Multifidus PET Scan Study — MUST  

Low Back Pain Clinical Trial

Official title: A Prospective Single Arm Pilot Study to Investigate the Dynamic Brain and Multifidus Muscle Imaging in Response to Multifidus Stimulation in Patients With Low Back Pain Undergoing Reactiv8 Implant

Status Recruiting

Clinical Trial Summary

The study involves investigating phenotypic changes (ie metabolic activity in brain pain matrix areas, metabolic activity and textural analysis of multifidus muscle) following multifidus stimulation and establishing relationship with the change in pain, functionality and quality of life.

Clinical Trial Description

Multifidus Stimulation via the dorsal ramus is an effective therapy for patients with intractable low back pain. Barts Health has had a positive experience following the implantation of Reactiv8 stimulator in patients with very good success rate in both in Reactiv8 A & B studies. Multifidus stimulation (MS) serves an advantage of functional restoration and neuro-rehabilitation in this difficult group of patients of intractable low back pain, however objective measurement of the multifidus stimulation on supraspinal pathways particularly the changes in higher centres in the brain and in the multifidus muscle itself remains to be characterised.

Dynamic brain imaging in pain (PET/CT scans) Dynamic brain imaging is increasingly used as a research tool to understand the mechanisms of pain and also pain interventions. This is done by using either a functional MRI (fMRI) or Positron Emission Tomography (PET-CT). The implant used for stimulation of the multifidus muscle is not MRI compatible which precludes the use of fMRI. Hence PET-CT is the best available option to investigate the changes in the brain in patients having MS. Functional changes in the brain are identified by the changes in the regional cerebral blood flow (rCBF) as determined by the changes in the distribution of the radioactiove contrast F18- fluorodeoxyglucose (18-FDG) in different areas of the brain.

PET/CT in chronic pain: Chronic pain has been associated with changes in brain structure as well as metabolism especially in the second somatic (SII) regions, insula and anterior cingulate cortex (ACC). Less consistently, changes have also been seen in thalamus and primary somatic area (SI). Sensory discrimination, summation, affect, cognition and attention all seem to influence different areas of the brain there by modulate the patient's pain perception. There is some evidence to suggest that some of these changes may be altered with treatment using either medications or other interventions.

PET in spinal cord stimulation (SCS): There is limited data available on functional neuroimaging following SCS. Nishai et al. conducted FDG PET Scanning in 20 patients (7 CRPS and 13 control) and reported increase in FDG (Flurodeoxyglucose) uptake in left thalamus, anterior cingulate cortex, bilateral insula, dorsolateral prefrontal cortex and bilateral temporal gyrus in six patients where SCS is effective. Similarly Kishima et al reported an increase in blood fIow following SCS in thalamus, orbitofrontal, parietal and prefrontal cortex proportional to the pain relief (larger PET assessed increase in rCBF correlates with decrease in pain intensity) It has been postulated that thalamus activity may relate to whether SCS is effective or not. Recent study comparing Tonic Vs Burst frequencies established differential brain pain matrix areas stimulation with PET-FDG demonstrating the fact of Burst being more associated with medial pathway stimulation, hence perception.

PET in Dorsal Root Ganglion (DRG) stimulation: Barts Health presented the first data on L2-DRG stimulation for low back pain in virgin back patients, with identifiable changes in cereberal metabolic activity in insula, PAG, cerebral cortex following L2-DRG stimulation. Metabolic activity at the target area was measured as standardized uptake value and response to individual pain matrix were demonstrated following L2 stimulation. SUVmax (maximum standardised uptake value) is one of the most common way to measure glucose metabolism. There is evidence that in patients with brain tumours there is increase in cerebral glucose metabolism (measured with SUVmax before and after cervical spinal cord stimulation).

Textural Analysis: Tissue heterogeneity is an important feature associated with adverse tissue biology. Textural analysis has been validated an emerging technique for assessing tissue heterogeneity and quantitative assessments of tissue heterogeneity has the potential to provide non-invasive imaging biomarkers of prognosis and treatment response. Clinical studies have indicated the ability of CT texture analysis (CTTA) to provide independent predictors of survival for patients with malignancies and marker of treatment response. We are utilising the same principal using low dose CT which will be acquired as part of 18F FDG PET-CT image examination. There is no additional radiation exposure for textural analysis. The filtration-histogram method comprises an initial filtration step that highlights image features of a specific size, followed by histogram analysis of the filtered image. The standard descriptors include mean, standard deviation, skewness and kurtosis.

There is still limited data on brain imaging within neuromodulation and there is currently no looking at the PET-CT scan changes following multifidus stimulation. Hence this would be the first study looking into the dynamic brain imaging changes following multifidus stimulation.

This study aims to investigate the dynamic brain imaging in pain using PET scan in patients who have undergone successful Reactiv8 implantation. This may provide us with information on the nature of changes occurring in the brain following multifidus stimulation in the brain pain matrix. Additionally, we aim to measure the changes in the multifidus consistency and metabolic activity following stimulation. This will also hopefully enable us to correlate it with the changes in clinical and health related outcome questionnaires. ;

Related Conditions & MeSH terms

• Back Pain
• Low Back Pain

• NCT number: NCT04327817
• Study type: Interventional
• Source: Barts & The London NHS Trust
• Contact: Vivek Mehta
• Phone: 0203 765 8876
• Email: vivek.mehta@nhs.net
• Status: Recruiting
• Phase: Phase 4
• Start date: August 19, 2021
• Completion date: October 30, 2023