Transcranial Magnetic Stimulation in Patients With Depression and Non-suicidal Self-injury

Study Overview
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Brief Summary
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This clinical trial aims to investigate the effects of Transcranial Magnetic Stimulation (TMS) as an adjunctive treatment for young adult patients with depression and non-suicidal self-injury (NSSI). The main questions this study aims to answer are: Does adjunctive TMS reduce psychiatric symptoms in young adults with major depressive disorder and non-suicidal self-injury? Does adjunctive TMS cause any changes in neuroimaging markers in young adults with major depressive disorder and non-suicidal self-injury? Does adjunctive TMS cause any effects on blood biomarkers in young adults with major depressive disorder and non-suicidal self-injury? Participants in this study will undergo an extensive clinical evaluation, functional neuroimaging tests (MRI and fNIRS), and peripheral blood collection. They will be randomly assigned to one of two interventions: (1) 20 sessions of TMS using the intermittent theta burst stimulation (iTBS) protocol, or (2) 20 sham sessions using a placebo procedure with the TMS equipment. After the 20 sessions, additional clinical assessments, neuroimaging and blood tests will be conducted. The data analysis will compare the two groups in terms of response and remission of internalizing and externalizing psychiatric symptoms, as well as neuroimaging and blood tests outcomes.

Detailed Description
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This comprehensive clinical trial seeks to explore the potential therapeutic benefits of Transcranial Magnetic Stimulation (TMS) when used as an adjunctive treatment for young adult patients grappling with both depression and non-suicidal self-injury (NSSI). The overarching objectives of this study are multifaceted and aim to address critical questions regarding the efficacy and underlying mechanisms of TMS in this particular demographic. The primary research inquiries guiding this investigation are: Psychiatric Symptom Reduction: Does the incorporation of adjunctive TMS lead to a significant reduction in psychiatric symptoms among young adults diagnosed with major depressive disorder and non-suicidal self-injury? Neuroimaging Markers: Does adjunctive TMS induce any discernible changes in neuroimaging markers among young adults with major depressive disorder and non-suicidal self-injury? This involves employing sophisticated functional neuroimaging techniques such as MRI (Magnetic Resonance Imaging) and fNIRS (functional Near-Infrared Spectroscopy). Blood Biomarkers: Are there observable effects on blood biomarkers in young adults with major depressive disorder and non-suicidal self-injury following adjunctive TMS treatment? To investigate these questions, participants enrolled in the study will undergo an extensive and thorough clinical evaluation. Additionally, functional neuroimaging tests, encompassing both MRI and fNIRS, will be administered to gain insights into the neural correlates of TMS treatment. Furthermore, peripheral blood samples will be collected to analyze potential changes in blood biomarkers associated with TMS. The study design incorporates a randomized assignment of participants to one of two interventions: Active TMS Intervention: Participants will undergo 20 sessions of TMS utilizing the intermittent theta burst stimulation (iTBS) protocol. Sham TMS Intervention: A control group will receive 20 sham sessions involving a placebo procedure with the TMS equipment. Following the completion of the intervention phase, participants will undergo additional clinical assessments, neuroimaging, and blood tests to comprehensively evaluate the impact of TMS treatment. The subsequent data analysis will involve a rigorous comparison of the two groups, assessing factors such as the response and remission of internalizing and externalizing psychiatric symptoms, as well as outcomes related to neuroimaging and blood tests.

Official Title
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Transcranial Magnetic Stimulation: Evaluation of Improvement of Transdiagnostic Psychiatric Symptoms and Changes in Functional Neuroiming in Young Adults Patients With Major Depressive Disorder and Non-suicidal Self-injury

Conditions
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Depressive Disorder, Major, Self-Injurious Behavior

Intervention / Treatment
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* Procedure: Transcranial Magnetic Stimulation (TMS)
* Procedure: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current diagnosis of major depressive disorder by the operational criteria of DSM-5 and non-suicidal self-injury behavior, defined by engagement in and intentionally self-inflicted harm to the surface of one's body, likely resulting in bleeding, bruising, or pain (e.g., cutting, burning, puncturing, hitting, excessive rubbing), with the expectation that the injury will only lead to minor or moderate physical harm (i.e., no suicidal intent). (at least one episode in the past year); Depression severity score ≥17 points (moderate depression criteria) on the 17-item Hamilton Depression Rating Scale (HAM-D-17); Currently receiving psychiatric treatment and/or engaged in psychotherapy with a minimum biweekly frequency; Consent to voluntary participation in the study, confirmed by signing the Informed Consent Form; Expressed willingness to comply with all study procedures, including imaging examinations and blood tests, with availability during the study, and to communicate with the study team regarding adverse events and other clinically important information; Commitment to access continuous psychiatric care before and after study completion; In good general health, as evidenced by medical history. Exclusion Criteria: Participants who present pre-established contraindications for undergoing EMT, based on positive responses in the TMS Adult Safety Screen (TASS) questionnaire, such as: cochlear implants, brain stimulators (DBS), electrode implants or aneurysm clips, history of previous seizures, use of pacemakers, presence of implantable defibrillators, brain injury (whether vascular, neoplastic, traumatic, infectious, or metabolic); Patients who present a moderate to severe suicide risk, as determined by clinical evaluation or requiring psychiatric hospitalization during the recruitment or EMT application period; Patients with severe clinical comorbidities or any other reason that impedes self-mobility, preventing attendance at daily EMT sessions; Pregnant patients or those of childbearing age who are sexually active without using contraceptive methods.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 29 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: rTMS Treatment<br>20 sessions of TMS using the intermittent theta burst stimulation (iTBS) protocol | Procedure: Transcranial Magnetic Stimulation (TMS)<br>* The Intermittent Theta Burst Stimulation (iTBS) protocol will be used. This protocol involves bursts of stimulation at the theta frequency range, approximately 5 to 8 Hz. The specific combination utilized combines bursts of pulses at a frequency of 50 Hz, triggered at a rate of 5 Hz. Thus, a burst of 3 pulses is delivered with intervals of 20 ms between them, and this burst is repeated at intervals of 200 ms (i.e., 5 bursts per second). Every second, 15 pulses are delivered.<br>|
| Sham Comparator: Sham Comparator: Sham Treatment<br>20 sham sessions using a placebo procedure with the TMS equipment. | Procedure: Sham<br>* A stimulator with an arm containing a non-functional replica of the stimulation coil will be utilized. The application procedures will be identical to those of the active group, except that the device simulating the stimulation coil will not generate a magnetic field, only producing sound cues mimicking a stimulus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale | Proportion of individuals with a 50% or more score reduction between before and after intervention | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Patient Health Questionnaire-9 | Proportion of individuals with a 50% or more score reduction between before and after intervention | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Montgomery-Asberg Depression Rating Scale | Proportion of individuals with a 50% or more score reduction between before and after intervention | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| fMRI assessed neural network connectivity | Change on functional connectivity | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| fMRI-assessed resting connectivity | Change (e.g. normalization) of baseline network-level deficits. | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Assessment of Self-Mutilation (FASM) | Difference in score between before and after the intervention | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Hamilton Depression Rating Scale | Proportion of individuals with a 50% or more score reduction between before and after intervention | 1, 3 , 6 and 12 months after completion of TMS treatment | 
| Patient Health Questionnaire-9 | Proportion of individuals with a 50% or more score reduction between before and after intervention | 1, 3 , 6 and 12 months after completion of TMS treatment | 
| Montgomery-Asberg Depression Rating Scale | Proportion of individuals with a 50% or more score reduction between before and after intervention | 1, 3 , 6 and 12 months after completion of TMS treatment | 
| fNIRS- assessed changes in blood oxygenation levels in the brain | Changes in blood oxygenation levels in the brain measured by fNIRS (functional near-infrared spectroscopy) to infer neural activity | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Brain-Derived Neurotrophic Factor (BDNF) | Changes in BDNF levels comparing pre- and post-treatment | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Ciliary Neurotrophic Factor (CNTF) | Changes in CNTF levels comparing pre- and post-treatment | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Glial Cell-Derived Neurotrophic Factor (GDNF) | Changes in GDNF levels comparing pre- and post-treatment | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment | 
| Nerve Growth Factor (NGF) | Changes in GDNF levels comparing pre- and post-treatment | Week 1 prior to TMS treatment and week 1 after completion of TMS treatment |