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INTRODUCTION: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. METHODS: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. RESULTS: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7-99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1-1.4) and dose accuracy of 4.4 µV (0.0-7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). CONCLUSIONS: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient-device interaction metrics. CLINICAL TRIAL REGISTRATION: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.
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BACKGROUND: Preclinical models of spinal cord stimulation (SCS) are lacking objective measurements to inform translationally applicable SCS parameters. The evoked compound action potential (ECAP) represents a measure of dorsal column fiber activation. This measure approximates the onset of SCS-induced sensations in humans and provides effective analgesia when used with ECAP-controlled closed-loop (CL)-SCS systems. Therefore, ECAPs may provide an objective surrogate for SCS dose in preclinical models that may support better understanding of SCS mechanisms and further translations to the clinics. This study assessed, for the first time, the feasibility of recording ECAPs and applying ECAP-controlled CL-SCS in freely behaving rats subjected to an experimental model of neuropathic pain. METHODS: Adult male Sprague-Dawley rats (200-300 g) were subjected to spared nerve injury (SNI). A custom-made six-contact lead was implanted epidurally covering T11-L3, as confirmed by computed tomography or X-ray. A specially designed multi-channel system was used to record ECAPs and to apply ECAP-controlled CL-SCS for 30 min at 50 Hz 200 µs. The responses of dorsal column fibers to SCS were characterized and sensitivity towards mechanical and cold stimuli were assessed to determine analgesic effects from ECAP-controlled CL-SCS. Comparisons between SNI rats and their controls as well as between stimulation parameters were made using omnibus analysis of variance (ANOVA) tests and t-tests. RESULTS: The recorded ECAPs showed the characteristic triphasic morphology and the ECAP amplitude (mV) increased as higher currents (mA) were applied in both SNI animals and controls (SNI SCS-ON and sham SCS-ON). Importantly, the use of ECAP-based SCS dose, implemented in ECAP-controlled CL-SCS, significantly reduced mechanical and cold hypersensitivity in SNI SCS-ON animals through the constant and controlled activation of dorsal column fibers. An analysis of conduction velocities of the evoked signals confirmed the involvement of large, myelinated fibers. CONCLUSIONS: The use of ECAP-based SCS dose implemented in ECAP-controlled CL-SCS produced analgesia in animals subjected to an experimental model of neuropathic pain. This approach may offer a better method for translating SCS parameters between species that will improve understanding of the mechanisms of SCS action to further advance future clinical applications.
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INTRODUCTION: A novel closed-loop spinal cord stimulation (SCS) system has recently been approved for use which records evoked compound action potentials (ECAPs) from the spinal cord and utilizes these recordings to automatically adjust the stimulation strength in real time. It automatically compensates for fluctuations in distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a determined target level. This data collection was principally designed to evaluate the performance of this first closed-loop SCS system in a 'real-world' setting under normal conditions of use in a single European center. METHODS: In this prospective, single-center observational data collection, 22 patients were recruited at the outpatient pain clinic of the St. Antonius Hospital. All candidates were suffering from chronic pain in the trunk and/or limbs due to PSPS type 2 (persistent spinal pain syndrome). As standard of care, follow-up visits were completed at 3 months, 6 months, and 12 months post-device activation. Patient-reported outcome data (pain intensity, patient satisfaction) and electrophysiological and device data (ECAP amplitude, conduction velocity, current output, pulse width, frequency, usage), and patient interaction with their controller were collected at baseline and during standard of care follow-up visits. RESULTS: Significant decreases in pain intensity for overall back or leg pain scores (verbal numerical rating score = VNRS) were observed between baseline [mean ± SEM (standard error of the mean); n = 22; 8.4 ± 0.2)], 3 months (n = 12; 1.9 ± 0.5), 6 months (n = 16; 2.6 ± 0.5), and 12 months (n = 20; 2.0 ± 0.5), with 85.0% of the patients being satisfied at 12 months. Additionally, no significant differences in average pain relief at 3 months and 12 months between the real-world data (77.2%; 76.8%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies were observed. CONCLUSIONS: These initial 'real-world' data on ECAP-controlled, closed-loop SCS in a real-world clinical setting appear to be promising, as they provide novel insights of the beneficial effect of ECAP-controlled, closed-loop SCS in a real-world setting. The presented results demonstrate a noteworthy maintenance of pain relief over 12 months and corroborate the outcomes observed in the AVALON prospective, multicenter, single-arm study and the EVOKE double-blind, multicenter, randomized controlled trial. TRIAL REGISTRATION: The data collection is registered on the International Clinical Trials Registry Platform (Trial NL7889).