Sensory Improvements with 10kHz SCS: A Randomized Controlled Trial with Blinded, Disease Related Objective Assessments

Introduction: Painful diabetic neuropathy (PDN) is a common and debilitating complication of diabetes, characterized by chronic pain, diminished sensory function and loss of protective sensation[1,2]. The SENZA-PDN randomized controlled trial (RCT), demonstrated significant long-term improvements in lower-limb pain with high-frequency 10kHz spinal cord stimulation (10kHz-SCS), with two-thirds of participants also showing improvements in sensory function on clinical evaluation[3,4]. This novel observation provided the rationale for the PDN-Sensory RCT, from which the present report details the primary and secondary endpoint outcomes.

Methods: Participants with chronic, intractable lower limb pain due to PDN with a mean daily visual analogue scale (VAS) pain score ≥5 (0–10 scale), and sensory dysfunction based on the validated modified Toronto Clinical Neuropathy Scale (mTCNS) score > 5 (Table 1) were randomized 1:1 to Conservative medical management (CMM) alone or 10kHz-SCS in addition to CMM, with optional crossover at 6 months. The primary endpoint (pain relief) and the hierarchically tested secondary endpoints were evaluated at 6 months (Table 2). Secondary endpoints included the clinical assessment of sensory function (mTCNS), biopsy-based intra-epidermal nerve fiber density (IENFD) assessments, neuropathy related quality-of-life, functional status, and metabolic parameters. IENFD and mTCNS were allocation-blinded assessments. Institutional Review Board approval was obtained at 13 pain medicine and 3 endocrinologist clinical sites in the USA.

Results: Of the 143 participants enrolled, 91 were randomized, with comparable baseline characteristics across treatment groups (Table 1). In the CMM arm, 48 of the 50 patients randomized to CMM attended the 6-month assessments. In the 10kHz-SCS arm, 34 of the 41 randomized patients proceeded to trial making up the modified intent-to-treat group, and 29 received a permanent implant (Table 3). The primary pain-related endpoint (p < 0.001), all the secondary endpoints including sensory function improvement endpoints (p=0.014, Figure 1) and 7 hierarchical endpoints (Table 2) were met. In particular, in the 10kHz-SCS group, the nerve fiber density increased by 56%, a significant increase compared to the CMM group (p=0.027). The metabolic endpoints, weight and HbA1c did not significantly change.

Conclusion: This RCT is the first in the SCS field to demonstrate meaningful improvements in both pain and sensory function at 6 months with prespecified statistically tested endpoints. Notably, patients implanted with 10kHz-SCS demonstrated significant growth in IENFD in the lower calf. The clinical significance of these objective findings was supported by the substantial patient reported quality-of-life improvements in these 10khz-SCS treated patients suffering from PDN and sensory dysfunction.

Keyword 1: spinal cord stimulation

Keyword 2: 10 kHz SCS

Keyword 3: high-frequency SCS

Keyword 4: diabetic neuropathy

Keyword 5: painful diabetic neuropathy

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5. Argoff CE, Armstrong DG, Kagan ZB, Jaasma MJ, Bharara M, Bradley K, et al. Improvement in Protective Sensation: Clinical Evidence From a Randomized Controlled Trial for Treatment of Painful Diabetic Neuropathy With 10 kHz Spinal Cord Stimulation. J Diabetes Sci Technol. 2024:19322968231222271.

Funding: This study was sponsored by Nevro Corp.