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

NCT ID: NCT03363919

Last Updated: 2024-02-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-24

Study Completion Date

2023-03-03

Brief Summary

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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.

Detailed Description

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Phase I is a double-blind, randomized, biomarker-stratified trial of 1 Hz vs. 10 Hz rTMS. Phase II is for participants who do not respond to Phase I treatment and is a biomarker guided, double-blind trial of continuous vs intermittent theta burst stimulation (TBS). Please note that transcranial magnetic stimulation (TMS) biomarkers will be collected in this protocol during the course of the proposed interventions. Participants in Phase I will be offered enrollment in a separate protocol with baseline and posttreatment 7 Tesla Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) scans

Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers
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).

Study Groups

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1 Hz left prefrontal rTMS

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

Group Type ACTIVE_COMPARATOR

NeuroStar TMS Therapy® System

Intervention Type 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.

NeuroStar XPLOR®

Intervention Type 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.

10 Hz left prefrontal rTMS

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.

Group Type ACTIVE_COMPARATOR

NeuroStar TMS Therapy® System

Intervention Type 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.

NeuroStar XPLOR®

Intervention Type 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.

Interventions

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NeuroStar TMS Therapy® System

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.

Intervention Type DEVICE

NeuroStar XPLOR®

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* The following psychiatric comorbidities are exclusionary: psychotic disorders, bipolar disorders, anorexia nervosa, bulimia nervosa, and substance use disorders within the past year (with the exception of caffeine and tobacco)
* 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
* Suicide attempt within the previous 6 months that required medical treatment or ≥ 2 attempts in the past 12 months, or has a clear cut plan for suicide and states that he/she cannot guarantee that he/she will inform a family member or call his/her psychiatrist or the investigator if the impulse to implement the plan becomes substantial during the study; or, in the investigator's opinion, is likely to attempt suicide within the next 6 months.
Minimum Eligible Age

12 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Neuronetics

OTHER

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Paul E. Croarkin

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Paul E Croarkin, DO

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26849202 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26651598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22200134 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21951987 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23303429 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24527502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25499471 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40215375 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39245178 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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1R01MH113700-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-004958

Identifier Type: -

Identifier Source: org_study_id

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