TMS-EEG Biomarkers for Chronic Pain

NCT07116278 | Active Not Recruiting FDA Device

• 1 other identifier: 23-40427
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Pain

Keywords

pain; chronic pain; fibromyalgia

Outcome Measures

Primary Outcomes (2)

• TMS-Evoked Potential Amplitude

  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.

  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)

• Visual analog scores (VAS)

  Real time pain intensity and unpleasantness ratings from 0 to 100.

  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)

Secondary Outcomes (8)

• 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)

• 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)

• 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)

• 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)

• 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)

Other Outcomes (1)

• 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)

Study Arms (1)

Longitudinal TMS-EEG

OTHER

Each visit will involve completion of the TMS-EEG intervention.

Device: QuantalX DELPHI-MD (TMS-EEG)

Interventions

QuantalX DELPHI-MD (TMS-EEG) DEVICE

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.

Longitudinal TMS-EEG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF

San Francisco, California, 94107, United States

Location

Related Publications (4)

• Zifman N, Levy-Lamdan O, Suzin G, Efrati S, Tanne D, Fogel H, Dolev I. Introducing a Novel Approach for Evaluation and Monitoring of Brain Health Across Life Span Using Direct Non-invasive Brain Network Electrophysiology. Front Aging Neurosci. 2019 Sep 9;11:248. doi: 10.3389/fnagi.2019.00248. eCollection 2019.

  PMID: 31551761 BACKGROUND

• Maidan I, Zifman N, Hausdorff JM, Giladi N, Levy-Lamdan O, Mirelman A. A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease. Parkinsonism Relat Disord. 2021 Aug;89:28-33. doi: 10.1016/j.parkreldis.2021.06.018. Epub 2021 Jun 29.

  PMID: 34216938 BACKGROUND

• Levy-Lamdan O, Zifman N, Sasson E, Efrati S, Hack DC, Tanne D, Dolev I, Fogel H. Evaluation of White Matter Integrity Utilizing the DELPHI (TMS-EEG) System. Front Neurosci. 2020 Dec 21;14:589107. doi: 10.3389/fnins.2020.589107. eCollection 2020.

  PMID: 33408607 BACKGROUND

• Fogel H, Levy-Lamdan O, Zifman N, Hiller T, Efrati S, Suzin G, Hack DC, Dolev I, Tanne D. Brain Network Integrity Changes in Subjective Cognitive Decline: A Possible Physiological Biomarker of Dementia. Front Neurol. 2021 Aug 30;12:699014. doi: 10.3389/fneur.2021.699014. eCollection 2021.

  PMID: 34526957 BACKGROUND

MeSH Terms

Conditions

Chronic Pain; Pain; Fibromyalgia

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Julian Motzkin, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2025
• First Posted: August 11, 2025
• Study Start: November 18, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: All data will be deposited to OpenNeuro and OSF within 6 months of the final publication resulting from these data.
• Access Criteria: To request access of the data, researchers will use the standard processes at OSF, which involve contacting the study author for use permission. Data can be accessed freely on UCSF MyResearch.

Locations

US (1)