Major Depressive Disorder
Conditions
Keywords
Teen, Adolescent, Depression, Transcranial Magnetic Stimulation, TMS
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.
Interventions
DEVICERepetitive 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.
Sponsors
Paul E. Croarkin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) | 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) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Active Blinded, active repetitive transcranial magnetic stimulation
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. | 2 |
| Part 1 Sham Blinded, sham repetitive transcranial magnetic stimulation
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. | 4 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Part 1 Active | Total | Part 1 Sham |
|---|---|---|---|
| Age, Continuous | 15 years STANDARD_DEVIATION 1.41 | 16.5 years STANDARD_DEVIATION 1.76 | 17.25 years STANDARD_DEVIATION 1.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 2 / 2 | 0 / 4 |
| serious Total, serious adverse events | 1 / 2 | 1 / 4 |
Outcome results
Primary
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.
Time frame: Within 5 days after Treatment 30 or Last Treatment
Population: Terminated study. Data was not collected nor analyzed
Primary
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.
Time frame: Within 5 days after Treatment 30 or Last Treatment
Population: Terminated study. Data was not collected nor analyzed.
Primary
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.
Time frame: Within 5 days after Treatment 30 or Last Treatment
Population: Terminated study. Data was not collected nor analyzed.