Repetitive Transcranial Magnetic Stimulation for Adolescent Depression: Efficacy, Predictive Biomarkers, and Mechanisms
1 other identifier
interventional
24
1 country
1
Brief Summary
This study will be an open-label 6-week (30 session) trial of active repetitive transcranial magnetic stimulation (rTMS) using a fixed frequency (10 Hz) but varying stimulation intensities using a 3+3 study design for safety and tolerability amongst adolescents. This means that we will only enroll 3 participants at a time and give them rTMS at the stimulation intensity energy of 80% of motor threshold (MT). If all three participants complete the 6 weeks of treatment with no major safety events (i.e. seizure), we will increase the energy for the next 3 participants by 20%. If 1 of the 3 participants has a major safety event, we will enroll 3 more patients at the SAME energy. We will proceed in this manner, increasing by 20% after 3 subjects safely complete treatment at that energy, to a maximum energy of 120% of motor threshold. If 2 participants in each intensity level cohort experience a major safety event, we will discontinue running subjects at that energy level. If this happens at our initial energy level of 80% of MT, we will stop the study. If we reach 2 events in any of the higher energy cohorts, we will return to the previous energy level and complete the remainder of the subjects at that energy level.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Oct 2015
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2015
CompletedFirst Submitted
Initial submission to the registry
October 12, 2015
CompletedFirst Posted
Study publicly available on registry
November 20, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2021
CompletedResults Posted
Study results publicly available
May 18, 2023
CompletedMay 18, 2023
April 1, 2023
6.2 years
October 12, 2015
December 12, 2022
April 24, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in Score on Child Depression Rating Scale - Revised (CDRS-R)
The Children's Depression Rating Scale-Revised (CDRS-R) is a measure of depression severity in adolescents and children of ages 6 to 12. The measure is completed by a clinician based on interviews with the child/adolescent and their parent. The scale includes 17 symptom areas, each rated on a likert scale ranging from 1 to 5 or 7. Depression severity is indiciated by the CDRS-R raw summary score computed by adding the item responses. The summary score ranges from 17 to 113, with a higher score indicating more severe depression and worse outcome. Change in score for each participant was calculated by subtracting their post-rTMS score from their baseline score, such that a positive value indicates a decrease in score from pre to post-treatment.
Baseline to post-treatment
Secondary Outcomes (16)
Change in Score Beck Depression Inventory (BDI-II)
Baseline to post-treatment
Change is Score Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline to post-treatment
Change in Score Temporal Experience of Pleasure Scale (TEPS)
Baseline to post-treatment
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: General Depression
Baseline to post-treatment
Change in Score Young Mania Rating Scale
Baseline to post-treatment
- +11 more secondary outcomes
Study Arms (3)
Period 1: 80% of MT
EXPERIMENTALAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 80% of MT
Period 2: 100% of MT
EXPERIMENTALAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 100% of MT
Period 3: 120% of MT
EXPERIMENTALAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 120% of MT
Interventions
rTMS applies a pulsatile magnetic field to the scalp which painlessly induces electrical currents to the brain. Typically, rTMS is applied to the dorsolateral prefrontal cortex (DLPFC), a brain region that is hypoactive in depression. Whereas standard rTMS stimulates superficial (1cm depth) cortical areas, recent advances in rTMS coil technology support stimulation of deeper (5 cm depth) limbic structures that are also relevant to depression. Other Name: Brainsway rTMS
rTMS applies a pulsatile magnetic field to the scalp which painlessly induces electrical currents to the brain. Typically, rTMS is applied to the dorsolateral prefrontal cortex (DLPFC), a brain region that is hypoactive in depression. Whereas standard rTMS stimulates superficial (1cm depth) cortical areas, recent advances in rTMS coil technology support stimulation of deeper (5 cm depth) limbic structures that are also relevant to depression. Other Name: Brainsway rTMS
rTMS applies a pulsatile magnetic field to the scalp which painlessly induces electrical currents to the brain. Typically, rTMS is applied to the dorsolateral prefrontal cortex (DLPFC), a brain region that is hypoactive in depression. Whereas standard rTMS stimulates superficial (1cm depth) cortical areas, recent advances in rTMS coil technology support stimulation of deeper (5 cm depth) limbic structures that are also relevant to depression. Other Name: Brainsway rTMS
Eligibility Criteria
You may qualify if:
- Diagnosis of Major Depressive Disorder (MDD)
- A CDRS-R score of \>40
- Experiencing a current MDD episode with a duration of ≥ 4 weeks and ≤3 years
- Resistance to treatment, defined by failure to respond adequately to at least one antidepressant treatment, defined by ATR level 1-4 in current episode
- Both child and parent/guardian are English speaking
- Female participants who are sexually active during the course of the study must use a form of birth control for the duration of the study
You may not qualify if:
- Any subject with a clinically defined neurological disorder or insult including, but not limited to, a condition likely to increase the risk of seizure; such as, space occupying brain lesion; any history of seizure; history of cerebrovascular accident; transient ischemic attack within two years; cerebral aneurysm; dementia; brain surgery; history or stroke or family history of epilepsy
- Any subject with an increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure or history of significant head trauma with loss of consciousness for ≥ 5 minutes
- Positive responses to any question on the Transcranial Magnetic Stimulation Adult Safety Screening Questionnaire (TASS)
- Subjects with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute unstable cardiac diseases
- Subjects with conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head within 30 cm of the treatment coil excluding the mouth that cannot safely be removed should be excluded. Examples include cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes
- Subjects with active or inactive implants (including device leads), including deep brain stimulators, cochlear implants, and vagus nerve stimulators
- Inability to locate and quantify a motor threshold as defined in the protocol
- History of treatment with ECT or TMS therapy for any disorders
- Participation in any investigational drug trial within 4 weeks of the baseline visit
- Pregnancy
- IQ \< 80
- Clinically significant laboratory abnormality or medical condition, that in the opinion of the investigator would hinder the subject in completing the procedures required by the study
- Suicide attempt within the previous 6 months that required medical treatment or ≥2 attempts in the past 12 months, or has a clear plan for suicide and states that s/he cannot guarantee that s/he will inform a family member or call his/her psychiatrist or the investigator if the impulse to implement the plan becomes substantial during the study; or, in the investigator's opinion, is likely to attempt suicide within the next 6 months
- Unstable psychotherapy (therapy must be for at least 3 months prior to entry into the study, with no anticipation of change in the frequency or treatment focus of the therapeutic sessions over the duration of the study)
- A diagnosis of substance use disorder, Schizophrenia, Bipolar Disorder, or Autism
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Minnesota
Minneapolis, Minnesota, 55454, United States
Related Publications (1)
Cullen KR, Jasberg S, Nelson B, Klimes-Dougan B, Lim KO, Croarkin PE. Seizure Induced by Deep Transcranial Magnetic Stimulation in an Adolescent with Depression. J Child Adolesc Psychopharmacol. 2016 Sep;26(7):637-41. doi: 10.1089/cap.2016.0070. Epub 2016 Jul 22.
PMID: 27447245DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kathryn Cullen
- Organization
- University of Minnesota
Study Officials
- PRINCIPAL INVESTIGATOR
Kathryn R Cullen, MD
University of Minnesota
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 12, 2015
First Posted
November 20, 2015
Study Start
October 1, 2015
Primary Completion
December 1, 2021
Study Completion
December 1, 2021
Last Updated
May 18, 2023
Results First Posted
May 18, 2023
Record last verified: 2023-04