Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.

AIMS: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN). METHODS: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding. RESULTS: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection. CONCLUSIONS: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN. TRIAL REGISTRATION: ClincalTrials.gov Identifier, NCT03228420.

High-Frequency 10-kHz Spinal Cord Stimulation Improves Health-Related Quality of Life in Patients With Refractory Painful Diabetic Neuropathy: 12-Month Results From a Randomized Controlled Trial.

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were "satisfied" or "very satisfied" with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420.

A Real-World Analysis of High-Frequency 10 kHz Spinal Cord Stimulation for the Treatment of Painful Diabetic Peripheral Neuropathy.

BACKGROUND: Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited. METHOD: This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device. Available data were extracted from a commercial database. RESULTS: In total 89 patients consented to being included in the analysis. Sixty-one percent (54/89) of participants were male and the average age was 64.4 years (SD = 9.1). Most patients (78.7%, 70/89) identified pain primarily in their feet or legs bilaterally. At the last assessment, 79.5% (58/73) of patients were treatment responders, defined as having at least 50% patient-reported pain relief from baseline. The average time of follow-up was 21.8 months (range: 4.3 to 46.3 months). A majority of patients reported improvements in sleep and overall function relative to their baseline. CONCLUSIONS: This real-world study in typical clinical practices found 10 kHz SCS provided meaningful pain relief for a substantial proportion of patients refractory to current pDPN management, similar to published literature. This patient population has tremendous unmet needs and this study helps demonstrate the potential for 10 kHz SCS to provide an alternative pain management approach.

Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. Interventions: Implanted medical device delivering 10-kHz SCS. Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. Trial Registration: ClincalTrials.gov Identifier: NCT03228420.

10 kHz High-Frequency Spinal Cord Stimulation for Chronic Thoracic Pain: A Multicenter Case Series and a Guide for Optimal Anatomic Lead Placement.

BACKGROUND: Surgical options for thoracic pain are limited and carry significant risk and morbidity. Spinal cord stimulation has the potential to be used for treatment of thoracic pain, as it has been useful for treating multiple types of chronic pain. Conventional tonic stimulation is limited in the treatment of thoracic pain, as it can produce paresthesia that is difficult to localize. Conversely, high-frequency spinal cord stimulation (HF-SCS) does not activate dorsal column A Beta fibers and does not produce paresthesia, and thus may be more beneficial in treating thoracic back pain not manageable with tonic stimulation. OBJECTIVES: To evaluate (1) the efficacy of 10 kHz HF-SCS for patients with chronic thoracic pain; and (2) appropriate paresthesia-free lead placement and programming targets for 10 kHz HF-SCS for patients with chronic thoracic pain. STUDY DESIGN: Retrospective case series. SETTING: Multisite academic medical center or pain clinic. METHODS: A retrospective chart review was performed on 19 patients with thoracic back pain who underwent HF-SCS implantation. These patients had lead placement and stimulation between the T1-T6 vertebral levels. Outcome measures collected include location of device implant, stimulation settings, and pain scores at baseline, end of trial, and 1, 6, and 12 months postimplant. Follow-up phone calls collected information on if the patient reported functional improvement, improved sleep, or decreased pain medication usage. A Wilcoxon signed-rank test compared differences in mean pain scores across time points. RESULTS: Significantly decreased Visual Analog Scale scores were observed with 17/19 (89.5%) patients demonstrating response to therapy (> 50% reduction in pain scores). These results were sustained relative to baseline at 1, 6, and 12 months postimplant, depending on length of follow-up. Many patients also reported functional improvement (17/19), improved sleep (14/19), and reduction in use of pain medications after implantation (9/19). A total of 15/19 patients reported best relief when contacts over T1 or T2 vertebrae were used for stimulation. LIMITATIONS: This study is limited by its retrospective design. Additionally, including documentation from multiple sites may be prone to selection and abstraction bias. Data were also not available for all patients at all time points. CONCLUSIONS: HF-SCS may be a viable option for significant, long-lasting pain relief for thoracic back pain. There may also be evidence for anatomically based lead placement and programming for thoracic back pain. Randomized, controlled trials with extended follow-up are needed to further evaluate this therapy. KEY WORDS: Thoracic pain, back pain, spinal cord stimulation, high frequency, 10 kHz.

Treatment of painful polyneuropathies of diabetic and other origins with 10 kHz SCS: a case series.

Painful diabetic polyneuropathy (PDPN) and painful polyneuropathies of other origins are associated with significant personal and societal burdens with treatments limited to symptomatic management. Treatment options include antidepressants, gamma-aminobutyric acid (GABA) analogs, opioids, and topical analgesics, which are intended to alleviate pain and symptoms of neuropathy, but limited data are available on their efficacy. Paresthesia-based low-frequency spinal cord stimulation (LF-SCS) is considered a last-resort treatment modality for PDPN patients. In a large-scale RCT of neuropathic low back and leg pain, high-frequency SCS at 10 kHz (10 kHz SCS) was shown to provide superior pain relief that is not dependent on paresthesia and a higher responder rate than LF SCS. This retrospective case series includes data from six patients with painful peripheral neuropathies, including PDPN, idiopathic polyneuropathy, and chronic inflammatory demyelinating polyneuropathy, who were candidates for 10 kHz SCS in routine commercial practice. All patients reported a reduction in verbal numerical rating scale (VNRS) pain score at last follow-up (2.7 ± 0.9) compared with baseline (7.0 ± 0.9). Out of five patients with information available at last follow-up, two were completely off their pain medications and two reduced their dose by over 40%. Similarly, at last follow-up, three out of five patients reported sensory improvement in their lower limbs. In conclusion, 10 kHz SCS treatment resulted in significant pain relief in all the patients, decreased reliance on pain medication, and improved lower limb sensory function in the majority of patients.