Study of Repetitive Transcranial Magnetic Stimulation (rTMS) in Depressed Teens

Study Overview
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Brief Summary
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This research study aims to test the safety and effectiveness of repetitive transcranial magnetic stimulation (rTMS) on teens with depression. The study also seeks to understand how rTMS treatment affects the neurobiology of teens with depression.

Detailed Description
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This study aims to: Evaluate the antidepressant effect and safety of rTMS in adolescents meeting criteria for major depressive disorder, single or recurrent episode. Evaluate, by proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla (3T), the regional specificity [anterior cingulate (AC) vs. left dorsolateral prefrontal cortex (L-DLPFC)] of cerebral metabolites (glutamate and glutamine) in adolescent depression and study whether glutamine resonances are associated with response or remission of clinical depressive symptoms when rTMS is used to treat adolescent depression. Evaluate the accuracy of an efficient method for locating the F3 position (i.e., L-DLPFC) through comparison with magnetic resonance imaging (MRI).

Official Title
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An Open-Label Eight-Week Trial of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents: Mechanisms of Response

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of unipolar major depressive disorder, in a current major depressive episode, without psychotic features Pretreatment CDRS-R Raw score ≥ 40 Age is at least 13 and less than 19 years Ongoing, stable dose antidepressant therapy for at least 6 weeks to include the following antidepressants (with dosing range): Celexa (citalopram hydrobromide) - 10 to 60mg Cymbalta (duloxetine) - 40mg to 120mg Desyrel (trazodone HCl) - 12.5mg to 150mg Effexor (venlafaxine HCl) - 37.5mg to 300mg Luvox (fluvoxamine maleate) - 25mg to 200mg Lexapro (escitalopram oxalate) - 10mg to 40mg Paxil (paroxetine HCl) - 10mg to 50mg Pristiq (desvenlafaxine) - 50mg to 100mg Prozac (fluoxetine HCl) - 10mg to 80mg Remeron (mirtazapine) - 7.5mg to 45mg Zoloft (sertraline HCl) - 25mg to 200mg Subjects able to attend at least 31 study visits at Mayo Clinic - Rochester Willing to provide informed assent (adolescent) and informed consent (family) Exclusion Criteria: Subjects currently on stimulant, antipsychotic, bupropion or tricyclic antidepressant medications. Prior rTMS, vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT) Contraindication to MRI Contraindication to rTMS (history of neurological disorder such as seizures, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for >15 minutes, history of stroke, family history of epilepsy, intracardiac lines, Anticoagulant, immune suppressive and/or chemotherapy, or those who received any of these therapies within 3 months before enrollment in the study Unstable medication conditions such as hematological or infectious (e.g., human immunodeficiency virus-HIV) disorders, implanted electronic device, metal in the head, or pregnancy) History of schizophrenia, schizoaffective disorder, other [non mood disorder] psychosis, depression secondary to a medical condition, mental retardation, substance dependence or abuse within the past year (except nicotine), bipolar disorder, psychotic features in this or previous episodes, amnestic disorder, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder History of autoimmune, endocrine, viral, or vascular disorder. Unstable cardiac disease, uncontrolled hypertension, or sleep apnea Active suicidal intent or plan, or history of attempt within the past 6 months

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial Magnetic Stimulation<br>Open-label course of 30 daily treatments with repetitive transcranial magnetic stimulation (rTMS) at 120% magnetic field intensity relative to the patient's resting motor threshold, at 10 pulses per second (10 Hz) for 4 seconds, with an intertrain interval of 26 seconds for a total of 75 trains per treatment session. | Device: Transcranial Magnetic Stimulation<br>* 30 daily treatments of (over 6-8 weeks) of 10 Hz rTMS at 120% motor threshold, applied to the left dorsolateral prefrontal cortex with 3,000 stimulations per treatment<br>* Other names: NeuroStar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Children's Depression Rating Scale-Revised (CDRS-R) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | The Children's Depression Rating Scale-Revised (CDRS-R) is a validated, 17-item, semi-structured clinician rating tool to assess severity of depression with subject and parental input for 14 of the 17 items. | 5 days of Treatment 30 or Last Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | The Clinical Global Impression - Severity (CGI-S) is a standardized assessment utilizing a 7-point scale with which the clinician rates severity of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= normal, not ill at all; 7= among the most ill patients; larger number indicates greater severity of symptoms or worse outcome). | Within 5 days of Treatment 30 or Last Treatment | 
| The Clinical Global Impression - Improvement (CGI-I) | The Clinical Global Impression - Improvement (CGI-I) is a standardized assessment utilizing a 7-point scale with which the clinician rates improvment of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= very much improved, 7=very much worse) larger number indicates greater severity of symptoms or worse outcome). | Within 5 days of 30 treatments or after last treatment in case of early withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescent Depression, Transcranial Magnetic Stimulation