Clinical trial NCT04485455: iTBS for Adolescent Depression: An Open Label Study Evaluating Safety and Efficacy of Treatment
Official title: Open Label Study of the Efficacy, Durability, Safety and Feasibility of Intermittent Theta Burst Stimulation (iTBS) in Adolescents With Major Depressive Disorder: Effect Duration, Suicidality, and Non-Suicidal Self Injurious Behavior
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Keywords: Adolescent Depression
Teen Depression
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2020-07-24
Enrollment: 5
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in HAM-D Score From Baseline to Week 1
timeFrame: Baseline, Week 1
measure: Change in CDRS-R Score From Baseline to Week 1
timeFrame: Baseline, Week 1
measure: Change in HAM-D Score From Baseline to Week 2
timeFrame: Baseline, Week 2
measure: Change in CDRS-R Score From Baseline to Week 2
timeFrame: Baseline, Week 2
measure: Change in HAM-D Score From Baseline to Week 3
timeFrame: Baseline, Week 3
measure: Change in CDRS-R Score From Baseline to Week 3
timeFrame: Baseline, Week 3
measure: Change in HAM-D Score From Baseline to Week 4
timeFrame: Baseline, Week 4
measure: Change in CDRS-R Score From Baseline to Week 4
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Number of Occurrences of Passive Suicidal Ideation
timeFrame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
measure: Number of Participants Who Completed the Study
timeFrame: Up to Week 5
measure: Number of Participants Who Withdrew From the Study
timeFrame: Up to Week 5
measure: Durability of Treatment Effect With HAM-D Scores
timeFrame: From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
measure: Durability of Treatment Effect With CDRS-R Scores
timeFrame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
measure: Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI
timeFrame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill-Psychiatry Outpatient Clinic
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Shahzad Ali, MD
role: PRINCIPAL_INVESTIGATOR
References: