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

Abstract

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.

Keywords: CMM, conventional medical management; DN4, Douleur Neuropathique; DSPN, diabetic sensorimotor peripheral neuropathy; EQ-5D-5L, EuroQol 5-Dimension 5-Level questionnaire; HRQoL, health-related quality of life; HbA1c, hemoglobin A1c; IPG, implantable pulse generator; NNT, number needed to treat; PDN, painful diabetic neuropathy; RCT, randomized controlled trial; SCS, spinal cord stimulation; VAS, visual analog scale.

© 2022 The Authors.

Figures

Figure 1

Disposition of all participants through 12 months. ∗Trial SCS was discontinued for 2 patients: 1 patient removed trial leads at home, whereas the other patient had a significant lead migration. †Participants without the 3-month primary end point assessment were included only in the SG for AE reporting for the remainder of the study; other outcomes were not aggregated for analysis. AE, adverse event; CMM, conventional medical management; f/u, follow-up; SCS, spinal cord stimulation; SG, safety group; WC, withdrew consent.

Figure 2

A, Individual pain responses among all 10-kHz SCS implanted participants (n=142) at 12 months. Each line represents the improvement in a single participant’s lower limb pain score relative to the baseline. Treatment responders (n=121) are those with at least 50% pain relief, shown in blue, with nonresponders (n=21) shown in orange. The average pain relief among all implanted participants at 12 months was 74%. B, The 5-level EQ-5D-5L measures health-related quality of life. Participants rate 5 items each with 5 levels of response that are converted to an index value on the basis of the US population norms, ranging from −0.109 (a state worse than death) to 1.000 (perfect health). The average scores are plotted over time for the 10-kHz SCS+CMM group participants (n=84, blue line, open squares) and CMM group participants who crossover after 6 months (n=57, orange line preimplant, blue line postimplant, open circles). C, The PSQ-3 evaluates the impact of pain on falling asleep and staying asleep with three 10-cm VASs, where 0 cm means “never” and 10 cm means “always.” The average scores are plotted over time for the 10-kHz SCS+CMM group participants (n=84, blue line, open squares) and CMM group participants who crossover after 6 months (n=58, orange line preimplant, blue line postimplant, open circles). D, The BPI-DPN scale has been validated in patients with PDN and assesses pain interference with activity, mood, and activities of daily living via 7 items on a scale of 0 (does not interfere) to 10 (completely interferes). The average scores are plotted over time for the 10-kHz SCS+CMM group participants (n=84, blue line, open squares) and CMM group participants who crossover after 6 months (n=57, orange line preimplant, blue line postimplant, open circles). E, The GAF scale requires clinician assessment of the patient’s mental health and well-being on a scale of 1 (persistent danger to oneself or others OR unable to maintain personal hygiene OR serious suicidality) to 100 (superior functioning in a wide range of activities/no symptoms). The average scores are shown over time for the 10-kHz SCS+CMM group participants (n=80, orange bar preimplant, blue bars postimplant) and CMM group participants who crossover after 6 months (n=56, orange bars preimplant, blue bars postimplant). F, The participants rated their satisfaction with treatment on a 5-point Likert scale ranging from “very dissatisfied” to “very satisfied” at 12 months. Proportions are shown for all implanted participants (n=142). Error bars: 95% CI, ∗P<.05, ∗∗P<.01, ∗∗∗P<.001. BPI-DPN, Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy; CMM, conventional medical management; EQ-5D-5L, EuroQol 5-dimensional questionnaire; GAF, Global Assessment of Functioning; PDN, painful diabetic neuropathy; PSQ-3, Pain and Sleep Questionnaire 3-Item Index; SCS, spinal cord stimulation; VAS, visual analog scale.