Nociceptive Chronic Low Back Pain Treated by Ultra Low Frequency Neuromodulation: First-in-human Primary Endpoint Results

Introduction: Chronic low back pain (CLBP) continues to be a prevalent and disabling condition worldwide. Spinal cord stimulation (SCS), commercially available since the 1980s, is effective for neuropathic pain conditions; however, many patients with CLBP have predominant somatic or nociceptive pain and are not well treated with current SCS devices. Early data for Ultra Low Frequency (ULF™) SCS suggest a novel mechanism of action that effectively treats nociceptive CLBP (1). This first-in-human study evaluated the safety and effectiveness of ULF neuromodulation.

Methods: This prospective, single-arm, multicenter clinical trial enrolled subjects with CLBP, with or without leg pain, and treated them with ULF SCS (Presidio Medical, San Mateo, CA USA).
Eligible participants had CLBP rated a minimum of 60 out of 100mm on a visual analog scale (VAS) with symptoms refractory to conservative therapy for at least 3 months and were medically suitable to undergo SCS procedures. Outcome measures evaluated pain via a 7-day VAS diary, disability, depression, sleep, health-related quality of life, and subject satisfaction. The primary endpoint was the proportion of back pain responders at 3-month follow-up, defined as those with ≥50% reduction from baseline.

Results: A total of 50 participants received ULF SCS device implants, including 29 (58%) females and 21 (42%) males. The median age was 64.6 years (range:27.5-91.3) with average BMI of 30.2kg/m2 (SD:5.2) and an average 21-year history of CLBP (range:1-70). Pain was characterized by clinical evaluation as predominantly nociceptive for 28 (56%) participants, predominantly neuropathic for 6 (12%), and the remaining 16 (32%) had significant contributions of each. Participants had an average baseline back pain VAS of 75mm (SD:8.7) and Oswestry Disability Index (ODI) score of 44% (SD:12.6). At 3 months, 83.8% (95% CI:73.5-94.1%) of participants were back pain responders which met the definition of primary endpoint success. Participants experienced an average 72% improvement in back pain with VAS of 22mm (SD:20.9). Average ODI score was 22% (SD:14.0) and participants noted improvement across the array of outcomes collected. There were 2 serious adverse events related to surgical procedures and none related to ULF device or therapy. Both procedure-related events resolved without sequelae.

Conclusion: Nociceptive CLBP has long been undertreated and there is a dearth of SCS research targeting this patient group(2). Thus, treatment guideline recommendations and payer coverage specifically endorse SCS to treat neuropathic conditions and not predominant nociceptive pain. ULF neuromodulation safely and effectively treats nociceptive CLBP via a unique mechanism of neural inhibition.