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

Depressive Disorder, Major Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06110585
• Other study ID #: 908
• Secondary ID: INSCER908
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: February 28, 2025

Study information

• Verified date: October 2023
• Source: Brain Institute of Rio Grande do Sul
• Contact: Lucas Spanemberg, PhD
• Phone: +555133205900
• Email: lucas.spanemberg[@]pucrs.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 28, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 29 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Self-Injurious Behavior

Intervention

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
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.

Locations

Country	Name	City	State
Brazil	Instituto do Cérebro do Rio Grande do Sul	Porto Alegre	RS

Sponsors (1)

Lead Sponsor	Collaborator
Brain Institute of Rio Grande do Sul

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	fMRI assessed neural network connectivity	Change on functional connectivity	Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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