Closed-loop Spinal Cord Stimulation Research Articles

ID: 215794 ECAP-Based SCS for the Treatment of Chronic Pain: Crossover and 36-Month Evoke Study Outcomes

Utilization of objective neurophysiological measures to guide clinicians in providing optimal spinal cord stimulation (SCS) for chronic pain patients is a novel concept to neuromodulation. This clear and transparent mechanistic approach provides a better understanding to clinicians, patients, and payors allowing for proper evaluation of clinical outcomes. A novel SCS system delivers evoked-compound action potentials (ECAPs)-based therapy to 1) Guide programming and confirm activation of the intended target (i.e., ECAP-guided programming); and 2) Deliver closed-loop therapy to maintain accurate and consistent neural activation on every stimulus (i.e., ECAP-controlled closed-loop SCS). This therapy has now been studied in a 24-month double-blind randomized controlled trial (RCT) with self-selected crossover through 36 months. ECAP-based therapy enables real-time collection of continuous, objective, in-vivo neurophysiological data. This provides proper evaluation of the therapy and interpretation of the clinical outcomes, resulting in a level of evidence unmatched in neuromodulation.

ID: 222629 ECAP Study: Evaluating Holistic Response & Neurophysiology in Real-World Chronic Pain Using ECAP-Controlled Closed-Loop SCS

Chronic pain is a complex and personal experience influenced to varying degrees by biopsychosocial factors.1 Although several of these factors are commonly investigated in clinical trials, treatment response to interventions such as spinal cord stimulation (SCS) has often been based solely on reported reduction in pain intensity. As neurostimulation technology advances and substantial reductions in pain intensity are more commonly observed, the pursuit for a holistic responder beyond pain intensity alone has gained increased interest.2-5 This study aims to characterize the holistic treatment response of a real-world chronic pain population utilizing ECAP-controlled closed-loop SCS and explore the association with objective neurophysiological measurements.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis

ObjectiveSpinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. Materials and MethodsThe EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. ResultsThe mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved “good sleep quality” scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. “Normative” sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. ConclusionsECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. Clinical Trail RegistrationThe Clinicaltrials.gov registration number for the study is NCT02924129.

PO137 / #1010 EARLY RESULTS OF ECAP-CONTROLLED CLOSED-LOOP SPINAL CORD STIMULATION IN CRPS PATIENTS: E-POSTER VIEWING

Spinal cord stimulation (SCS) has proven to be an effective treatment for patients with Complex Regional Pain Syndrome (CRPS) [1]. ECAP-controlled (evoked compound action potential) closed-loop SCS measures and responds to neural activation of the spinal cord [2]. ECAP-controlled SCS has previously demonstrated to be more superior in pain relief in non-CRPS patients compared to traditional ‘open-loop’ SCS, with a more consistent neuronal activation of the spinal cord [2]. In this study, preliminary results of a data collection study in CRPS patients treated with closed-loop SCS (Data release) from the Erasmus Medical Centre in Rotterdam, the Netherlands, are presented (Netherlands Trial Register, ID: NL7889).

PO140 / #851 ECAP-CONTROLLED CLOSED-LOOP SCS THERAPY WITH A SINGLE LEAD FOR THE TREATMENT OF PERSISTENT SPINAL PAIN SYNDROME PATIENTS: E-POSTER VIEWING

Several articles have described the outcomes of a novel ECAP-controlled (evoked compound action potential) closed-loop SCS (spinal cord stimulation) system that aims to maintain spinal cord activation near a set target level and within a therapeutic window for each patient (1,2,3). For the aforementioned studies, patients have been implanted with two-percutaneous cylindrical leads. With the 6- to 12-months data presented on the poster we aim to evaluate the efficacy and (dis)advantages of single-lead placement with an ECAP-controlled closed-loop SCS system.

O071 / #840 ECAP-CONTROLLED CLOSED-LOOP SPINAL CORD STIMULATION IN A REAL-WORLD SETTING UNDER NORMAL CLINICAL USE: TRACK 4: CLINICAL USE OF SCS / DRG

Spinal cord stimulation (SCS) has proven to be an effective therapy for chronic pain [1], [2]. ECAP-controlled (evoked compound action potential) closed-loop SCS measures and responds to neural activation [3]. ECAP-controlled SCS has previously demonstrated more consistent activation of the spinal cord and correspondingly superior pain relief in patients as compared to traditional ‘open-loop’ SCS [3]. Here, preliminary results of the multi-center data collection study (Data release) from 5 centers in the Netherlands are presented (Netherlands Trial Register, ID: NL7889).

PO212 / #834 ECAP-CONTROLLED CLOSED-LOOP SCS-THERAPY FOR THE TREATMENT OF ANGINA PECTORIS PATIENTS: E-POSTER VIEWING

Spinal cord stimulation (SCS) is an established therapy option for the treatment for refractory Angina Pectoris-pain (AP) (1). Recently, a novel ECAP (evoked compound action potential)-controlled closed-loop SCS system has been introduced. This system aims to maintain spinal cord activation near a set target level and within a therapeutic window for each patient (2,3,4). With the data presented here, we aim to describe early results of closed-loop SCS-therapy for the treatment of AP.

PO139 / #779 ECAP-CONTROLLED CLOSED-LOOP 12 MONTH OUTCOMES OF A FBSS (FAILED BACK SURGERY SYNDROME) IN A SALVAGE CASE: E-POSTER VIEWING

Spinal cord stimulation (SCS) is an established treatment for patients suffering from chronic back and leg pain. A recent advance has been the development of ECAP-controlled Closed-Loop SCS, which uses real-time measurement of dorsal column fiber activation to maintain SCS therapy. The efficacy of ECAP-controlled closed-loop SCS has been previously published1,2. Herein is a case report for a patient that previously had an unsuccessful therapy with high-frequency waveform and has been subsequently implanted with an ECAP-controlled Closed-Loop SCS system.

PO138 / #777 ECAP-CONTROLLED CLOSED LOOP CONTROL SCS FOR TREATING CHRONIC UPPER-LIMB AND NECK PAIN IN A COMPLEX REGIONAL PAIN SYNDROME PATIENT: A CASE REPORT AT 24-MONTHS: E-POSTER VIEWING

Spinal cord stimulation (SCS) is an established treatment for patients suffering with complex regional pain syndrome (CRPS); however, cervical SCS poses challenges including extreme variability of electric fields. The efficacy of ECAP-controlled closed-loop SCS has been previously published1,2 for chronic pain of the trunk and lower limbs. Herein a case report for the first patient at 24-months from the Brighton Study (ACTRN12618001808235).

ID:16231 Clinical Feasibility of in Home, Closed-Loop Spinal Cord Stimulation With Differential Target Multiplexed Therapy

Recent advances in spinal cord stimulation (SCS) have focused on two highly novel areas; (1) differential target, multiplexed (DTM) SCS [1], which has demonstrated superior pain relief, and (2) the spinal Evoked Compound Action Potential (ECAP), a bioelectrical signal used as a measure of neural activation with closed-loop (CL) SCS systems to compensate for motion at the electrode-tissue interface [2]. Simultaneous application of both approaches may allow for a new generation of neural responsive SCS that blends a science-based methodology for pain management with real-time, CL control for biophysical variation. In this study, CL DTM-SCS was explored to assess feasibility in a home

ID:16038 Closed-Loop SCS: EVOKE RCT Long-Term & Secondary Outcomes at 12 Months

Evoked compound action potential (ECAP) recording provides an objective measure of dorsal column activation during spinal cord stimulation (SCS) and can assist in the programing of the SCS system. When using the ECAP in a closed-loop SCS (CL-SCS), the stimulation output is automatically adjusted to maintain a desired ECAP amplitude (i.e. consistent level of dorsal column activation). The efficacy of CL-SCS has been shown first in the Australian AVALON open-label study (ACTRN12615000713594) followed by the US EVOKE double-blinded RCT (NCT02924129).

ID:15791 Cyclical Variation in Spinal Evoked Compound Action Potentials: Considerations for Closed-Loop Spinal Cord Stimulation

The spinal cord exhibits rhythmic movement synchronous with physiologic events such as the cardiac and respiratory cycles.1 This movement results in variable spacing between spinal cord stimulation (SCS) leads and the cord, and subsequently, variable neural activation for both sub- and supra-perception SCS. Variability in neural activation may be quantified with the spinal Evoked Compound Action Potential (ECAP), a biosignal corresponding to the degree of group firing of dorsal column fibers in response to a stimulation pulse.

122 ECAP-Controlled Closed-Loop Spinal Cord Stimulation (CL SCS): Double-Blind, Randomized Trial for the Treatment of Chronic Pain – 24-Month Outcomes

INTRODUCTION: Evoked compound action potential (ECAP) recording provides an objective measure of spinal cord (SC) activation during SCS and can assist in programing of the SCS system. ECAP-controlled CL SCS, in which the stimulation output is automatically adjusted to maintain a desired ECAP amplitude, has been shown to provide effective pain relief in an open-label study (ACTRN12615000713594). METHODS: 134 subjects were enrolled and randomized after trial leads were implanted. The primary endpoint evaluated =50% reduction in overall back and leg pain measured by the Visual Analog Scale (VAS). Opioid usage and other patient-reported outcomes (PROs) including emotional/physical functioning, sleep quality, and quality of life were also collected. Additionally, objective neurophysiological data, including SC activation and time spent in the therapeutic range, were collected. RESULTS: Herein the Evoke Study Group reports the 24-month outcomes from this ongoing RCT. The proportion of implanted subjects with =50% overall back and leg pain reduction at 24 months was statistically superior in the CL vs. OL group (84.0% vs. 65.9% subjects, respectively; p = 0.040). Long-term improvements in all other PROs, including POMS, ODI, PSQI, EQ-5D-5L, and SF-12, were also demonstrated. Opioids were reduced or eliminated in 66.7% (CL) and 60.9% (OL), respectively. The most frequent level of SC activation was three times greater for CL (median ECAP Amplitude: 22.5 µV CL vs. 7.5 µV OL). SC activation was better maintained within the therapeutic range with CL (median: 93.9% CL vs. 46.1% OL). There were no differences in the safety profiles between treatment groups, and the type, nature, and severity of adverse events were similar to other SCS studies. CONCLUSION: In this ongoing study, ECAP-controlled CL SCS provided statistically superior pain relief and greater improvement in other PROs compared with OL SCS at 24 months. CL delivered greater levels of SC activation and better maintained SC activation in the subject’s therapeutic range.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain

Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system. To determine whether ECAP-controlled, closed-loop SCS is associated with better outcomes compared with fixed-output, open-loop SCS at 24 months following implant. The Evoke study was a double-blind, randomized, controlled, parallel arm clinical trial with 36 months of follow-up. Participants were enrolled from February 2017 to 2018, and the study was conducted at 13 US investigation sites. SCS candidates with chronic, intractable back and leg pain refractory to conservative therapy, who consented, were screened. Key eligibility criteria included overall, back, and leg pain visual analog scale score of 60 mm or more; Oswestry Disability Index score of 41 to 80; stable pain medications; and no previous SCS. Analysis took place from October 2020 to April 2021. ECAP-controlled, closed-loop SCS was compared with fixed-output, open-loop SCS. Reported here are the 24-month outcomes of the trial, which include all randomized patients in the primary and safety analyses. The primary outcome was a reduction of 50% or more in overall back and leg pain assessed at 3 and 12 months (previously published). Of 134 randomized patients, 65 (48.5%) were female and the mean (SD) age was 55.2 (10.6) years. At 24 months, significantly more closed-loop than open-loop patients were responders (≥50% reduction) in overall pain (53 of 67 [79.1%] in the closed-loop group; 36 of 67 [53.7%] in the open-loop group; difference, 25.4% [95% CI, 10.0%-40.8%]; P = .001). There was no difference in safety profiles between groups (difference in rate of study-related adverse events: 6.0 [95% CI, -7.8 to 19.7]). Improvements were also observed in health-related quality of life, physical and emotional functioning, and sleep, in parallel with opioid reduction or elimination. Objective neurophysiological measurements substantiated the clinical outcomes and provided evidence of activation of inhibitory pain mechanisms. ECAP-controlled, closed-loop SCS, which elicited a more consistent neural response, was associated with sustained superior pain relief at 24 months, consistent with the 3- and 12-month outcomes.

A New Direction for Closed-Loop Spinal Cord Stimulation: Combining Contemporary Therapy Paradigms with Evoked Compound Action Potential Sensing.

Spinal cord stimulation (SCS) utilizes the delivery of mild electrical pulses via epidural electrodes placed on the dorsal side of the spinal cord, typically to treat chronic pain. The first clinical use of SCS involved the delivery of paresthesia inducing, low-frequency waveforms to the neural targets corresponding to the painful areas. Contemporary SCS therapies now leverage novel therapeutic pathways to limit paresthesia and deliver superior clinical outcomes. Historically, SCS has largely been delivered with fixed stimulation parameters. This approach, referred to as open-loop (OL) SCS, does not account for the fluctuations in spacing—driven by postural changes and activity—between the electrodes and the cord. These fluctuations result in variability in the delivered dose and the volume of tissue activation (VTA) that manifests with each stimulation pulse. Inconsistent dosing may lead to suboptimal therapeutic efficacy and durability. To address this clinical need, closed-loop (CL) SCS systems have been developed to automatically adjust stimulation parameters to compensate for this variability. The evoked compound action potential (ECAP), a biopotential generated by the synchronous activation of dorsal column fibers, is indicative of the VTA resulting from the stimulation pulse. The ECAP may be utilized as a control signal in CL SCS systems to adjust stimulation parameters to reduce variability in the ECAP, and in turn, variability in the VTA. While investigational CL SCS systems with ECAP sensing have so far focused solely on managing paresthesia-based SCS, such systems must also incorporate the stimulation approaches that now define the contemporary clinical practice of SCS. Accordingly, we describe here a flexible, next-generation framework for neural responsive SCS that blends science-based methodologies for pain management with real-time CL control for biophysical variation. We conclude with a clinical example of such a system and the associated performance characteristics.

Sustained Long-Term Outcomes With Closed-Loop Spinal Cord Stimulation: 12-Month Results of the Prospective, Multicenter, Open-Label Avalon Study

Russo, Marc MBBS, DA; Brooker, Charles MBChB; Cousins, Michael J MD, DSc; Taylor, Nathan MBBS; Boesel, Tillman MBBS; Sullivan, Richard MBChB; Holford, Lewis MBChB; Hanson, Erin MPH; Gmel, Gerrit Eduard PhD; Shariati, Nastaran Hesam PhD; Poree, Lawrence MD, PhD; Parker, John PhD Author Information

Spinal Cord Stimulation as Treatment for Cancer and Chemotherapy-Induced Pain.

Neuropathic pain is a rampant disease exacting a significant toll on patients, providers, and health care systems around the globe. Neuromodulation has been successfully employed to treat many indications including failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), phantom limb pain (PLP), radiculopathies, and intractable pelvic pain, among many others. Recent studies have also demonstrated efficacy for cancer-related pain and chemotherapy induced neuropathy with these techniques. Spinal cord stimulation (SCS) is the most commonly employed technique and involves implantation of percutaneous or paddle leads targeting the dorsal columns of the spinal cord with the goal of disrupting the pain signals traveling to the brain. Tonic, high frequency, and burst waveforms have all been shown to reduce pain and disability in chronic pain patients. Closed-loop SCS systems that automatically adjust stimulation parameters based on feedback (such as evoked compound action potentials) are becoming increasingly used to help ease the burden placed on patients to adjust their programming to their pain and position. Additionally, dorsal root ganglion stimulation (DRGS) is a newer technique that allows for dermatomal coverage especially in patients with pain in up to two dermatomes. Regardless of the technique chosen, neuromodulation has been shown to be cost-effective and efficacious and should be given full consideration in patients with chronic pain conditions.

Closed Loop Spinal Cord Stimulation

Closed Loop Spinal Cord Stimulation

ECAP-Controlled Closed-Loop Spinal Cord Stimulation Efficacy and Opioid Reduction Over 24-Months: Final Results of the Prospective, Multicenter, Open-Label Avalon Study.

IntroductionChronic pain is a major public health concern, as is the associated use of opioid medications, highlighting the importance of alternative treatments, such as spinal cord stimulation (SCS). Here, we present the final 24‐month results of the Avalon study, which investigated the use of the first closed‐loop SCS system in patients with chronic pain. The system measures the evoked compound action potentials (ECAPs) elicited by each stimulus pulse and drives a feedback loop to maintain the ECAP amplitude near constant.MethodsFifty patients were implanted with the Evoke system (Saluda Medical) and followed over 24‐months. Pain, quality of life (QOL), function, sleep, and medication use were collected at baseline and each scheduled visit. ECAP amplitudes and programming adjustments were also monitored.ResultsAt 24 months, responder rates (≥ 50% pain reduction) and high responder rates (≥ 80% pain reduction) for overall pain were 89.5% and 68.4%, respectively, the latter up from 42.2% at 3 months. Significant improvements from baseline were observed in QOL, function, and sleep over the 24 months, including ≥ 80% experiencing a minimally important difference in QOL and > 50% experiencing a clinically significant improvement in sleep. At 24 months, 82.8% of patients with baseline opioid use eliminated or reduced their opioid intake. Over the course of the study, reprogramming need fell to an average of less than once a year.ConclusionOver a 24‐month period, the Evoke closed‐loop SCS maintained its therapeutic efficacy despite a marked reduction in opioid use and steady decrease in the need for reprogramming.

Sustained Long-Term Outcomes With Closed-Loop Spinal Cord Stimulation: 12-Month Results of the Prospective, Multicenter, Open-Label Avalon Study.

BACKGROUNDSpinal cord stimulation (SCS) activates the dorsal column fibers using electrical stimuli. Current SCS systems function in fixed-output mode, delivering the same stimulus regardless of spinal cord (SC) activation.OBJECTIVETo present long-term outcomes of a novel closed-loop SCS system that aims to maintain the SC activation near a set target level and within a therapeutic window for each patient. SC activation is measured through the evoked compound action potential (ECAP) generated by each stimulus pulse.METHODSFifty patients with lower back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (visual analog scale), quality of life, function, sleep, and medication use were collected at baseline and at each visit. SC activation levels were reported in summary statistics. The therapeutic window for each individual patient was defined as the range of ECAP amplitudes between sensation threshold and uncomfortably strong stimulation.RESULTSAt 12 mo, the proportion of patients with ≥50% relief was 76.9% (back), 79.3% (leg), and 81.4% (overall), and the proportion with ≥80% pain relief was 56.4% (back), 58.6% (leg), and 53.5% (overall). Patients spent a median of 84.9% of their time with stimulation in their therapeutic window, and 68.8% (22/32) eliminated or reduced their opioid intake. Statistically significant improvements in secondary outcomes were observed.CONCLUSIONThe majority of patients experienced more than 80% pain relief with stable SC activation, as measured by ECAP amplitude at 12 mo, providing evidence for the long-term effectiveness of the Evoke closed-loop SCS system.