Clinical trial NCT06310226: Phenotyping Response to Spinal Cord Stimulation in Chronic Low Back Pain
Official title: Characterizing Functional MRI Phenotypes in Response to Spinal Cord Stimulation in Chronic Low Back Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Low Back Pain
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2024-03-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Chronic low back pain (CLBP) is a debilitating condition and costly to treat. Long-term drug treatment often fails due to habituation, breakthrough of pain, or adverse effects of drug treatment. Opioid use to manage this pain has contributed to the opioid epidemic. Spinal cord stimulators have emerged as a promising treatment and reduces reliance on drugs. However, response to spinal cord stimulation (SCS) is unpredictable. It is difficult to predict which patients will respond positively to SCS because the physiological mechanism for treatment responsiveness is unclear. Therefore, the aim of this study is to investigate how spinal cord stimulators affect functional measures in patients with CLBP, including functional MRI, neurophysiology, gait analysis, and questionnaires. The results of this study can lead to the widespread adoption of spinal cord stimulators as a safe and effective therapy for CLBP, reducing the reliance on opioids and mitigating the opioid epidemic's impact.

Detailed description: Electrical stimulation of neural tissues can be effective and reduce reliance on drugs, and epidural spinal cord stimulation (SCS) is often used to treat chronic low back pain (CLBP). Despite a half-century of clinical use, the mechanism of action of SCS remains unclear. Many patients fail to respond to SCS, and lacking a thorough understanding of the biological processes underlying SCS, there are no established predictors of treatment response to SCS. The application of SCS today is dependent on an empirical trial-and-error approach, which is expensive, time consuming, and frustrating for the patient. Even with the advent of improved stimulation technology and novel stimulation strategies (e.g., high frequency, burst stimulation, etc.), device failure rates remain high. CLBP is a multi-faceted process involving abnormal processing in the sensorimotor cortices, prefrontal cortex, insula, thalamus, limbic system, cerebellum, and brainstem nuclei including the periaqueductal gray, locus coeruleus, and dorsal raphe nuclei, all of which function in the context of myriad individual psychosocial factors.

The goal of this study is to develop a quantitative description of the neurophysiological processes associated with the sensation of pain and identify the signature(s) of pain, the neurophysiological pain connectome (NPC), that may guide treatment more effectively. The investigators hypothesize CLBP is marked by a pattern of pathological activity resulting from interactions among different brain networks. The investigators theorize the spatiotemporal patterns of activity among these networks, which are reflected in the NPC, are maladaptive and expressed as abnormal cognitive, affective, and sensorimotor expressions of chronic pain. Because CLBP is a complex disorder, a fundamentally different approach is necessary to assess the many facets of the NPC using comprehensive multi-modal assessments.

Investigators will use: 1. functional and diffusion MRI to quantify brain functional and microstructural connectivity; 2. electroencephalography (EEG); 3. gait kinematics; and 4. electrophysiology (somatosensory evoked potential, SSEP and pain-related evoked potentials, PREPs) to evaluate the neurotransmission of pain. Investigators will then correlate patterns in the NPC with a range of patient-reported outcomes including the domains of the PROMIS questionnaires, and combine this information to generate models based on the patterns in the NPC most closely associated with specific aspects of pain and the patient experience.

Eligibility criteria: Inclusion Criteria:

* Able to give informed consent for participation in the trial and be able to comply with study-related requirements, procedures, and visits
* Male or female, between the ages of 18 and 80 years (inclusive)
* Current self-report of chronic low back pain (pain between the lower posterior margin of the rib cage and the horizontal gluteal fold), which has persisted for \> the past 3 months AND has resulted in pain on \> 50% of days in the past 6 months\* (\*Chronic low back pain criteria as defined by the NIH Pain Consortium Research Task Force (RTF) and BACPAC Minimum Dataset Working Group)
* Already undergoing spinal cord stimulator treatment for chronic low back pain
* Able to use their lower extremities
* Able to tolerate fMRI and neurophysiological evaluation

Exclusion Criteria:

* Significant decision-making incapacity preventing informed consent
* Any medical condition that could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints, as determined by the Investigator.
* Lifetime history of psychiatric disorder (schizophrenia, bipolar disorder with psychotic features, or other psychotic disorder), or current suicidal ideation
* Any stimulation device and/or implant other than a spinal cord stimulator, such as a drug pump, pacemaker, deep brain stimulator (DBS), or sacral nerve stimulator (SNS)
* Life expectancy of less than 1 year
* Pregnant or nursing (if female and sexually active, patient must be using a reliable form of birth control, be surgically sterile, or be at least 2 years post-menopausal)
* Any documented history of substance abuse (narcotics, alcohol, etc.) or substance dependency (not including marijuana use)
* Participation in another clinical trial currently or within the past 30 days
* Current treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (rTMS)
* Conditions that preclude assessing brain function by fMRI: previous head injury, brain surgery, dementia, spinal cord injury, traumatic brain injury, cortical atrophy, serious neurological or medical illness, psychiatric illness, development disability, sensory impairment such as vision and hearing loss, history of birth weight less than 2000 grams and/or gestational age less than 34 weeks)
* MRI compatibility: No major contraindication to MRI (e.g. claustrophobia, pacemaker, vascular stents, metallic ear tubes) and metal implants that would preclude use of MRI
* History of spine surgery with existing instrumentation failure (i.e., broken screws or rods) or pseudarthrosis (lack of fusion) that could be the cause of CLBP
* Any other comorbidity or condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements

Primary outcomes:
measure: Detection of brain connectivity using functional MRI
timeFrame: 1 year
Secondary outcomes:
measure: Detection of brain waves using electroencephalography (EEG)
timeFrame: 1 year
Other outcomes:
measure: Neurological gait kinematics assessment
timeFrame: 1 year
measure: Neurophysiological functional assessment using somatosensory evoked potential (SSEP)
timeFrame: 1 year
measure: Neurophysiological functional assessment using pain-related evoked potential (PREP)
timeFrame: 1 year
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Daniel C Lu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Lily Chau, MD, PhD
role: STUDY_DIRECTOR
References: