An interventional study of Active rTMS/Active iTBS DFPLC/Sham Pain M1 and Active rTMS/Active iTBS in Major Depressive Disorder and Chronic Pain, sponsored by University of California, Los Angeles. Recruiting at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by University of California, Los Angeles · Not applicable, Interventional, and Treatment
This study will examine the effects of brain stimulation on pain symptoms associated with Major depressive disorder. This study will enroll 54 Subjects. Study subjects will be asked to complete surveys about their mood and well-being, 2 blood draws, 2 MRIs, 3 electroencephalograms, and receive 30 treatments of blinded transcranial magnetic stimulation. There is no control group as all subjects will receive some form of active treatment. Subjects are required to participate in 30-33 study visits and volunteer 40 hours of their time. Compensation for this study is $150 for completing all study activities.
The main objective of the proposed study is to evaluate the therapeutic effect of multi-site repetitive Transcranial Magnetic Stimulation (rTMS) on chronic pain and inflammatory responses in Major Depressive Disorder (MDD). MDD is the leading cause of disability worldwide. One reason for the extraordinarily high burden of depression is painful somatic symptoms: more than half of MDD patients complain of moderate to severe pain that is associated with interference in function and unemployment and which can lead to opioid use disorder. The neuro-immune interaction is increasingly understood as the underlying mechanism of this comorbidity. Sustained psychosocial stress can cause a lasting increase in systemic inflammation, which may be a key mediator of chronic pain and depression. Pro-inflammatory cytokines have been linked to the dysregulation of signaling in the mesocorticolimbic system and affect-related circuits present in both chronic pain and depression. Meta-analyses have identified higher CRP, IL6, and TNFa among depressed patients. Additionally, CRP was found to be increasingly higher with higher number failed treatment trials, suggesting that treatment resistant depression (TRD) patients who qualify for rTMS tend to have higher inflammation than those who respond to pharmacological antidepressant treatment [6]. Further, baseline levels of transcriptional control pathways (TCP) related to immune or sympathetic activation and glucocorticoid insensitivity mediate experimentally induced depressed mood. Even though the inflammatory reaction may originate in the periphery, downstream effects can result in neuroinflammation and changes in neural network function through several immune-to-brain signaling pathways. Previous research has shown that functional connectivity between DLPFC and anterior cingulate cortex (ACC) also mediates neuroinflammation levels in ACC, and which was linked to depressive scores in chronic pain patients [8]. rTMS to the left dorsolateral prefrontal cortex (DLPFC) is a non-invasive neuromodulation technique that has proven clinical efficacy for MDD and rTMS to primary motor cortex (M1) has been demonstrated to reduce chronic pain, including fibromyalgia, neuropathic pain, headache and regional pain].
Based on these findings, the investigators hypothesize that combined rTMS to depression and pain targets will reduce both depressive and pain symptoms and will also result in an effective reduction of systemic inflammation. The proposed research will examine the effects of 30 neuro-navigated sessions of active vs. sham rTMS using 2 conditions: A) active rTMS at DLPFC and sham at M1; B) active rTMS at DLPFC and M1. This design will help to dissociate the impact of an antidepressant response on pain reduction (condition A), or whether the combined treatment (condition B) will result in a synergetic effect. The investigators will focus on pain types related to inflammation including fibromyalgia (FM) and ME/CFS, whose symptomatic profiles are closely overlapping with those of MDD and may thus preferentially respond to rTMS.
The investigators will combine the analysis of circulating pro-inflammatory cytokines with transcriptomic analyses, which may be even more sensitive to short-term changes. Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data will be used to assess biomarkers and mechanisms of action (MOA) of successful rTMS treatment for pain. The conceptualization of pain treatment in MDD at the brain network and systemic levels makes this study a highly innovative approach to neuropsychiatric research.
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This study's planned enrollment of 54 is below the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
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Exclusion Criteria:
Device: Active rTMS/Active iTBS DFPLC/Sham Pain M1
Device: Active rTMS/Active iTBS
Active rTMS treatment for depression (600 pulses of active intermittent theta burst (iTBS) administrated at 120% MT to the left DLPFC) and sham treatment for pain at M1
Active rTMS treatment for both, depression and pain (600 pulses of iTBS to left DLPFC followed by 600 iTBS + 1500 pulses of 10 Hz to M1
Percent change in depression scores
Inventory of Depressive symptoms- Self (IDS-SR) scores will be analyzed as the primary outcome measure. The IDS-SR is a 30-item scale that measures various symptoms of depression. Each item is scored between 0-4. Severity of depression is associated with a higher score with scores ranging from 0 to 84.
Time frame: Through study completion, an average of 6 weeks
Percent change in pain score
McGill Pain questionnaire (MPQ) will be analyzed as the secondary outcome. MPQ is a self-reporting measure of pain used for patients with a number of diagnoses. It assesses both quality and intensity of subjective pain and effectiveness of an intervention. Scoring ranges from 0 to 78. A higher score is associated with greater pain.
Time frame: Through study completion, an average of 6 weeks
Levels of inflammatory markers and transcription factors
Specimen will be processed and compared based on levels of pro-inflammatory cytokines and transcription factors (TF) related to immune activation, sympathetic activation and glucocorticoid insensitivity
Time frame: Through study completion, average of 6 weeks
Plan to share: No
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University of California, Los Angeles