aiTBS for Relieving NSSI in Depressive Patients

Study Overview
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Brief Summary
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Repetitive transcranial magnetic stimulation (rTMS) has been successfully used to help patients with treatment resistant depression. However, its role in alleviating self injuries without suicidal ideation remained uncertain. This trial will compare the effectiveness of active accelerated intermittent theta burst stimulation (aiTBS) rTMS to a placebo control on non-suicidal self injury (NSSI) in patients with unipolar disorder and bipolar disorder.

Detailed Description
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The study will evaluate the efficacy and safety of aiTBS in unipolar and bipolar depressive patients with NSSI or suicidal thoughts and behaviors by measuring changes in clinical ratings at baseline, after all the treatments, and 2 weeks, 4 weeks after treatment. 60 inpatients will be randomized to receive active or sham interventions administered to the left dorso-lateral prefrontal cortex. The treatment will apply active aiTBS rTMS involving 1800 pulses (9 minutes), 5x daily at 60 minutes intervals for 5 days. Changes in mood and sleep from baseline to the end of the study will be measured with The Hamilton Rating Scale for Depression-17 item (HAM-D17), Hamilton Anxiety Scale (HAMA), Young's Mania Scale (YMRS), and Pittsburgh Sleep Quality Index (PSQI) . Non-suicidal self injury will be assessed by the Deliberate Self-Harm Inventory (DSHI) and the Ottawa self-injury inventory (OSI). Suicidal ideation and behaviors assessments include Beck Suicidal Scale Inventory (BSI), the Ottawa self-injury inventory (OSI) and several questions from Self-Injurious Thoughts and Behaviors Interview - Revised (SITBI-R). Improvement of cognitive dysfunction could be measured by Barratt Impulsiveness Scale-11 (BIS-11), near infrared spectroscopy (fNIRS). Treatment Emergent Symptom Scale (TESS) would be used to eliminate side effects of combined drugs at baseline and the adverse event record form (AERF) will be used to appraise the safety of aiTBS treatment using these parameters. To record the change in sensitivity to pain and examine the tolerability of the treatment for these participants, visual analogue scale (VAS) is employed after completing 5 sessions treatment every day.

Official Title
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Accelerated Intermittent Theta Burst Stimulation for the Treatment of Non-suicidal Self-injury in Patients With Unipolar Depression and Bipolar Depression: a Sham-controlled Study

Conditions
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Major Depressive Disorder, Bipolar Depression

Intervention / Treatment
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* Device: Active iTBS
* Device: Sham iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of DSM-5 criteria for current major depressive disorder (MDD) or bipolar disorder (BD) will be required for study entry. Ages between 12 and 18 years At least 1 caregivers to supervise the patient within 3 month. A score of greater than 17 on the HAM-D17. Occurrences of self injury behavior consistent with the DSM-5 criteria of NSSI more than 3 times in a month. Willingness to participate in the study and sign informed consents Exclusion Criteria: Substance abusers such as psychoactive drugs or alcohol. Severe physical disability and unable to complete follow-up. Comorbid other major mental illnesses that meet the DSM-5 criteria, such as schizophrenia, mental retardation, dementia, severe cognitive impairment, attention deficit hyperactivity disorder, etc. Currently in a manic episode, YMRS>12; rapid-cycling bipolar disorder, bipolar disorder with mixed features. Suffering from any severe physical disease, neurological disease, traumatic brain injury, etc, that affects the structure or function of the brain in the lifetime. Unable to read, understand and complete the assessment or to cooperate with the investigators. Any implants covering a pacemaker, metallic or magnetic objects in the body, or other conditions not suitable for rTMS. A history or family history of epilepsy and other contraindications to TMS. Daily use of benzodiazepines (more than 2mg/d), theophylline, stimulants such as methylphenidate, anticonvulsants, bupropion, etc. Those who have received systematic psychotherapy (interpersonal relationship therapy, dynamic therapy, cognitive behavioral therapy) within 3 months before baseline. Other examination abnormalities considered to be inappropriate by investigators.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled clinical trial testing iTBS versus sham
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active stimulation<br>Active Intermittent theta burst stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. | Device: Active iTBS<br>* MagPro X100<br>|
| Sham Comparator: Sham stimulation<br>Sham stimulation to the dorsolateral prefrontal cortex; 5 sessions per day, for 5 days. | Device: Sham iTBS<br>* MagPro X100<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Deliberate Self-Harm Inventory (DSHI) | Containing one subscale ranging from 0 to 57 to measure the frequencies of NSSI behavior and one subscale ranging from 0 to 76 to measure the severity of NSSI behavior. | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pittsburgh Sleep Quality Index (PSQI) | Range from 0-21, higher score indicates severe poorer sleep quality | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in Hamilton Anxiety Scale (HAMA) | Range from 0-56, higher score indicates more severe symptoms | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in Young's Mania Scale (YMRS) | Range from 0-60, higher score indicates more severe symptoms | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in Barratt Impulsiveness Scale-11 (BIS-11) | Range from 26-104, higher score indicates higher impulsivity | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in cerebral blood flow of PFC through Near Infrared Spectroscopy (fNIRS) | Measuring the hemoglobin concentration of cerebral cortex during resting state and verbal fluency test. | Baseline, after 5 treatment days | 
| Changes in the 17-item Hamilton Rating Scale for Depression (HAMD-17) | This will be measured as both a continuous variable (scores on HAMD-17 ) and a categorical one (i.e. the response rates of >50% reduction from baseline HAMD-17 and remission rates defined as HAMD-17 <7). | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in Beck Suicidal Scale Inventory (BSI) | Range from 0- 38, higher score indicates more severe suicide ideation. | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in The Clinical Global Impression (CGI) | Measuring the symptom severity, overall improvement, and therapeutic response to intervention. | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in the subscale of addiction of NSSI from OSI (Ottawa self-injury inventory) | Range from 0- 28, higher score indicates higher addiction. | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in number of occurrences of Non-Suicidal Self Injurious ideation Through SITBI-R | The frequency of NSSI thoughts during the latest week | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in likelihood of future Non-Suicidal Self Injury Through SITBI-R | Range from 0-4, higher score indicates more likelihood to conduct NSSI in the future | Baseline, after 5 treatment days, 2 week and 4 week post-treatment | 
| Changes in the Deliberate Self-Harm Inventory-ideation (DSHI-ideation) | Range from 0 to 57 to measure the frequency of NSSI ideation | Baseline, after 5 treatment days, 2 week and 4 week post-treatment |