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

• ClinicalTrials.gov Identifier: NCT01804270
• Recruitment Status: Terminated
• First Posted: March 5, 2013
• Results First Posted: January 19, 2022
• Last Update Posted: January 19, 2022
• Sponsor: Paul E. Croarkin
• Information provided by (Responsible Party): Paul E. Croarkin, Mayo Clinic

Tracking Information

• First Submitted Date: March 1, 2013
• First Posted Date: March 5, 2013
• Results First Submitted Date: December 20, 2021
• Results First Posted Date: January 19, 2022
• Last Update Posted Date: January 19, 2022
• Actual Study Start Date: April 2013
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2021)

• 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) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.
• Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.
• Mean Clinical Global Impression - Improvement (CGI-I) Score Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.

Original Primary Outcome Measures (submitted: March 1, 2013)

• 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) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.
• Mean change from Baseline in Clinical Global Impression - Severity (CGI-S) post Treatment 30 or Last Treatment (in the case of early withdrawal) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.
• Mean Clinical Global Impression - Improvement (CGI-I) Score post Treatment 30 or Last Treatment (in the case of early withdrawal) [ Time Frame: Within 5 days after Treatment 30 or Last Treatment ]
  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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: rTMS for Depressed Teens: A Sham-Controlled Trial, Part 1
• Official Title: A Randomized, Double-Blinded, Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

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 Name: NeuroStar XPLOR

Study Arms

• Active Comparator: Part 1 Active
  Blinded, active repetitive transcranial magnetic stimulation
  Intervention: Device: Repetitive transcranial magnetic stimulation (rTMS)
• Sham Comparator: Part 1 Sham
  Blinded, sham repetitive transcranial magnetic stimulation
  Intervention: Device: Repetitive transcranial magnetic stimulation (rTMS)

• Publications *: Sonmez AI, Kucuker MU, Lewis CP, Kolla BP, Doruk Camsari D, Vande Voort JL, Schak KM, Kung S, Croarkin PE. Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 8;97:109763. doi: 10.1016/j.pnpbp.2019.109763. Epub 2019 Oct 18.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 20, 2021): 6
• Original Estimated Enrollment (submitted: March 1, 2013): 50
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01804270
• Other Study ID Numbers: 12-003248 Part 1
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Paul E. Croarkin, Mayo Clinic
• Original Responsible Party: Christopher Wall, Mayo Clinic, Assistant Professor of Child and Adolescent Psychiatry
• Current Study Sponsor: Paul E. Croarkin
• Original Study Sponsor: Christopher Wall
• Collaborators: Not Provided

Investigators

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

• PRS Account: Mayo Clinic
• Verification Date: December 2021