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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Self-Injurious Behavior; Depressive Disorder, Major
• Intervention / Treatment: Procedure: Transcranial Magnetic Stimulation (TMS); Procedure: Sham

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucas Spanemberg, PhD; Phone Number: +555133205900; Email: lucas.spanemberg@pucrs.br

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Recruiting
      • Instituto do Cerebro do Rio Grande do Sul
      • Contact: Karoline Flach; Phone Number: +555133205900

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: rTMS Treatment; 20 sessions of TMS using the intermittent theta burst stimulation (iTBS) protocol	Procedure: Transcranial Magnetic Stimulation (TMS); 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.
Sham Comparator: Sham Comparator: Sham Treatment; 20 sham sessions using a placebo procedure with the TMS equipment.	Procedure: Sham; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brain Institute of Rio Grande do Sul
• Investigators: Principal Investigator: Lucas Spanemberg, PhD, Instituto do Cerebro do Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Self-Injurious Behavior
• Other Study ID Numbers: 908; INSCER908 (Other Identifier: BrainInstitute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No