Clinical trial NCT06110585: Transcranial Magnetic Stimulation in Patients With Depression and Non-suicidal Self-injury
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depressive Disorder, Major
Self-Injurious Behavior
Lead sponsor: Brain Institute of Rio Grande do Sul
Sponsor class: NETWORK
First posted: 2023-10-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 29
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Patient Health Questionnaire-9
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: fMRI assessed neural network connectivity
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: fMRI-assessed resting connectivity
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
Secondary outcomes:
measure: Functional Assessment of Self-Mutilation (FASM)
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Hamilton Depression Rating Scale
timeFrame: 1, 3 , 6 and 12 months after completion of TMS treatment
measure: Patient Health Questionnaire-9
timeFrame: 1, 3 , 6 and 12 months after completion of TMS treatment
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: 1, 3 , 6 and 12 months after completion of TMS treatment
measure: fNIRS- assessed changes in blood oxygenation levels in the brain
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Brain-Derived Neurotrophic Factor (BDNF)
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Ciliary Neurotrophic Factor (CNTF)
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Glial Cell-Derived Neurotrophic Factor (GDNF)
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
measure: Nerve Growth Factor (NGF)
timeFrame: Week 1 prior to TMS treatment and week 1 after completion of TMS treatment
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Instituto do Cérebro do Rio Grande do Sul
state: RS
Study officials:
affiliation: Instituto do Cérebro do Rio Grande do Sul
name: Lucas Spanemberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: