rTMS for Depressed Teens: A Sham-Controlled Trial, Part 2

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

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 investigation also proposes the first study to examine the efficacy of rTMS maintenance therapy in adolescents who have met clinical criteria following acute rTMS treatment. The magnetic resonance (MR) spectroscopy pattern of rTMS response will be analyzed according to previously established protocols.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation (rTMS)

Detailed Description

Part 2 of the study aims to:

• Evaluate the benefit of daily, active, open-label rTMS in Part 1 non-responders.
• Evaluate the benefits of bi-weekly, active, open-label maintenance rTMS treatment for Part 1 responders over the course of 12 months post acute treatment.

• 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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Successful completion of Part 1 of study
• Diagnosis of unipolar major depressive disorder, in a current major depressive episode, without psychotic features
• 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 all study visits at study site.
• Willing to provide informed assent (adolescent) and informed consent (family)

Exclusion Criteria:

• Withdrew from treatment of study Part 1
• Subjects currently on stimulant, antipsychotic, bupropion or tricyclic antidepressant medications.
• Prior 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Part 2 Active; Open-label, active repetitive transcranial magnetic stimulation

Device: Repetitive transcranial magnetic stimulation (rTMS); 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.; Other Names: NeuroStar

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Paul E. Croarkin
• Investigators: Principal Investigator: Paul E Croarkin, DO, Mayo Clinic; Principal Investigator: Mark A George, MD, Medical University of South Carolina

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: March 1, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimate): March 5, 2013

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Adolescent; Depression; Transcranial Magnetic Stimulation; TMS; Teen
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 12-003248 Part 2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes