(16) Beyond Pain: Evaluating 10kHz Spinal Cord Stimulation for Sensory Improvements in Painful Diabetic Neuropathy

Introduction: A recent randomized controlled trial (RCT) demonstrated profound pain relief in patients with painful diabetic neuropathy (PDN) treated with 10 kHz spinal cord stimulation (10kHz-SCS) to 24 months (SENZA-PDN).(1) While pain is often the primary motivation for patients to seek treatment for PDN, these patients often also suffer from reduced sensory function.(2) However, there are limited data supporting improvements in sensory function with conventional medical management(CMM).(3,4) A post-hoc analysis of sensory assessments in SENZA-PDN showed clinically significant sensory improvements in 10kHz-SCS-treated patients,(5) but a prospective study is needed. This RCT was designed to evaluate changes in pain and neurological function with 10kHz-SCS therapy compared to CMM in PDN patients.

Methods: Up to 236 patients will be enrolled at multiple sites across the US to obtain an estimated total of 118 patients randomized 1:1 into the two study groups, 10kHz-SCS and CMM, with an optional crossover at 6 months (Figure 1). The primary inclusion include diagnosis of diabetic peripheral neuropathy (DPN) with symptoms for greater than 12 months, refractory to at least two analgesic medications, lower-extremity pain >5cm on VAS, and modified Toronto Clinical Neuropathy Score (mTCNS) of >5. The primary endpoint, the proportion of patients in each group with ≥50% pain relief, and the secondary endpoints (Table 1) will be evaluated at 6 months. The first secondary endpoint will be the proportion of sensory improvement responders in each group, which is defined by ≥3-point improvement in mTCNS score, not including pain. The mTCNS is a sensitive and validated assessment for diagnosing DPN.(6,7) Patient reported outcomes include pain, neuropathy symptoms, disability, quality-of-life, sleep, and psychological aspects (Table 1). Neurological assessments will be performed by a blinded assessor to minimize bias.(8) A performance test (Timed-Up-and-Go) will provide an objective measure of functional improvement. Intraepidermal nerve fiber density (IENFD) tests at baseline, 6, and 12 months, will act as a biomarker for small fiber neuropathy.(9)

Results: Enrollment began on April 24, 2023 with 143 patients enrolled to date at 13 clinical sites. A case study shown in Figure 2 illustrates sensory improvements post-implant based on the mTCNS. In this study participant, the total mTCNS score was reduced by 82%, and the clinical assessment items by 70%.

Conclusion: This study is significant in that it will provide level 1 evidence to guide treatment options for patients with chronic, intractable PDN with moderate to severe sensory symptoms such as numbness, tingling, and weakness.