Journal of Pain Research (Sep 2024)
Design of a Multicenter, Randomized Controlled Trial for the Treatment of Peripheral Neuropathic Pain (COMFORT Study) with a Micro-Implantable Pulse Generator
Abstract
John Hatheway,1 Alexander Perry Hersel,2 Jonathan Song,3 Mitchell P Engle,4 Genaro Gutierrez,5 Vishal Khemlani,6 Leonardo Kapural,7 Gregory Moore,8 Reginald Chinaedu Ajakwe,9 Drew M Trainor,10 Jennifer M Hah,11 Peter Staats,12 Paul Lynch,13 James Makous,14 Gary Heit15 ,† Shilpa Kottalgi,16 Mehul J Desai17 1Pain Management, Northwest Pain Care, Spokane, WA, USA; 2Pain Management, Pain Management and Injury Relief, Thousand Oaks, CA, USA; 3Pain Management, Arizona Pain Specialists, Scottsdale, AZ, USA; 4Pain Management, Institute of Precision Pain Medicine, Corpus Christi, TX, USA; 5Pain Management, Pain Specialists of America, Austin, TX, USA; 6Pain Management, Columbia Pain Management, Portland, OR, USA; 7Pain Management, Center for Clinical Research, Carolinas Pain Institute, Winston-Salem, NC, USA; 8Pain Management, Pacific Sports and Spine, Eugene, OR, USA; 9Pain Management, Comprehensive Spine & Pain, Burbank, CA, USA; 10Pain Management, Denver Spine and Pain Institute, Denver, CO, USA; 11Pain Management, Division of Pain Medicine, Stanford University, Palo Alto, CA, USA; 12Pain Management, Premier Pain Centers, Shrewsbury, NJ, USA; 13Pain Management, US Pain Care, Scottsdale, AZ, USA; 14Pain Management, Makous Research, LLC, Carlsbad, CA, USA; 15Department of Neurosurgery, Hue University of Medicine and Pharmacy, Hue, Vietnam; 16Clinical Affairs, Nalu Medical, Inc., Carlsbad, CA, USA; 17Pain Management, International Spine Pain & Performance Center, Washington, DC, USA†Gary Heit passed away in February 2023Correspondence: Shilpa Kottalgi, Nalu Medical, Inc., 2320 Faraday Ave, Carlsbad, CA, 92008, USA, Tel +1 858 344 1591, Fax +1 760 448 2379, Email [email protected]: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM).Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study.Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.Plain Language Summary: Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm3 in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (< 1.5 cm3 in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥ 50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months.Keywords: peripheral nerve stimulation, PNS, chronic pain, neuropathy, neuralgia, micro-IPG, battery-free
