Brain Connectivity Changes With Spinal Cord Stimulation and Treatment of Chronic Pain: A Resting State NIRS/EEG Study

Neuropathic Pain Clinical Trial

Official title:

Brain Connectivity Changes With Spinal Cord Stimulation Treatment of Chronic Pain: A Resting State NIRS/EEG Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05811312
• Other study ID #: F4389-P
• Status: Recruiting
• Start date: July 1, 2023
• Est. completion date: July 1, 2025

Study information

• Verified date: August 2023
• Source: VA Office of Research and Development
• Contact: Cheryl Dudek
• Phone: (216) 679-3800
• Email: cheryl.dudek[@]va.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to assess how use of spinal cord stimulation for the treatment of chronic pain impacts brain structure and function. The investigators will use a non-invasive neuroimaging technique called resting state Near Infrared Spectroscopy and Electroencephalography (rs-fNIRS/EEG). The investigators will enroll Veterans who are currently receiving care at the Medical Center and who are either long term users of SCS for the treatment of their chronic pain or being evaluated for use of SCS to treat their pain.

Description:

Chronic pain is a complex neurological disease that adversely impacts function and quality of life. Brain structure and function are altered when an individual is in the chronic pain state. Furthermore, chronic pain is associated with disruptions in functional brain connectivity. Spinal cord stimulation (SCS) is a clinically available non-pharmacological therapy that is used in the management of chronic pain. Although SCS is effective for many, there are individuals who do not benefit. Therefore, in order to better understand brain mechanisms that underlie SCS treatment of chronic pain and to develop brain biomarkers of SCS efficacy, the investigators propose to evaluate functional brain changes in response to SCS. Finding a brain signature of pain relief in response to SCS would improve understanding of how SCS alleviates chronic pain and may help to identify those most likely to respond. The main objective of this study is to assess changes in brain connectivity in response to SCS in individuals with chronic neuropathic pain. The investigators will study two cohorts: Cohort 1 - na�ve to SCS patients who are undergoing SCS trial period; Cohort 1 - long-term SCS users ( 6 months post implantation). The investigators aim to identify neurophysiological brain signatures of pain relief in these two populations using resting state Near Infrared Spectroscopy and Electroencephalography (rs-fNIRS/EEG). Study Design: The investigators will enroll Veterans with refractory chronic neuropathic pain who are currently receiving clinical care within the medical center. Cohort 1: Individuals with chronic neuropathic pain who are na�ve to SCS and were selected for SCS trial period as part of their clinical care will participate in two study visits: before the beginning of the SCS trial and the end of the trial period. Data collection will be consistent across all data collection timepoints (T1 - T3) and include rs-fNIRS/EEG and clinical pain measures. Cohort 2: Participants with effective implanted SCS 6 months will participate in three study visits conducted 24-48 hours apart. Data will be collected during SCS use and following an SCS washout period. Data collection will be consistent across all data collection timepoints(T1-T4) and include rs-fNIRS/EEG and clinical pain measures. Both cohorts will receive paresthesia based SCS. AIM 1 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief during the SCS trial period for patients with chronic neuropathic pain who are na�ve to SCS. AIM 2 is to characterize neurophysiological (rs-fNIRS/EEG) brain signature of pain relief in patients with chronic neuropathic pain who have utilized SCS for 6 months. Outcome Measures to address both aims include rs-functional connectivity (rs-fNIRS/EEG); and a composite clinical pain assessment that will include Numeric Pain Rating Scale (NPRS), Patient Reported Outcomes Measurement Information System-29 profile v2.1(PROMIS-29); EQ-5D-5L; Patient Global Impression of Change (PGIC); painDetect; and activity monitoring. Significance: Studying changes in brain connectivity in response to SCS will provide insight into the treatment mechanism of SCS. Use of neuroimaging methods such as rs-fNIRS/EEG that can be easily applied in the clinical setting to further refine patient selection for SCS may improve outcome in SCS therapy. This grant will provide preliminary data for future studies aimed at developing biomarkers of pain-relief with SCS treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years of age and a US veteran

• Diagnosis of chronic neuropathic pain.

• Current patient at Cleveland VA Medical Center receiving care via Pain Medicine Center.

• Current user of tonic parasthesia-based SCS (pain relief 50% according to NPRS) or undergoing trial SCS period as part of clinical care.

• Able to provide informed consent.

• Medically and psychologically stable.

Exclusion Criteria:

• Metal in the skull or deformity of the skull

• Pregnancy or pregnancy planning during the study period.

• Unable to provide informed consent.

Related Conditions & MeSH terms

• Chronic Pain
• Neuralgia
• Neuropathic Pain

Locations

Country	Name	City	State
United States	Louis Stokes VA Medical Center, Cleveland, OH	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in resting state Functional Connectivity	resting state functional connectivity will be evaluated with fNIRS and EEG. We will model "response to SCS" with changes in resting state functional connectivity between five bilateral cortical regions. These regions are the medial prefrontal cortex (mPF), dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), primary sensory cortex (S1), and posterior parietal cortex (PPC). Brain connectivity will be evaluated with fNIRS and EEG. Prefrontal medial cortex and posterior temporoparietal regions are good proxy measures of DMN activity using fNIRS.45-47 DMN nodes include additional deep brain structures18 but they are outside the field of view for most fNIRS instruments. We will evaluate S1 for its role in pain processing, M1 for its contribution to pain sensation via thalamic inhibition, and DLPFC for its known role in cognitive and affective pain processing.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Primary	Change in Numeric pain rating scale	NPRS measures pain intensity. Individuals select a number on a 0-10 scale that best describes the intensity of their current, best and worst pain levels; 0-10 scale, with 10 indicating maximum pain.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Secondary	Change in EQ-5D-5L	EQ-5D-5L is a 5-domain health-related quality of life measure; -0.59-1.00 scale, with 1=best health state.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Secondary	Change in Patients Global Impression of Change (PGIC)	Patient's Global Impression of Change (PGIC) is a 7-point scale to assess patient perception of change in response to treatment. 1=no change, and 7=a great deal better.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Secondary	Change in PROMIS-29 Profile v2.1	PROMIS-29 Profile v2.1 is a questionnaire covering 7 domains including physical function, anxiety, depression, fatigue, sleep disturbance, participation in social roles/activities, and pain interference. Higher T-scores indicate more severity/worse health.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Secondary	Change in PainDetect	PainDetect is a self-report measure that was developed to assess neuropathic pain in adults with low back pain; 0-38 points, with higher score more indicative of neuropathic pain.	Cohort 1: day 1 and between days 5-9; Cohort 2: day 1 and between days 3-6
Secondary	Change in Actigraphy	Activity monitoring using a wrist-worn device (Actigraphy) will be utilized to monitor real-life activity and sleep patterns; calculating % time active versus sedentary.	Cohort 1-between 5 and 9 days; Cohort 2-between 3-6 days.