Chronic Pain
Conditions
Keywords
pain, chronic pain, fibromyalgia
Brief summary
In this study the investigators aim to assess the correlates of neurophysiological measures (measurement of brain magnetically evoked response) using DELPHI system. The DELPHI system device is a computerized, electromechanical medical device that produces and delivers non-invasive Transcranial Magnetic Stimulation (TMS) fields to induce electrical currents directed at regions of the cerebral cortex and records the resultant Electroencephalogram (EEG) brain electrophysiological response. DELPHI analyzes the TMS Evoked Potential (TEP) and produces quantitative output measures. Objectives include: * To use TMS-evoked EEG measures of brain function in patients with chronic pain using the QuantalX DELPHI system to predict patient specific pain diagnoses using machine learning classification methods. * To evaluate longitudinal associations between TMS-evoked EEG measures and ratings of chronic pain. * To monitor associations between TMS-evoked EEG biomarkers and therapy success for three different classes of medications.
Detailed description
Chronic pain is the leading cause of disability worldwide. Patients with chronic pain have highly variable responses to available treatments, leading to trial-and-error based interventions that delay relief, prolong suffering, and increase reliance on potentially addictive opioid analgesics. This hallmark variability between individual patients is a key barrier to the development of reliable biomarkers for diagnosis and treatment selection. Chronic pain is associated with maladaptive reorganization of brain circuits involved in sensory, emotional, and cognitive aspects of pain. However, specific abnormalities and their relationships to personalized outcomes are unknown. Here, the investigators propose to collect measures of brain network connectivity, excitability, and plasticity using the QuantalX DELPHI-MD (TMS-EEG) system to identify mechanistic biomarkers for patient diagnosis and treatment prognosis. This is a prospective, pilot cohort study. Relationships uncovered during analysis of pilot data will be used to support future experimental research and better characterize specific measures that may be useful to collect in ongoing patient outcome research at UCSF.
Interventions
DEVICEQuantalX DELPHI-MD (TMS-EEG)
Direct Electro-Physiological Imaging medical device (DELPHI-MD), developed by QuantalX Neuroscience, is a neurophysiological assessment system which utilizes a specific TMS-EEG protocol that automatically analyzes specific features of this brain response to reproduce numerical output measures. DELPHI-MD has previously shown to differentiate different healthy age groups, mild dementia and Parkinson's Disease (PD) from age matched healthy control. In addition, DELPHI-MD measures are correlated to white matter microstructural differences in post stroke and TBI patients. This multimodal approach allows for the evaluation of several neurophysiological mechanisms such as cortical reactivity, excitation and inhibition in local and distal regions, effective connectivity, and neural plasticity, characterized as modifications that outlast the stimulation period. The investigators predict that Delphi-MD has the potential to identify features of brain function altered in pain syndromes.
Sponsors
University of California, San Francisco
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male and female participants aged 18-80 with a diagnosis of chronic pain agreeing to participate in all study procedures. To maximize accrual and phenotypic variability in the sample for planned analyses, we include patients meeting ICD-11 criteria for chronic pain, a duration-based parent code for several common, clinically relevant pain conditions. Patients must have pain lasting more than 6 months.
Exclusion criteria
* Neurologic disorders: Dementia, Severe neurocognitive disorder (MoCA \< 22), Severe aphasia, Seizure disorder, certain structural brain lesions (e.g., intracranial mass lesions, neoplasms, hydrocephalus, sequelae of meningitis, MS plaques), cerebral palsy, or complete paralysis * Major psychiatric disorders (e.g., Bipolar Disorder, Schizophrenia), suicidal thoughts * Subjects with any metallic brain implant or fragments (such as shunt, pacemaker, clips, coils, bullet fragments, cochlear implants). * Subjects with any implanted devices activated or controlled by physiological signals and/or ferromagnetic or other magnetic sensitive metals implanted in the head or anywhere within 12 inches/30 cm from the stimulation coil. * Subjects using medications that may alter electroencephalography (EEG) waveforms, including ketamine and benzodiazepines, are eligible to participate, but will be asked to hold these medications 4-8 hours prior to the study visits, as appropriate. * Pregnant or breastfeeding woman.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual analog scores (VAS) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Real time pain intensity and unpleasantness ratings from 0 to 100. |
| TMS-Evoked Potential Amplitude | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | The QuantalX DELPHI (TMS-EEG) system will be used to generate N45 potential amplitudes from the primary motor cortex. The DELPHI System is used for acquisition of physiological signals of Electroencephalography (EEG) from the scalp in response to magnetic stimulation. It consists of a DELPHI amplifier, a computer (workstation), a patient EEG cap, a transcranial magnetic stimulation (TMS) device and Figure 8 stimulation coil. To limit the effect of medications on EEG results, participants will be asked to hold medications known to significantly alter EEG waveforms (including ketamine and benzodiazepines) 4-8 hours prior to the study visits, as appropriate. The device can also generate a range of regional and global metrics of brain excitability (e.g., N100 potential amplitudes), plasticity (e.g., change in N45 amplitude after conditioning pulses), and connectivity (e.g., between region coherence) at each scheduled clinic visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Body Maps | Visit 1(Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | A validated visual representation of the human body allowing patients to record the location and severity of pain. |
| NIH PROMIS questionnaires | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | The NIH PROMIS toolbox contains a host of survey questions tailored to measurement of specific disease states such as pain, global health and function. We will specifically use the Global Health, nociceptive and neuropathic pain (short forms), pain interference (short form), and Patient global impression of change. |
| McGill Pain Questionnaire (MPQ) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | The McGill Pain Questionnaire is a validated measure of multiple domains of pain processing, including sensory and affective pain processing as well as nociceptive and neuropathic pain. Scores range from 0-45 with higher scores indicating more pain. |
| Beck Depression Inventory-II (BDI-II) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Validated measure of clinical depression symptoms to quantify and track mood over time. Scores range from 0-63 with higher scores indicating more depression. |
| World Health Organization Disability Assessment Schedule (WHODAS) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Assessment of functional disability from the WHO to track level of function over time. Scores range from 0-100 with higher scores indicating more disability. |
| Pittsburgh Sleep Quality Index (PSQI) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Validated scale that measures sleep and insomnia symptoms. Scores range from 0-21 with higher scores indicating worse sleep quality. |
| Pain Catastrophizing Scale (PCS) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Validated scale measuring emotional responses to pain to track pain-related symptoms. Scores range from 0-52 with higher scores indicating higher pain catastrophizing. |
| Numerical Rating Scales (NRS) | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Real time pain intensity and unpleasantness ratings from 1 to 10. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Thermal Pain Detection Threshold | Visit 1 (Baseline), Visit 2 (1-3 months after the first visit), Visit 3 (3-6 months), Visit 4 (6-9 months), Visit 5 (9-12 months) | Cold pain and heat pain (°C) thresholds are assessed using Quantitative Sensory Testing (QST) . |
Countries
United States
Outcome results
None listed