Depression
Conditions
Keywords
Adolescent Depression, Teen Depression
Brief summary
This is an open label, pilot, feasibility study evaluating effects of Intermittent Theta Burst Transcranial Magnetic Stimulation (iTBS) on 5 eligible adolescents for the treatment of depression. Safety and tolerability will be evaluated with changes in depression scores, and suicidality and non-suicidal self injurious behavior will also be monitored for exploratory and safety measures.
Detailed description
This study will investigate the efficacy and durability of the effects of Intermittent Theta Burst Stimulation (iTBS) in adolescent depression by measuring changes in clinical ratings before, during, and after 4 weeks of treatment, up to 12 weeks following treatment. The investigators expect that subjects will show: improvement in symptoms over 20 iTBS sessions as measured by the Children's Depression Rating Scale Revised (CDRS-R), Hamilton Depression Rating Scale (HAM-D) and Non-suicidal Self Injurious Behavior (NSSIB) measures, and persistence of this reduction of depressive symptoms through the 12 weeks follow up period of the study. In this study, the investigators will investigate the safety of the effects of iTBS in adolescent depression. The investigators will investigate safety of the treatment regimen by assessing suicidality. The investigators expect suicidal thoughts and behavior will reduce with iTBS treatment as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) and a psychiatrist's clinical assessment. The investigators also expect that those with NSSIB at the start of the trial will have less after iTBS treatments. The investigators do not expect any change in cognition measured with the Mini Mental Status Exam (MMSE), Trails B, and List Generation. The investigators will investigate treatment feasibility by assessing treatment completion and withdrawal. The investigators define the feasibility of iTBS will be defined as feasible by as completion of 15/20 (75%) iTBS treatment sessions by all subjects and withdrawal from treatment of no more than one of five subjects (20%) due to intolerable side effects or persistent symptoms of MDD. Investigation of efficacy, durability, safety as well as feasibility simultaneously is essential in this preliminary study of the use of iTBS in adolescents in order to justify a larger future study. This study will include a screening visit, 20 iTBS treatments, and 3 planned follow up visits.
Interventions
DEVICEiTBS Device/Motor Threshold Coil
Motor Threshold determination, done prior to starting treatments, determines the location and the intensity for the iTBS treatments. A magnetic field is applied with increasing intensity stimulating the motor region of the brain until there is thumb movement; this indicates the intensity of the treatments; the location for treatment is in the sensory area parallel to this location.
DEVICEiTBS Device/Treatment Coil
iTBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz very quickly). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatments lasts approximately 3 minutes, and sessions are provided 20 times (Monday-Friday for 4 consecutive weeks).
Sponsors
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* A score of greater than 40 on the CDRS-R and 17 on HAM-D. * Documentation of DSM-V criteria for current MDD or TRD will be required for study entry. * Patients may be on antidepressant medication at a stable dose or receiving psychotherapy with a licensed provider during the active phase of TMS treatment for 4 weeks. * Ability to provide consent and take part in questionnaires and scales (i.e.: not currently intellectually disabled). * The presence of suicidality or NSSIB are not required to enter this study. Although our secondary end-points include suicidality, and the investigators are also exploring NSSIB, and thus this may not lead to many data, the investigators' plan is to use data from this study to justify a larger study where this can be more robustly investigated.
Exclusion criteria
* Past or current diagnosis of bipolar disorder, psychosis, seizures or traumatic brain injury. * Presence of intracranial metallic implants or fragments, which is a contraindication for TMS. * Lifetime history of (or currently present) epilepsy. * Current diagnosis of substance abuse, eating disorder, PTSD (Post Traumatic Stress Disorder), or intellectual disability.\* Nicotine use disorder will not directly preclude a potential subject from this study. Although chronic nicotine use does effect central nervous system excitability, what would be more confounding to our study would be if there is a sudden change in nicotine use during the treatment phase, as this may affect the motor threshold. Inclusion will however be at the PI's discretion. * Current imminent suicide ideation or other clinical reasons for inpatient psychiatric hospitalization. * Currently pregnant. There is currently not adequate data from this population to ensure safety with the scope of this protocol. * Any reason the investigator determines may cause noncompliance with study rules or is unfit for receiving treatment. * Currently taking certain medications including antidepressants, stimulants, benzodiazepines, and antipsychotics, antiepileptic (per investigator discretion). * Any positive drug testing from a urine drug test unless medically indicated with a valid prescription. * Those with marijuana/cannabis positive results may retest later if at that time they do not meet criteria for substance abuse at screening and agree to refrain from use for the duration of study participation. Decision to be made by Investigator discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CDRS-R Score From Baseline to Week 4 | Baseline, Week 4 | The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
| Change in CDRS-R Score From Baseline to Week 1 | Baseline, Week 1 | The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
| Change in HAM-D Score From Baseline to Week 2 | Baseline, Week 2 | The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression. |
| Change in CDRS-R Score From Baseline to Week 2 | Baseline, Week 2 | The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
| Change in HAM-D Score From Baseline to Week 3 | Baseline, Week 3 | The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression. |
| Change in CDRS-R Score From Baseline to Week 3 | Baseline, Week 3 | The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
| Change in HAM-D Score From Baseline to Week 4 | Baseline, Week 4 | The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression. |
| Change in HAM-D Score From Baseline to Week 1 | Baseline, Week 1 | The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Completed the Study | Up to Week 5 | Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase). |
| Number of Participants Who Withdrew From the Study | Up to Week 5 | Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase). |
| Durability of Treatment Effect With HAM-D Scores | From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks | Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression. |
| Durability of Treatment Effect With CDRS-R Scores | Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks | Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood. |
| Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks | Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit. |
| Number of Occurrences of Passive Suicidal Ideation | Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks | Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has yes or no answers to assess the likelihood of a subject harming themselves, including yes/no to passive suicidal ideation. Participants indicating a yes response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| iTBS Open Label All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | iTBS Open Label |
|---|---|
| Age, Continuous 13 to 17 year old | 16.2 years |
| Age, Customized Age 13 | 1 Participants |
| Age, Customized Age 17 | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Mean Depression CDRS-R Rating Score | 65.2 Score on an assessment |
| Mean Depression HAM-D Rating Score | 16.8 Score on scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 5 Participants |
| Sex/Gender, Customized Female | 2 Participants |
| Sex/Gender, Customized Male | 2 Participants |
| Sex/Gender, Customized Non-Binary | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Change in CDRS-R Score From Baseline to Week 1
The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: Baseline, Week 1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in CDRS-R Score From Baseline to Week 1 | -9.0 score on a scale |
Primary
Change in CDRS-R Score From Baseline to Week 2
The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: Baseline, Week 2
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in CDRS-R Score From Baseline to Week 2 | -16 score on a scale |
Primary
Change in CDRS-R Score From Baseline to Week 3
The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: Baseline, Week 3
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in CDRS-R Score From Baseline to Week 3 | -11 score on a scale |
Primary
Change in CDRS-R Score From Baseline to Week 4
The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in CDRS-R Score From Baseline to Week 4 | -14 score on a scale |
Primary
Change in HAM-D Score From Baseline to Week 1
The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
Time frame: Baseline, Week 1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in HAM-D Score From Baseline to Week 1 | -7.6 score on a scale |
Primary
Change in HAM-D Score From Baseline to Week 2
The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
Time frame: Baseline, Week 2
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in HAM-D Score From Baseline to Week 2 | -6.2 score on a scale |
Primary
Change in HAM-D Score From Baseline to Week 3
The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
Time frame: Baseline, Week 3
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in HAM-D Score From Baseline to Week 3 | -9.2 score on a scale |
Primary
Change in HAM-D Score From Baseline to Week 4
The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
Time frame: Baseline, Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| iTBS Open Label | Change in HAM-D Score From Baseline to Week 4 | -7.8 score on a scale |
Secondary
Durability of Treatment Effect With CDRS-R Scores
Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| iTBS Open Label | Durability of Treatment Effect With CDRS-R Scores | Follow Up Week 1 | -21 score on a scale |
| iTBS Open Label | Durability of Treatment Effect With CDRS-R Scores | Follow Up Week 4 | -19 score on a scale |
| iTBS Open Label | Durability of Treatment Effect With CDRS-R Scores | Follow Up Week 12 | -23 score on a scale |
Secondary
Durability of Treatment Effect With HAM-D Scores
Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
Time frame: From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| iTBS Open Label | Durability of Treatment Effect With HAM-D Scores | Follow Up Week 4 | -11 score on a scale |
| iTBS Open Label | Durability of Treatment Effect With HAM-D Scores | Follow Up Week 1 | -8.8 score on a scale |
| iTBS Open Label | Durability of Treatment Effect With HAM-D Scores | Follow Up Week 12 | -9.4 score on a scale |
Secondary
Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI
Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit.
Time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Baseline | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Treatment Week 1 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Treatment Week 2 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Treatment Week 3 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Treatment Week 4 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Follow Up Week 1 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Follow Up Week 4 | 0 Occurrences self-harm behavior |
| iTBS Open Label | Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI | Follow Up Week 12 | 0 Occurrences self-harm behavior |
Secondary
Number of Occurrences of Passive Suicidal Ideation
Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has yes or no answers to assess the likelihood of a subject harming themselves, including yes/no to passive suicidal ideation. Participants indicating a yes response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study.
Time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Baseline | 2 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Treatment Week 1 | 2 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Treatment Week 2 | 1 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Treatment Week 3 | 0 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Treatment Week 4 | 2 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Follow Up Week 1 | 2 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Follow Up Week 4 | 0 Occurrences passive suicidal ideation |
| iTBS Open Label | Number of Occurrences of Passive Suicidal Ideation | Follow Up Week 12 | 1 Occurrences passive suicidal ideation |
Secondary
Number of Participants Who Completed the Study
Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).
Time frame: Up to Week 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| iTBS Open Label | Number of Participants Who Completed the Study | 5 Participants |
Secondary
Number of Participants Who Withdrew From the Study
Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).
Time frame: Up to Week 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| iTBS Open Label | Number of Participants Who Withdrew From the Study | 0 Participants |