Clinical trial NCT01804270: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: Teen
Adolescent
Depression
Transcranial Magnetic Stimulation
TMS
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2013-03-05
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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)
timeFrame: Within 5 days after Treatment 30 or Last Treatment
measure: Mean Change From Baseline in Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal)
timeFrame: Within 5 days after Treatment 30 or Last Treatment
measure: Mean Clinical Global Impression - Improvement (CGI-I) Score Post Treatment 30 or Last Treatment (in the Case of Early Withdrawal)
timeFrame: Within 5 days after Treatment 30 or Last Treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Mayo Clinic
name: Paul E Croarkin, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Mark A George, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.