rTMS for Depressed Teens: A Sham-Controlled Trial, Part 1

Study Overview
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Brief Summary
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This research proposal aims to better understand the neurobiology of depression in adolescents and how repetitive transcranial magnetic stimulation (rTMS) may therapeutically impact brain function and mood. This study will be the first to use a randomized, double-blinded, sham-controlled approach to the investigation of rTMS therapy for depressed adolescents. This approach will allow for the validation of rTMS treatment outcomes in the depressed adolescent population in a scientifically rigorous manner. The magnetic resonance (MR) spectroscopy pattern of rTMS response will be analyzed according to previously established protocols.

Detailed Description
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Part 1 of the study aims to: Evaluate the antidepressant effects of daily, active rTMS (when compared with sham treatment) in adolescents meeting criteria for Major Depressive Disorder, single or recurrent episode. Evaluate, by proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla(3T), neurometabolic biomarkers at the beginning and end of each study phase. Define regional specificity [anterior cingulate (AC) and left dorsolateral prefrontal cortex (L-DLPFC)] of cerebral metabolites(i.e. glutamate and glutamine) in adolescent depression. Study whether specific neurochemical resonances are associated with response, remission, and/or maintenance of improvement of clinical depressive symptoms when rTMS is used to treat adolescent depression.

Official Title
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A Randomized, Double-Blinded, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Repetitive transcranial magnetic stimulation (rTMS)


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 12 and less than 22 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 Savella (milnacipran HCl) - 25mg to 200mg Zoloft (sertraline HCl) - 25mg to 200mg Subjects able to attend at least 31 study visits at study site. 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: 12 Years
Maximum Age: 21 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part 1 Active<br>Blinded, active repetitive transcranial magnetic stimulation | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Active treatments with repetitive transcranial magnetic stimulation (rTMS) consists of treatment settings of 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.<br>* Other names: NeuroStar XPLOR;|
| Sham Comparator: Part 1 Sham<br>Blinded, sham repetitive transcranial magnetic stimulation | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* Active treatments with repetitive transcranial magnetic stimulation (rTMS) consists of treatment settings of 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.<br>* Other names: NeuroStar XPLOR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Post Treatment 30 or Last Treatment (in the Case 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. | Within 5 days after Treatment 30 or Last Treatment | 
| Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal) | The Clinical Global Impression - Severity (CGI-S) is a standardized assessment utilizing a 7-point scale with which the clinician rates the severity of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis. | Within 5 days after Treatment 30 or Last Treatment | 
| Mean Clinical Global Impression - Improvement (CGI-I) Score Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal) | The Clinical Global Impression - Improvement (CGI-I) is a standardized assessment utilizing a 7-point scale with which the clinician rates the degree to which the severity of the subject's depressive illness has improved or worsened compared to baseline severity. | Within 5 days after Treatment 30 or Last Treatment | 

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