- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04556890
Pain and Major Depressive Disorder
Multi-target Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment for Major Depressive Disorder (MDD) and Comorbid Pain
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Doan Ngo, BS
- Phone Number: 310-825-7797
- Email: thucdoanngo@mednet.ucla.edu
Study Contact Backup
- Name: Juliana Corlier, PhD
- Email: jcorlier@ucla.edu
Study Locations
-
-
California
-
Los Angeles, California, United States, 90024
- Recruiting
- UCLA Semel Institute
-
Sub-Investigator:
- Andrew F. Leuchter, MD
-
Principal Investigator:
- Juliana Corlier, PhD
-
Contact:
- THUC-DOAN NGO, BS
- Phone Number: 310-825-7797
- Email: thucdoanngo@mednet.ucla.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- All Subjects must be between 18-75 years of age
- Language: Participants must speak English fluently, as demonstrated by verbal skills sufficient to answer questions at a level that assures adequate understanding of the study
- All subjects must be right-handed
- Must have confirmed diagnosis of moderate Major Depressive Disorder (single or recurrent episode), minimum score of 17 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). No minimal MDD duration necessary for study participation
- Failure to respond to a minimum of 2 trials of antidepressant medication
- Failure to respond from at least two different agent classes
- Accompanied by at least two evidence-based augmentation therapies (Benzodiazepines do not count)
- Must have a trial of psychotherapy known to be effective in the treatment of MDD of an adequate frequency and duration*
- Must have a confirmed FM or ME/CFS diagnoses and moderate pain complaints, minimum score of 15 on the McGill Pain Questionnaire.
- Pain chronicity for at least 3 months prior to study enrollment.
- Subjects are willing and able to adhere to the treatment schedule and required study visits.
Exclusion Criteria:
- Are mentally or legally incapacitated, unable to give informed consent.
- Are pregnant.
- Have an active suicidal intent or plan.
- Have had prior Transcranial Magnetic Stimulation treatment.
- Have an infection or poor skin condition over the scalp where the device will be positioned.
- Have increased risk of seizure because of family history, stroke, or currently use medications that lead to increased risk for seizure.
- Psychotic depression or other acute or chronic psychotic symptoms or disorders (such as schizophrenia, schizophreniform or schizoaffective disorder) in the current depressive episode.
- Neurological conditions that include epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the central nervous system.
- Presence of an implanted metallic and magnetic-sensitive medical device present in the body scan, including but not limited to a cochlear implant, infusion pump, implanted cardioverter defibrillator, pacemaker, vagus nerve stimulator, aneurysm clip, metal prosthesis, or metal aneurysm clips or coils, staples, or stents. (Note: Dental amalgam fillings are not affected by the magnetic field and are acceptable for use with transcranial magnetic stimulation and MRI)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active rTMS/Active iTBS DFPLC/Sham Pain M1
|
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
|
Experimental: Active rTMS/Active iTBS
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent change in depression scores
Time Frame: Through study completion, an average of 6 weeks
|
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.
|
Through study completion, an average of 6 weeks
|
Percent change in pain score
Time Frame: Through study completion, an average of 6 weeks
|
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.
|
Through study completion, an average of 6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Levels of inflammatory markers and transcription factors
Time Frame: Through study completion, average of 6 weeks
|
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
|
Through study completion, average of 6 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20-000530
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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