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

Major Depressive Disorder Clinical Trial

Official title:

Glutamatergic and GABAergic Biomarkers in rTMS for Adolescent Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03363919
• Other study ID #: 17-004958
• Secondary ID: 1R01MH113700-01
• Status: Completed
• Phase: N/A
• Start date: September 24, 2018
• Est. completion date: March 3, 2023

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: March 3, 2023
• Est. primary completion date: March 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Mental Health (NIMH), Neuronetics

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Intracortical Facilitation (ICF)	ICF measures were collected with surface electromyography. A subthreshold conditioning stimulus (CS) was set to 80% of resting motor threshold (RMT) preceding a suprathreshold test stimulus (TS), which was calibrated to produce an average motor evoked potential (MEP) of 0.5 to 1.5 millivolt peak-to-peak amplitude in the contralateral abductor pollicis brevis (APB) muscle. Conditioning stimuli were delivered to the motor cortex prior to the TS in 15 msec interstimulus intervals. Changes in TS MEP was expressed as a percentage of the mean unconditioned MEP amplitude.	baseline, 6 weeks

External Links

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