from the treatment and if clinically appropriate, discontinue existing antidepressants and other psychotropic medications)
• Prohibited concomitant medications (See Appendix A)
• Pregnancy or suspected pregnancy in female Participants (assessed with urine pregnancy test)
• Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the subject's head within 30 cm of the treatment coil excluding the mouth that cannot safely be removed. Examples include cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes.
• Prior brain surgery
• Risk for increased intracranial pressure such as a brain tumor
• Any unstable medical condition
• History of treatment with ECT or TMS Therapy for any disorder
• Use of any investigational drug within 4 weeks of the baseline visit
• Initiation of a new psychotherapeutic treatment within the past 4 weeks

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Mental Health (NIMH): collaborator
• Neuronetics: collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (9)

• Wall CA, Croarkin PE, Maroney-Smith MJ, Haugen LM, Baruth JM, Frye MA, Sampson SM, Port JD. Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder. J Child Adolesc Psychopharmacol. 2016 Sep;26(7):582-9. doi: 10.1089/cap.2015.0217. Epub 2016 Feb 5.

  PMID: 26849202 BACKGROUND

• Croarkin PE, Nakonezny PA, Wall CA, Murphy LL, Sampson SM, Frye MA, Port JD. Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents. Psychiatry Res Neuroimaging. 2016 Jan 30;247:25-33. doi: 10.1016/j.pscychresns.2015.11.005. Epub 2015 Nov 27.

  PMID: 26651598 BACKGROUND

• Croarkin PE, Wall CA, Lee J. Applications of transcranial magnetic stimulation (TMS) in child and adolescent psychiatry. Int Rev Psychiatry. 2011 Oct;23(5):445-53. doi: 10.3109/09540261.2011.623688.

  PMID: 22200134 BACKGROUND

• Wall CA, Croarkin PE, Sim LA, Husain MM, Janicak PG, Kozel FA, Emslie GJ, Dowd SM, Sampson SM. Adjunctive use of repetitive transcranial magnetic stimulation in depressed adolescents: a prospective, open pilot study. J Clin Psychiatry. 2011 Sep;72(9):1263-9. doi: 10.4088/JCP.11m07003.

  PMID: 21951987 BACKGROUND

• Croarkin PE, Nakonezny PA, Husain MM, Melton T, Buyukdura JS, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder. JAMA Psychiatry. 2013 Mar;70(3):291-9. doi: 10.1001/2013.jamapsychiatry.24.

  PMID: 23303429 BACKGROUND

• Donaldson AE, Gordon MS, Melvin GA, Barton DA, Fitzgerald PB. Addressing the needs of adolescents with treatment resistant depressive disorders: a systematic review of rTMS. Brain Stimul. 2014 Jan-Feb;7(1):7-12. doi: 10.1016/j.brs.2013.09.012.

  PMID: 24527502 BACKGROUND

• Krishnan C, Santos L, Peterson MD, Ehinger M. Safety of noninvasive brain stimulation in children and adolescents. Brain Stimul. 2015 Jan-Feb;8(1):76-87. doi: 10.1016/j.brs.2014.10.012. Epub 2014 Oct 28.

  PMID: 25499471 BACKGROUND

• Delaney K, Nakonezny PA, Buyuktaskin D, Carrasco LS, Athreya AP, Romanowicz M, Shekunov J, Vande Voort JL, Croarkin PE. Trajectories of Irritability Improvement in Depressed Adolescents Treated With 1 Hz and 10 Hz Transcranial Magnetic Stimulation. J Clin Psychiatry. 2025 Apr 9;86(2):24m15684. doi: 10.4088/JCP.24m15684.

  PMID: 40215375 DERIVED

• Lewis CP, Nakonezny PA, Sonmez AI, Ozger C, Garzon JF, Camsari DD, Yuruk D, Romanowicz M, Shekunov J, Zaccariello MJ, Vande Voort JL, Croarkin PE. A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression. J Am Acad Child Adolesc Psychiatry. 2025 Oct;64(10):1179-1191. doi: 10.1016/j.jaac.2024.08.487. Epub 2024 Sep 6.

  PMID: 39245178 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Paul E. Croarkin, D.O., M.S.
• Organization: Mayo Clinic

Croarkin.Paul@mayo.edu

507-293-2557

Study Officials

• Paul E Croarkin, DO

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: In both phases of the study (phase I and phase II) participants and study team members completing clinical rating scales will be blinded to treatment assignment. The study team member completing clinical rating scales and analyzing TMS neurophysiology measures will not be allowed in the treatment suite during therapeutic rTMS sessions (10 Hz, 1 Hz, iTMS, or cTBS).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 6, 2017
• Study Start: September 24, 2018
• Primary Completion: March 3, 2023
• Study Completion: March 3, 2023
• Last Updated: February 1, 2024
• Results First Posted: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)