20 - 10 kHz Spinal Cord Stimulation for Treatment of Painful Diabetic Neuropathy - A Multicenter Randomized Controlled Trial

Erika Petersen¹, Thomas Stauss², James Scowcroft³, Elizabeth Brooks⁴, Judith White⁵, Shawn Sills⁶, Kasra Amirdelfan⁷, Maged Guirguis⁸, Jijun Xu⁹, Cong Yu¹⁰, Ali Nairizi¹¹, Denis Patterson¹¹, Vincent Galan¹², Richard Bundschu¹³, Neel Mehta¹⁴, Dawood Sayed¹⁵, Shivanand Lad¹⁶, David DiBenedetto¹⁷, Khalid Sethi¹⁸, Paul Wu¹⁹, Charles Argoff²⁰, Christian Nasr⁹, Rod Taylor²¹, Jeyakumar Subbaroyan⁴, Bradford Gliner⁴, David Caraway4, Nagy Mekhail⁹

¹University of Arkansas for Medical Sciences, Little Rock, USA. ²Advanced Pain Management, Greenfield, USA. ³Pain Management Associates, Lee's Summit, USA. ⁴Nevro Corp., Redwood City, USA. ⁵AES Compass Orlando, Orlando, USA. ⁶Touchstone Interventional Pain Center, Medford, USA. ⁷IPM Medical Group, Walnut Creek, USA. ⁸Ochsner Health System, New Orleans, USA. ⁹Cleveland Clinic, Cleveland, USA. ¹⁰Swedish Medical Center, Seattle, USA. ¹¹Nevada Advanced Pain Specialists, Reno, USA. ¹²Pain Care, Stockbridge, USA. ¹³Coastal Orthopedics and Sports Medicine, Bradenton, USA. ¹⁴Weill Cornell Medical College, New York, USA. ¹⁵University of Kansas Medical Center, Kansas City, USA. ¹⁶Duke University, Durham, USA. ¹⁷Boston PainCare, Waltham, USA. ¹⁸United Health Services, Johnson City, USA. ¹⁹Holy Cross Hospital, Fort Lauderdale, USA. ²⁰Albany Medical Center, Albany, USA. ²¹University of Glasgow, Glasgow, United Kingdom

Purpose
The Centers for Disease Control and Prevention (CDC) estimates there are 34.2 million persons with diabetes and 88.0 million with prediabetes in the US.¹ Approximately 20% will develop painful diabetic neuropathy (PDN),² a chronic pain condition significantly impacting health-related quality of life. Neither pharmacological treatments nor low-frequency spinal cord stimulation (SCS) provides long-term relief for many of these patients;^3-6 however, preliminary data suggest 10 kHz SCS relieves pain and improves sensory deficits.⁷
Methods
A prospective, multicenter, randomized controlled trial (SENZA-PDN) with 216 subjects assigned 1:1 to 10 kHz SCS (Nevro Corp.) combined with conventional medical management (CMM) or CMM alone. Key inclusion criteria: PDN symptoms present for ≥12 months that are refractory to medications, lower limb pain ≥ 5 cm (on 0-10 cm visual analog scale [VAS]), and appropriate candidate for SCS. Key exclusion criteria: hemoglobin A1c > 10%, daily opioid dosage > 120 mg morphine equivalents, and upper limb pain ≥ 3 cm. Outcomes include pain, neurological function, health-related quality of life, sleep, satisfaction, and cost-effectiveness. Follow-up will last 24 months.
Results
Screening 430 candidates resulted in 113 subjects randomized to 10 kHz SCS+CMM and 103 to CMM alone. Treatment arms were well matched across a variety of baseline characteristics, including hemoglobin A1c, and duration of diabetes and peripheral neuropathy. There were no reported study-related adverse events (AEs) for the CMM group and 16 study-related AEs reported in the 10 kHz SCS+CMM group up to 3 months. There were 2 procedure-related infections in the 10 kHz SCS+CMM group, representing a 1.8% infection rate.
Intention-to-treat analysis revealed 5% CMM and 79% 10 kHz SCS+CMM subjects met the primary endpoint (p< 0.001). Lower limb pain scores (mean ± SEM) in the CMM group were 7.0 ± 0.2 cm at baseline and 6.5 ± 0.2 cm at 3-month follow-up. In the 10 kHz SCS+CMM group, lower limb pain scores were 7.6 ± 0.2 cm at baseline and 1.7 ± 0.2 cm at 3 months. Analysis of the per-protocol population revealed 7% of the CMM group experienced pain relief ≥ 50% versus 89% of the 10 kHz SCS+CMM group. Investigator-assessed sensory improvements were observed in 7% of the CMM group, while 72% of the 10 kHz SCS+CMM group had such improvement compared to baseline. Similar differences between the treatment groups were observed across several quality of life and functional measures.
Conclusions
The SENZA-PDN study is the largest RCT to date of SCS management of PDN patients and will help inform the place of 10 kHz SCS in the PDN treatment continuum. The primary endpoint was met with a significant proportion of subjects responding to 10 kHz SCS. These early results are encouraging for PDN patients with symptoms refractory to conventional care.