Neurophysiological Effects of Medication Tapering During Treatment With Spinal Cord Stimulation

Official title

Assessment of Neurophysiological Effects of Medication Tapering During Treatment With ECAP Controlled Closed-loop Spinal Cord Stimulation Trial Periods

Overview

This study is being conducted in patients who will receive a spinal cord stimulator. This device helps manage chronic neuropathic pain in the trunk and/or limbs. The patients will receive a spinal cord stimulator that is available, notified, and reimbursed in Belgium, which uses a special technology automatically adjusting the intensity of the stimulation. This is called a closed-loop system. The closed-loop system stimulates the Beta fibers in the spinal cord and simultaneously measures their response. Based on the measured response, the stimulation strength is automatically adjusted. In Belgium, after implant of the leads the effect must first be evalauted for 3 weeks before implanting the Internal Pulse Generator; this is called the trial period. Only if the trial is successful, the patients will receive a permanent implant. The primary goal of the study is to evaluate how different types of pain medication influence the neurophysiological response of the Beta fibers during spinal cord stimulation. Patients will be divided into three groups, based on the medication they are taking before receiving a spinal cord stimulator: * patients not taking any pain medication, * patients taking strong opioids, * patients taking anticonvulsant medication. As part of the study, patients will follow the normal clinical schedule. During visits, they will be asked questions about their pain, sleep, medication use, and activity. The study will end one month after the patient receives the permanent spinal cord stimulator implant.

Detailed description

Chronic neuropathic pain, particularly in patients with Persistent Spinal Pain Syndrome Type 2 (PSPS-T2, formerly FBSS), remains a major therapeutic challenge. Spinal cord stimulation (SCS) is an established therapy for patients with refractory pain. In Belgium, a 21-day trial period with an externalized epidural lead is mandatory before permanent implantation. During this trial, pain relief, improved sleep, increased activity, and reduction in pain medication intake must be documented in order to qualify for a permanent implant.

The Evoke™ Closed-Loop SCS system (Saluda Medical) is a CE-marked device used within its licensed indication in this study. This system uniquely records Evoked Compound Action Potentials (ECAPs) from the spinal cord, allowing continuous monitoring of neural activation. Closed-loop algorithms adjust stimulation output in real time based on measured ECAPs, thereby aiming to deliver consistent therapy within each patient's therapeutic window.

Recent pilot data and case reports have suggested that reductions in pain medication, particularly strong opioids and anticonvulsants, may alter spinal cord sensitivity to stimulation and ECAP parameters. A prospective pilot study performed at ZAS St. Augustinus Hospital (Belgium) demonstrated measurable changes in spinal cord sensitivity after medication reduction in patients implanted with the Evoke system. These findings suggest that medication tapering may influence neurophysiological responsiveness to SCS and highlight the importance of documenting this relationship systematically.

Study Design

This is a multicenter, open-label, prospective observational study enrolling 50 patients scheduled for SCS with the Evoke closed-loop system. Patients will be stratified into three groups according to baseline pain medication use:

1. Patients with no strong opioids or anticonvulsants (control group, n≈10). 2. Patients with monotherapy of strong opioids (n≈20). 3. Patients with monotherapy of anticonvulsants (n≈20).

All participants will undergo a 3-week trial with one or two epidural leads (T7 level). If the trial is successful, patients will proceed to permanent implantation of the closed-loop stimulator. Assessments will occur at baseline, each week during the trial, at permanent implantation, and one month post-implantation.

Assessments

* Documentation of medication use (daily/weekly via Belgian Pain Platform \[BPP\] and clinical verification). * Pain intensity (VAS), sleep, and activity (BPP). * Activation plots (relationship between current output and ECAP amplitude anchored by patient-reported thresholds and maximum tolerable perception). * Neurophysiological parameters: conduction velocity, chronaxie, rheobase.

Endpoints

* Primary endpoint: Effect of pain medication group on changes in spinal cord sensitivity to stimulation during the SCS trial, assessed through activation plots and medication intake. * Secondary endpoints: * Change in pain intensity (VAS) from baseline to post-trial. * Reduction in pain medication intake during the trial and one month after implantation. * Changes in sleep and activity. * Additional neurophysiological outcomes (conduction velocity, chronaxie, rheobase).

Duration of Participation Each patient will participate from baseline assessment through 1 month after permanent implantation. Study exit occurs either at completion or upon withdrawal (e.g., unsuccessful trial phase or medical reasons).

Burden and Risks The primary and secondary endpoints involve assessments routinely performed in SCS trials. Additional neurophysiological measurements (conduction velocity, chronaxie, rheobase) may add 5-10 minutes to a follow-up visit. Risks are limited to those normally associated with SCS implantation. There is no direct benefit to participants, but data may inform future research and optimization of medication management during SCS therapy.

Interventions

• Other Spinal Cord Stimulation with Evoke Closed-Loop System
  All participants will undergo trial stimulation with the Evoke ECAP-controlled closed-loop spinal cord stimulation system, followed by permanent implantation if the trial phase is successful. Neurophysiological parameters (activation plots, conduction velocity, chronaxie, rheobase) will be assessed alongside patient-reported outcomes (pain intensity, sleep, activity, medication use).

Primary outcome measures

• Spinal cord sensitivity expressed in ECAP amplitude (µV) as a function of the SCS stimulation amplitude (mA). [Time frame: From start of SCS trial (baseline) to 1 month after permanent implantation.]

Secondary outcome measures (3)

• Change in pain intensity measured using a 10 cm Visual Analog Scale (VAS) [Time frame: From start of SCS trial (baseline) to 1 month after permanent implantation.]
• Change in pain medication intake measured via Belgian Pain Platform (BPP) and clinical verification [Time frame: From start of SCS trial (baseline) to 1 month after permanent implantation.]
• Change in neurophysiological parameters such as conduction velocity (m/sec), rheobase (mA) and chronaxie (µs), measured using the Evoke system's neurophysiological assessment tools. [Time frame: From start of SCS trial (baseline) to 1 month after permanent implantation.]

Eligibility criteria

Inclusion criteria

• Patient deemed a suitable candidate for SCS and routinely scheduled to undergo a trial phase with the Evoke SCS system.
• Diagnosis of Persistent Spinal Pain Syndrome Type 2 (lower spine).
• Current medication use:
• No strong opioids or anticonvulsants, or other analgesics
• Monotherapy with a strong opioid, or
• Monotherapy with an anticonvulsant.
• Willing and able to provide written informed consent to participate, based on a voluntary agreement after a full explanation of the study.
• Age ≥ 18 years at the time of enrollment.
• Willing and able to comply with study requirements, procedures, and follow-up visits.

Exclusion criteria

• Evidence of an active disruptive psychological or psychiatric disorder, or other condition significant enough to impact pain perception, compliance with intervention, or ability to evaluate outcomes (as determined by the investigator in consultation with a clinical psychologist).
• Current diagnosis of a progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, rapidly progressive diabetic peripheral neuropathy, brain or spinal cord tumor, or severe/critical spinal stenosis.
• Current diagnosis or condition such as coagulation disorder, bleeding diathesis, platelet dysfunction, progressive peripheral vascular disease, or uncontrolled diabetes mellitus that presents excess risk for the procedure (as determined by the investigator).
• Active systemic or local infection.
• Pregnancy.
• Within 6 months prior to enrollment: significant untreated addiction to dependency-producing medications or a history of substance abuse (including alcohol or illicit drugs).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Belgium · 1 center

• Brai²n - ZAS Augustinus — Wilrijk

Publications

• Moens M, Crunelle CL, Putman K, Wuyts E, Bultinck F, Van Puyenbroeck H; PIANISSIMO consortium; Goudman L. Pain medication tapering for patients with Persistent Spinal Pain Syndrome Type II, treated with Spinal Cord Stimulation: A RCT-study protocol of the PIANISSIMO study. PLoS One. 2024 Aug 12;19(8):e0302842. doi: 10.1371/journal.pone.0302842. eCollection 2024. PMID 39133680
• Nissen M, Ikaheimo TM, Huttunen J, Leinonen V, Jyrkkanen HK, von Und Zu Fraunberg M. Higher Preimplantation Opioid Doses Associated With Long-Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome. Neuromodulation. 2021 Jan;24(1):102-111. doi: 10.1111/ner.13297. Epub 2020 Oct 19. PMID 33073907

Identifiers

NCT: NCT07413731 · Multicentric-ZAS-ECAP-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗