Treatment Resistant DepressionNCT02611206
Repetitive Transcranial Magnetic Stimulation for Adolescent Depression: Efficacy, Predictive Biomarkers, and Mechanisms
A study testing Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MT, Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MT and Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MT in people with Treatment Resistant Depression, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 18 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MT, Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MT and Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MT
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 1 Dec 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Refusal to cooperate with study procedures
- Recent change in dose of antidepressant medication (within 6 weeks prior to initial evaluation). This includes all antidepressants and any adjunctive psychotropic medications that are being used to address problems related to mood or anxiety (e.g. antipsychotic medications, mood stabilizers.) This does not include stimulant medications that are being used to treat Attention Deficit Hyperactivity Disorder (ADHD).**
- Current treatment with Bupropion at a dose greater than 150mg per day.
- Current treatment with a stimulant medication as an adjunct medication for depression.***
- Current treatment with a stimulant medication for ADHD above FDA recommended dosages.***
- () If the participant has an insufficient number of trials in the current episode, then the participant must also have failed ≥1 and ≤4 trials in a previous episode. Subjects who have been unable to complete an antidepressant trial of adequate dose and duration due to intolerance to antidepressant therapy may be included if they have demonstrated intolerance to ≥4 antidepressant medications within one discrete illness episode (current or previous episode as defined above)
- () If there has been a recent discontinuation of a medication we will require varying lapses of time before study entry depending on medication type as follows: Antidepressant medications = 4 weeks, mood stabilizers (e.g. Lithium, Valproate) = 2 weeks, Antipsychotic medications = 2 weeks, Stimulant medications = 1 week
- () If participants are being treated with stimulant medications as an adjunct strategy for their depression, we will require them to discontinue the stimulant prior to starting the study treatment and wait 1 week before they begin the study as listed above. If the participant is taking a stimulant medication to treat ADHD, they will be allowed to continue the stimulant medication, as long as the dosage is within FDA recommendations.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55454
About this study
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.
Read the detailed description
Adolescents with Treatment Resistant Depression (TRD) (n=30) will be recruited from the inpatient and outpatient adolescent mental health clinical services at UMN and surrounding area.
Adolescents and parents will undergo the consent process and initial clinical evaluation. This initial evaluation will be done using the Kiddie Schedule of Affective Disorders and Schizophrenia (K-SADS-PL 2009) and the Children's Depression Rating Scale-Revised (CDRS-R). Participants and their families will also be asked to complete the Antidepressant Treatment Report (ATR), Beck Depression Inventory (BDI-II), Columbia Suicide Severity Rating Scale (C-SSRS), Inventory of Depression and Anxiety Symptoms (IDAS), Temporal Experience of Pleasure Scale (TEPS), Snaith-Hamilton Pleasure Scale (SHAPS), Young Mania Rating Scale (YMRS), Edinburgh Handedness Scale, the Weschler Abbreviated Scale of Intelligence (WASI) and the Tanner Pubertal Staging Questionnaire. Participants will also be asked to complete the NIH Toolbox, Children's Auditory Verbal Learning Test (CAVLT), and the Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test.
Adolescents with TRD who fit inclusion/exclusion criteria (presence of major depression with CDRS-R raw score > 40; a history of at least one failed treatment trial with an antidepressant [as defined by the Antidepressant Treatment Report]; no history of seizure disorder; no presence of MRI contraindications [e.g. claustrophobia or metallic implants]) will be scheduled for:
- A baseline MRI (described below)
- 6 weeks of the series of rTMS visits described below
- A post-treatment MRI
- A post-treatment clinical assessment (blinded to treatment assignment)
- 6 monthly follow up visits
In the first rTMS visit, the study physician will fit the cap, determine the ideal location for stimulation, and measure MT and MEPa. Adolescents will receive 6 weeks of rTMS, 20 minutes/day, 5 days/week administered by a trained technician. Active treatment will be 43 trains of 10 Hz, stimulation intensity will vary as described above, inter-train interval 20 seconds, 1680 pulses/session. A member of research staff will meet weekly with patients to complete the CDRS-R, monitor treatment tolerance using the Side Effects Form for Children and Adolescents, and measure the MT and MEPa. Adolescents will also complete the BDI-II, C-SSRS-SLV, IDAS, TEPS, YMRS, and SHAPS weekly. At week four, the participants will be asked to repeat the NIH Toolbox, Children's Auditory Verbal Learning Test (CAVLT), and the Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test.
Scanning will take place at the Center for Magnetic Resonance Research on a 3T Siemens Prisma scanner at baseline (after the clinical assessment, before the first treatment) and after the last rTMS treatment. Participants will complete MRI safety forms and provide a urine sample to rule out substance use (all participants) and pregnancy (females only). A high-resolution T1 image will be collected (voxel size=1mm isotropic; TR=2530ms; TE=3.65ms, T1=1100ms, flip angle=7°, 5 minutes). Functional data will be acquired using the Human Connectome Project (HCP)38 multiband echo planar imaging sequence (whole brain T2*-weighted functional volumes, 72 contiguous slices; TR=720ms; TE=34.2ms; flip angle=55o, FOV=212mm; voxel size=2mm isotropic; matrix=106x106; multiband factor=8; 12 minutes) during rest with eyes open while viewing a fixation cross.
Participants will be asked to complete a task fMRI in which they are presented with a series of visual stimuli, (human faces of varying emotion expressions with positive, negative or neutral words printed over the faces). During the task, participants will be asked to decide whether the words printed over the faces are positive or negative regardless of the emotion of the face shown. Each subject will complete four distinct blocks of the task.
After the completion of rTMS sessions, all participants will undergo a final assessment during which they will be asked to meet with evaluators again to complete the CDRS-R. They will also be asked to complete the BDI-II, C-SSRS, TEPS, SHAPS, IDAS and NIH Toolbox.
After the completion of all rTMS sessions, participants will be asked to return to see researchers every month for 6 months to assess length of treatment response.
- Conditions
- Treatment Resistant Depression
- Being tested
- Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MT, Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MT, Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MT
- Keywords
- rTMS
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MTDevice
Also called 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
Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MTDevice
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
Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MTDevice
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
| Study group | Role | What they receive |
|---|---|---|
| Period 1: 80% of MT | Experimental | All participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 80% of MT Receives: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MT |
| Period 2: 100% of MT | Experimental | All participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 100% of MT Receives: Device: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MT |
| Period 3: 120% of MT | Experimental | All participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 120% of MT Receives: Device: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to post-treatment
Secondary outcomes (16)
Change in Score Beck Depression Inventory (BDI-II)
The Beck Depression Inventory (BDI-II) is a 21-item self-report measure of depression severity in adolescents and adults. Each item is measured on a likert scale ranging from 0 to 3. A total score is calculated by adding item responses and can range from 0 to 63, 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.
Measured: Baseline to post-treatment
Change is Score Columbia Suicide Severity Rating Scale (C-SSRS)
Columbia Suicide Severity Rating Scale (C-SSRS- recent version) is a 10-item measure of suicidal ideation and behavior. Participants were assigned a score between 0 and 8, with higher scores indicating the endorsement of more severe suicidal ideation or behavior (a worse outcome) and a score of "0" indicating no suicidal ideation or behavior (better 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.
Measured: Baseline to post-treatment
Change in Score Temporal Experience of Pleasure Scale (TEPS)
The Temporal Experience of Pleasure Scale (TEPS) is an 18-item self-report measure of the tendency to anticipate and experience pleasure. Each item is rated on a likert scale ranging from 1 (very false for me) to 6 (very true for me). A total score is calculated by adding item responses and ranges from 18 to 108, such that higher scores indicate greater anticipation and experience of pleasure and better 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.
Measured: Baseline to post-treatment
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: General Depression
64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Subscale scores are calculated by adding responses for items corresponding to the subscale, with higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-treatment
Change in Score Young Mania Rating Scale
The Young Mania Rating Scale is a 11-item measure of manic symptoms. Some items are rated on a likert scale ranging from 0 to 4 and some items are rated on a scale ranging from 0 to 8. Total scores range from 0 to 60, with a higher score indiciating higher levels of mania 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.
Measured: Baseline to post-treatment
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Dysphoria
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Lassitude
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Insomnia
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Suicidality
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Appetite Loss
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Appetite Gain
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Ill Temper
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Well Being
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Social Anxiety
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Panic
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Traumatic Intrusions
The Inventory of Depression and Anxiety Symptoms (IDAS) is a 64-item measure of mood and anxiety disorder symptoms. Each item is rated on a likert scale ranging from 1 (not at all) to 5 (extremely). The measure includes 2 broad subscales of general depresson (20 items; score range: 20-100) and dysphoria (10 items; score range: 10-50) as well as 10 specific symptom scales: Lassitude (6 items; score range: 6-30), Insomnia (6 items; score range: 6-30), Suicidality (6 items; score range: 6-30), Well-Being (8 items; score range: 8-40), Social Anxiety (5 items; score range: 5-25), Appetite Loss (3 items; score range: 3-15), Appetite Gain (3 items; score range: 3-15), Ill Temper (5 items; score range: 5-25), Panic (8 items; score range: 8-40), and Traumatic Intrusions (4 items; score range: 4-20). Higher scores on each subscale except the well-being subscale indicating poorer outcomes. Higher scores on well-being subscale indicates better outcome.
Measured: Baseline to post-rTMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startOct 2015
- Primary completion1 Dec 2021
- Study completion1 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathryn R Cullen, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02611206
- Sponsor's protocol ID
- PSYCH-2016-18311
- Status last verified
- Apr 2023
- First submitted
- 12 Oct 2015
- Last updated
- 18 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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.
PubMed 27447245
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repetitive Transcranial Magnetic Stimulation for Adolescent Depression: Efficacy, Predictive Biomarkers, and Mechanisms
- ClinicalTrials.gov ID
- NCT02611206
- Acronym / sponsor ID
- PSYCH-2016-18311
- Conditions
- Treatment Resistant Depression
- Keywords
- rTMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 1 Dec 2021 (actual)
- First posted
- 20 Nov 2015 (estimated)
- Results
- Posted 18 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Adolescents with Treatment Resistant Depression (TRD) (n=30) will be recruited from the inpatient and outpatient adolescent mental health clinical services at UMN and surrounding area.
Adolescents and parents will undergo the consent process and initial clinical evaluation. This initial evaluation will be done using the Kiddie Schedule of Affective Disorders and Schizophrenia (K-SADS-PL 2009) and the Children's Depression Rating Scale-Revised (CDRS-R). Participants and their families will also be asked to complete the Antidepressant Treatment Report (ATR), Beck Depression Inventory (BDI-II), Columbia Suicide Severity Rating Scale (C-SSRS), Inventory of Depression and Anxiety Symptoms (IDAS), Temporal Experience of Pleasure Scale (TEPS), Snaith-Hamilton Pleasure Scale (SHAPS), Young Mania Rating Scale (YMRS), Edinburgh Handedness Scale, the Weschler Abbreviated Scale of Intelligence (WASI) and the Tanner Pubertal Staging Questionnaire. Participants will also be asked to complete the NIH Toolbox, Children's Auditory Verbal Learning Test (CAVLT), and the Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test.
Adolescents with TRD who fit inclusion/exclusion criteria (presence of major depression with CDRS-R raw score > 40; a history of at least one failed treatment trial with an antidepressant [as defined by the Antidepressant Treatment Report]; no history of seizure disorder; no presence of MRI contraindications [e.g. claustrophobia or metallic implants]) will be scheduled for:
- A baseline MRI (described below)
- 6 weeks of the series of rTMS visits described below
- A post-treatment MRI
- A post-treatment clinical assessment (blinded to treatment assignment)
- 6 monthly follow up visits
In the first rTMS visit, the study physician will fit the cap, determine the ideal location for stimulation, and measure MT and MEPa. Adolescents will receive 6 weeks of rTMS, 20 minutes/day, 5 days/week administered by a trained technician. Active treatment will be 43 trains of 10 Hz, stimulation intensity will vary as described above, inter-train interval 20 seconds, 1680 pulses/session. A member of research staff will meet weekly with patients to complete the CDRS-R, monitor treatment tolerance using the Side Effects Form for Children and Adolescents, and measure the MT and MEPa. Adolescents will also complete the BDI-II, C-SSRS-SLV, IDAS, TEPS, YMRS, and SHAPS weekly. At week four, the participants will be asked to repeat the NIH Toolbox, Children's Auditory Verbal Learning Test (CAVLT), and the Delis-Kaplan Executive Function System (D-KEFS) Trail Making Test.
Scanning will take place at the Center for Magnetic Resonance Research on a 3T Siemens Prisma scanner at baseline (after the clinical assessment, before the first treatment) and after the last rTMS treatment. Participants will complete MRI safety forms and provide a urine sample to rule out substance use (all participants) and pregnancy (females only). A high-resolution T1 image will be collected (voxel size=1mm isotropic; TR=2530ms; TE=3.65ms, T1=1100ms, flip angle=7°, 5 minutes). Functional data will be acquired using the Human Connectome Project (HCP)38 multiband echo planar imaging sequence (whole brain T2*-weighted functional volumes, 72 contiguous slices; TR=720ms; TE=34.2ms; flip angle=55o, FOV=212mm; voxel size=2mm isotropic; matrix=106x106; multiband factor=8; 12 minutes) during rest with eyes open while viewing a fixation cross.
Participants will be asked to complete a task fMRI in which they are presented with a series of visual stimuli, (human faces of varying emotion expressions with positive, negative or neutral words printed over the faces). During the task, participants will be asked to decide whether the words printed over the faces are positive or negative regardless of the emotion of the face shown. Each subject will complete four distinct blocks of the task.
After the completion of rTMS sessions, all participants will undergo a final assessment during which they will be asked to meet with evaluators again to complete the CDRS-R. They will also be asked to complete the BDI-II, C-SSRS, TEPS, SHAPS, IDAS and NIH Toolbox.
After the completion of all rTMS sessions, participants will be asked to return to see researchers every month for 6 months to assess length of treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Period 1: 80% of MT | Experimental | Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MTAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 80% of MT |
| Period 2: 100% of MT | Experimental | Device: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MTAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 100% of MT |
| Period 3: 120% of MT | Experimental | Device: Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MTAll participants who qualify will undergo 6 weeks of open-label rTMS with a stimulation intensity of 120% of MT |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MTAlso: Brainsway rTMSrTMS 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 | Device | Period 1: 80% of MT |
| Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MTrTMS 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 | Device | Period 2: 100% of MT |
| Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MTrTMS 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 | Device | Period 3: 120% of MT |
Primary outcome
Change in Score on Child Depression Rating Scale - Revised (CDRS-R)
Time frame: Baseline to post-treatment
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.
16 secondary outcomes
Change in Score Beck Depression Inventory (BDI-II)
Time frame: Baseline to post-treatment
Change is Score Columbia Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline to post-treatment
Change in Score Temporal Experience of Pleasure Scale (TEPS)
Time frame: Baseline to post-treatment
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: General Depression
Time frame: Baseline to post-treatment
Change in Score Young Mania Rating Scale
Time frame: Baseline to post-treatment
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Dysphoria
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Lassitude
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Insomnia
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Suicidality
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Appetite Loss
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Appetite Gain
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Ill Temper
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Well Being
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Social Anxiety
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Panic
Time frame: Baseline to post-rTMS
Change in Score Inventory of Depression and Anxiety Symptoms (IDAS) Subscale: Traumatic Intrusions
Time frame: Baseline to post-rTMS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27447245Cullen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathryn R Cullen, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Repetitive Transcranial Magnetic Stimulation (rTMS): intensity 80% MT, Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 100% of MT and Device: Active Repetitive Transcranial Magnetic Stimulation (rTMS); Stimulation intesity: 120% of MT in people with Treatment Resistant Depression, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Score on Child Depression Rating Scale - Revised (CDRS-R) (time frame: Baseline to post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02611206, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2023; AzTrials last refreshed its copy on 1 Nov 2026.