Relationship of Peripheral Inflammatory and Neuroprotective Biomarkers With Response to Intermittent Theta Burst Stimulation in Treatment-Resistant Depression
Recruiting · NCT07673913 · Interventional (participants receive a specific treatment)
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Treatment-resistant depression (TRD) is a major clinical challenge affecting a substantial proportion of patients with major depressive disorder who do not adequately respond to conventional antidepressant treatments. Intermittent theta burst stimulation (iTBS), a non-invasive neuromodulation technique targeting the left dorsolateral prefrontal cortex, has emerged as an effective treatment option for these patients. However, the biological mechanisms underlying treatment response remain poorly understood. This single-center, prospective, investigator-initiated clinical study aims to investigate the effects of iTBS on clinical symptoms, executive functions, and peripheral inflammatory and neuroprotective biomarkers in patients with treatment-resistant depression. Fifty patients with treatment-resistant depression and fifty healthy control participants will be enrolled. Patients will receive active iTBS treatment for four weeks (20 sessions), while healthy controls will undergo baseline clinical, cognitive, and biological assessments without receiving any intervention. Clinical outcomes will be evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Patient Health Questionnaire-9 (PHQ-9), Clinical Global Impression (CGI), and Insomnia Severity Index (ISI). Executive functions will be assessed using the Wisconsin Card Sorting Test, Trail Making Test A and B, and verbal fluency tests. Peripheral blood samples will be collected before and after treatment to measure inflammatory, neuroplasticity, and neuroprotective biomarkers, including IL-1β, IL-6, IL-10, TNF-α, high-sensitivity C-reactive protein (hs-CRP), brain-derived neurotrophic factor (BDNF), apolipoprotein D (APOD), serum amyloid A1 (SAA1), and serum amyloid A2 (SAA2). Gene expression analyses will also be performed using quantitative polymerase chain reaction (qPCR). The study aims to identify biological mechanisms associated with iTBS treatment response and to explore potential biomarkers that may predict clinical improvement in patients with treatment-resistant depression. The findings may contribute to the development of personalized neuromodulation strategies and biomarker-guided treatment approaches for depression.
Who can take part
Inclusion criteria
- Treatment-Resistant Depression Group:
- Age between 18 and 55 years. Male or female participants. Diagnosis of Major Depressive Disorder according to DSM-5-TR criteria. Inadequate response to at least two antidepressant treatments administered at adequate doses and durations.
- Eligible for transcranial magnetic stimulation (TMS) treatment. Able and willing to provide written informed consent. Able to complete neuropsychological assessments. Able to attend study visits and complete the treatment protocol.
- Healthy Control Group:
- Age between 18 and 55 years. Male or female participants. No current DSM-5-TR psychiatric disorder. Able and willing to provide written informed consent. Able to complete neuropsychological assessments.
Exclusion criteria
- Schizophrenia, bipolar disorder, organic mental disorders, or other major psychiatric disorders.
- History of epilepsy, brain tumor, severe head trauma, or significant neurological disease.
- Any contraindication to TMS. Presence of intracranial metal implants, cardiac pacemakers, cochlear implants, or other incompatible implanted devices.
- Active infection. Autoimmune disease or chronic inflammatory disease. Electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation within the previous 5 years.
- Previous intravenous or intranasal ketamine treatment. Pregnancy or breastfeeding. Active alcohol or substance use disorder. Inability to comply with study procedures. Inability to tolerate the iTBS protocol. Withdrawal of informed consent at any stage of the study.
Where it is running
2 locations listed.
- Gulhane Training and Research Hospital - Ankara, Turkey (Türkiye)
- Gulhane Training and Research Hospital - Ankara, Ankara, Turkey (Türkiye)