Detection of EEG-Based Biomarkers of Chronic Low Back Pain

Characterization of Longitudinal EEG Biomarkers in Chronic Low Back Pain

Chronic low back pain (CLBP) is a pervasive disorder affecting up to one-fifth of adults globally and is the single greatest cause of disability worldwide. Despite the high prevalence and detrimental impact of CLBP, its treatments and mechanisms remain largely unclear. Biomarkers that predict symptom progression in CLBP support precision-based treatments and ultimately aid in reducing suffering. Longitudinal brain-based resting-state neuroimaging of patients with CLBP has revealed neural networks that predict pain chronification and its symptom progression. Although early findings suggest that measurements of brain networks can lead to the development of prognostic biomarkers, the predictive ability of these models is strongest for short-term follow-up. Measurements of different neural systems may provide additional benefits with better predictive power.

Emotional and cognitive dysfunction is common in CLBP, occurring at the behavioral and cerebral level, presenting a unique opportunity to detect prognostic brain-based biomarkers. Likewise, improvements in electroencephalogram (EEG) neuroimaging strategies have led to increased spatial resolution, enabling researchers to overcome the limitations of classically used neuroimaging modalities (e.g., magnetic resonance imaging [MRI] and functional MRI), such as high cost and limited accessibility. Using longitudinal EEG, this patient-oriented research project will provide a comprehensive neural picture of emotional, cognitive, and resting-state networks in patients with CLBP, which will aid in predicting symptom progression in CLBP. Through this award, the investigators will use modern EEG source analysis strategies to track biomarkers at baseline and 3- and 6-month follow-ups and their covariance with markers for pain and emotional and cognitive dysfunction. In Aim 1, the investigators will identify and characterize differences in resting-state, emotional, and cognitive networks between patients with CLPB and age/sex-matched controls. In Aim 2, the investigators will identify within-subject changes across time and their relationship with clinical symptoms. In Aim 3, as an exploratory aim, the investigators will apply machine- and deep-learning strategies to detect a comprehensive signature of CLBP using EEG features from resting-state, emotional, and cognitive networks.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Chronic Low-back Pain
• Intervention / Treatment: Behavioral: Resting State EEG; Behavioral: Picture Viewing EEG; Behavioral: Stop Signal EEG

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Omar Altirkawi; Phone Number: 650-724-8426; Email: omar97@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford's Systems and Neuroscience Pain Lab
      • Contact: Omar Altirkawi; Phone Number: 650-724-8426; Email: omar97@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Current diagnosis of Chronic Low Back Pain

Exclusion Criteria:

• Current diagnosis of cancer
• Severe psychiatric conditions
• Pending personal litigation relating to an injury or receiving workers' compensation benefits
• Being a non-English speaker.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; All participants will complete all interventions

Behavioral: Resting State EEG; During this intervention, participants will be asked to not think about anything in particular while EEG is recorded. Resting state will be conducted with either the participants having their eyes open, or eyes closed.; Behavioral: Picture Viewing EEG; During this intervention, participants will view emotionally charged pictures for a short period of time. Afterwards, participants will be asked to rate their emotional reactions to the pictures. EEG will be recorded during this intervention.; Behavioral: Stop Signal EEG; During this intervention, participants will be asked to respond quickly to a visual stimulus with a button press. At times, participants will be asked to inhibit their responses. EEG will be recorded during this intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG resting state functional connectivity changes from baseline	Within subjects change in resting state functional connectivity from baseline to each follow up point.	Baseline, 3-month and 6-month follow-ups
EEG late positive potential changes from baseline	Within subjects change in late positive potential from baseline to each follow up point.	Baseline, 3-month and 6-month follow-ups
EEG error related negativity changes from baseline	Within subjects change in error related negativity from baseline to each follow up point.	Baseline, 3-month and 6-month follow-ups
Pain Intensity changes from baseline as assessed by the PROMIS current, 7 day maximal and 7 day average	Within subjects change in pain intensity from baseline to each follow up point. Pain intensity measures are 0-10 range with larger numbers indicating more pain	Baseline, 3-month and 6-month follow-ups

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological changes from baseline as assessed by the NIH toolbox	Within subjects change in metrics of fluid and crystallized intelligence from baseline to each follow up point	Baseline, 3-month and 6-month follow-ups

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain
• Other Study ID Numbers: 71778; 1K23AR083171-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will support requests for data sharing in a timely manner. Prior to sharing data, the data will be redacted of all personal identifiers to prevent subject identification.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No