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 cmor 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 A(1c) (HbA(1c)) of 10% or less, daily morphine equivalents of 120mg 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 pointwas 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) agewas 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathywere 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 populationwasmet by 5 of 94 patients in theCMM group (5%) and 75 of 95 patients in the 10-kHz SCS plusCMMgroup (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 plusCMMgroup (2%). For theCMMgroup, the mean pain VAS scorewas 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 CMMgroup, the mean pain VAS scorewas 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 theCMMgroup (3%) and 52 of 84 in the 10-kHz SCS plusCMMgroup (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.